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CD27-related lymphoproliferative and immune disorder

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of CD27-related lymphoproliferative and immune disorder. Core disease mechani...

2026-04-19
Asta MONDO:0014054 Model: Asta Scientific Corpus Retrieval 20 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of CD27-related lymphoproliferative and immune disorder. Core disease mechani...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] Germline STAT3 gain-of-function mutations in primary immunodeficiency: Impact on the cellular and clinical phenotype

  • Authors: Laura Faletti, S. Ehl, Maximilian Heeg
  • Year: 2021
  • Venue: Biomedical Journal
  • URL: https://www.semanticscholar.org/paper/21f376f67897eb5eb8f262a2cd0a13850bd1144a
  • DOI: 10.1016/j.bj.2021.03.003
  • PMID: 34366294
  • PMCID: 8514798
  • Citations: 32
  • Influential citations: 2
  • Summary: The current understanding of the disease is summarized and the clinical phenotype, diagnostic approach, cellular and molecular effects of STAT3 GOF mutations and therapeutic concepts for these patients are discussed.
  • Evidence snippets:
  • Snippet 1 (score: 0.483) > unraveling the molecular and cellular mechanisms underlying this disease. In this review, we summarize our current understanding of the disease and discuss the clinical phenotype, diagnostic approach, cellular and molecular effects of STAT3 GOF mutations and therapeutic concepts for these patients. > Control of immune cell activation is critical to restore immune homeostasis after resolution of infections and to prevent immunopathology including autoimmune diseases. Uncontrolled expansion of immune cells is a hallmark feature of benign lymphoproliferation manifesting as lymphadenopathy and/or splenomegaly and of immune-cell derived malignancies. The combination of lymphoproliferation and autoimmunity or immunopathology, variably associated with increased infection susceptibility, is characteristic for a group of inborn errors of immunity that can be summarized as autoimmune-lymphoproliferative primary immunodeficiencies (AL-PID). In recent years, tremendous progress has been made in understanding the genetic and molecular mechanisms underlying this spectrum of diseases. Mutations in the FAS pathway were the first genetic variants identified to cause autoimmune-lymphoproliferative syndromes (ALPS) in the 1990s [1]. However, recent advances in genetics have allowed the discovery of defects in many other pathways that can lead to ALPS-like clinical presentations. They include disorders of the RAS-pathway, the PI3 Kinase pathway, JAK/ STAT pathways, the NFkB pathway and the CTLA4 checkpoint pathway. Amongst these genes recently associated with an ALPS-like phenotype is STAT3 (Signal transducer and activator of transcription 3) [2e4]. > Janus tyrosine kinases (JAKs) and STATs are crucial proteins in signal transduction initiated by a wide range of cytokines [5] and growth factors [6]. The important functions of the JAK-STAT signaling components in the control of the immune system homeostasis have been demonstrated by genetic knockout studies [7e9]. STAT3 is essential for vertebrate development [10] and plays a critical role in regulating key physiological functions in tissues, including the innate and adaptive immune responses [11].

[2] Pediatric lymphoproliferative disorders – Emerging insights and management: A narrative review

  • Authors: E. I. Obeagu
  • Year: 2026
  • Venue: Medicine
  • URL: https://www.semanticscholar.org/paper/c863790c34ecacab3322012ad2a9012ae860a9d2
  • DOI: 10.1097/MD.0000000000047367
  • PMID: 41578561
  • PMCID: 12851739
  • Summary: Challenges persist in ensuring equitable access to advanced diagnostics and therapies, particularly in resource-limited settings, and optimizing treatment regimens to minimize long-term complications and improve quality of life remains a critical area of focus.
  • Evidence snippets:
  • Snippet 1 (score: 0.455) > Pediatric lymphoproliferative disorders (PLPDs) encompass a spectrum of conditions marked by the abnormal proliferation of lymphocytes, often linked to genetic mutations, immune dysregulation, and infectious agents like Epstein–Barr virus. These disorders present with varied clinical phenotypes, ranging from benign lymphadenopathy to severe, life-threatening malignancies. Recent advancements in molecular diagnostics and imaging have significantly enhanced the early identification and classification of PLPDs, paving the way for timely and effective interventions. Understanding the pathophysiological mechanisms underlying PLPDs has also been instrumental in guiding the development of novel therapeutic strategies. The management of PLPDs has evolved with the advent of targeted therapies, including monoclonal antibodies and small molecule inhibitors, which have demonstrated promising efficacy in mitigating disease progression. For severe or refractory cases, hematopoietic stem cell transplantation remains a curative option, especially for disorders associated with primary immunodeficiencies. Despite these advancements, challenges persist in ensuring equitable access to advanced diagnostics and therapies, particularly in resource-limited settings. Furthermore, optimizing treatment regimens to minimize long-term complications and improve quality of life remains a critical area of focus.

[3] Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy

  • Authors: S. Mancuso, Marta Mattana, M. Carlisi, M. Santoro, S. Siragusa
  • Year: 2022
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/7c7575b1a80f5db2990660562a0d07f2b2f7d3e7
  • DOI: 10.3390/ijms23063368
  • PMID: 35328789
  • PMCID: 8952275
  • Citations: 19
  • Summary: The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.
  • Evidence snippets:
  • Snippet 1 (score: 0.439) > B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune system a critical target for new therapies. In the current therapeutic scenario enriched by chemo-free regimens, it is important to establish the effect of various drugs on the disease, as well as on the restoration of immune functions. In fact, treatment of B-cell lymphoma with passive immunotherapy that targets tumor cells or targets the tumor microenvironment, together with adoptive immunotherapy, is becoming more frequent. The aim of this review is to report relevant data on the evolution of the immune system during and after treatment with targeted therapy of B-cell lymphomas.

[4] Clinical and functional characterization of a novel TNFRSF9 variant causing immune dysregulation with predisposition to EBV-driven lymphomagenesis

  • Authors: P. Zhao, Kailan Chen, Li Yang, Chunhui Wan, Lei Zhang et al.
  • Year: 2025
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/21b103b886f3d12184b4d129751acdd4862dfb84
  • DOI: 10.3389/fimmu.2025.1605221
  • PMID: 40843003
  • PMCID: 12364884
  • Summary: The findings expand the mutation spectrum of the TNFRSF9 gene and provide new insights into the molecular mechanisms underlying this rare immunodeficiency disorder.
  • Evidence snippets:
  • Snippet 1 (score: 0.435) > EBV-specific immunity relies on robust cellular and humoral immune responses, with CD8+ cytotoxic T cells playing a critical role in controlling EBV infection. Patients with genetic variants affecting T-cell development and function are highly susceptible to chronic EBV infection (14). Growing evidence suggests that genetic defects impairing immune surveillance pathways increase susceptibility to EBV-associated lymphoproliferative disease (EBV + LPD) (4). To date, over 20 monogenic disorders, including variants in CD27, CD70, SH2D1A, ITK, MAGT1, PRKCD, PIK3CD, CORO1A, RASGRP1 and CTPS1, have linked to immune dysregulation and susceptibility to EBV-driven B cell lymphoproliferative disorders (15)(16)(17). These defects impair virusspecific T-cell responses, highlighting critical pathways required for immune control of EBV. Research on these patients has offered valuable insights into the mechanisms of immune surveillance against EBV and the pathogenesis of EBV-driven malignancies. > In this study, we report a case presenting with EBV viremia, recurrent respiratory infections, and Burkitt lymphoma. By nextgeneration sequencing, a novel homozygous missense variant (c.359G>C, p.C120S) in the TNFRSF9 gene was identified. Functional studies revealed that the p.C120S variant reduced TNFRSF9 expression at both mRNA and protein levels, impaired AKT and NF-kB signaling pathways. These findings underscore the critical role of TNFRSF9 in maintaining immune homeostasis and controlling EBV infection, and highlight the importance of molecular diagnostics in guiding targeted therapies for Inborn Errors of Immunity. > A review of the literature revealed only nine reported patients of TNFRSF9 deficiency, with significant clinical heterogeneity even among patients carrying the same variant (Table 2).

[5] Investigating the role of NPR1 in dilated cardiomyopathy and its potential as a therapeutic target for glucocorticoid therapy

  • Authors: Yaomeng Huang, Tongxin Li, Shichao Gao, Shuyu Li, Xiaoran Zhu et al.
  • Year: 2023
  • Venue: Frontiers in Pharmacology
  • URL: https://www.semanticscholar.org/paper/be229f6f2059faab4c97ec0a04bd055adab9dfe1
  • DOI: 10.3389/fphar.2023.1290253
  • PMID: 38026943
  • PMCID: 10662320
  • Citations: 3
  • Summary: Natriuretic peptide receptor 1 (NPR1) was identified as a core gene associated with DCM through bioinformatics analysis and led to substantial improvements in cardiac and renal function, accompanied by an upregulation of NPR1 expression.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > Multiple pathways and molecules are involved in this process; however, the detailed underlying mechanisms remain unclear. In recent years, with the development of high-throughput sequencing and gene chip technologies, the use of bioinformatics technology to explore the occurrence, development, and prognosis of diseases has become a hot topic for scholars worldwide (Hwang et al., 2018;Nayor et al., 2019;Rinschen et al., 2019;Sturm et al., 2019;Montaner et al., 2020). > The present study aimed to use bioinformatics technology to screen for DCM-related genes and investigate their mechanisms, with the purpose of revealing the pathogenesis of DCM and seeking treatment methods. The GSE3586 dataset, containing expression profiles related to DCM, was selected from the Gene Expression Omnibus (GEO) database. This study aimed to predict the core genes that may play crucial roles in disease progression at the molecular level through the enrichment of relevant molecular pathways associated with DCM. Furthermore, the phenotype of the core genes was validated to further support the results of the bioinformatics analysis through basic and clinical experiments. Additionally, the role of glucocorticoids in DCM treatment is discussed in this article with the purpose of providing a theoretical and experimental basis for exploring the pathogenesis of DCM and elucidating therapeutic methods. This study also provides a theoretical reference for the interpretation, early diagnosis, and treatment of DCM.

[6] Inborn Errors of Immunity With Immune Dysregulation: From Bench to Bedside

  • Authors: O. Delmonte, R. Castagnoli, Enrica Calzoni, L. Notarangelo
  • Year: 2019
  • Venue: Frontiers in Pediatrics
  • URL: https://www.semanticscholar.org/paper/3b1a3d33817709ddb2b6cb09f861f81b11721d57
  • DOI: 10.3389/fped.2019.00353
  • PMID: 31508401
  • PMCID: 6718615
  • Citations: 91
  • Influential citations: 2
  • Summary: The clinical and laboratory features of various recently described inborn errors of immunity associated with immune dysregulation and hyperinflammation in which mechanism-based therapeutic approaches have been implemented are summarized.
  • Evidence snippets:
  • Snippet 1 (score: 0.419) > With the increased availability of high-throughput DNA sequencing, the number of genes associated with inborn errors of immunity [historically named primary immune deficiency disorders (PIDs)] has exponentially increased over the last decade. The most recent PID classification from the International Union of Immunological Sciences includes more than 350 genes, and ∼50 of these have been discovered in the last 2 years (1). In addition to the identification of novel PID-associated genes, it has been recognized that distinct clinical phenotypes may be sustained by Gain of Function (GOF) or Loss of Function (LOF) mutations in the same gene. Finally, various degrees of activity of mutant proteins due to hypomorphic and hypermorphic mutations may also cause PID phenotypic variability (1,2). > The clinical features of PIDs are broad, ranging from increased susceptibility to infections to significant immune dysregulation, often leading to multiple autoimmune phenomena, including cytopenias and solid organ autoimmunity, in addition to lymphoproliferation and malignancy. The treatment of immune disorders with coexisting immune deficiency and immune dysregulation is challenging, as it requires careful balancing of immunosuppression in subjects at increased risk of infections. In most recent years, the growing ability to define PID pathophysiology at the molecular level has set the basis for the development of targeted therapeutic interventions. New drugs have been developed or repurposed to modulate intracellular pathways whose function is increased or diminished as a result of a specific genetic defect ( Table 1). Such a "precision medicine" approach often permits to selectively target a specific cell function instead of broadly affecting the entire immune system, and may even permit to avoid deleterious side effects on other tissues. In this manuscript, we summarize the laboratory and clinical features of various recently described PIDs, focusing in particular on disorders associated with immune dysregulation in which targeted therapeutic approaches have been implemented according to the recent knowledge of the molecular mechanisms underpinning these diseases and the most common clinical manifestations.

[7] Restoration of the immune function as a complementary strategy to treat Chronic Lymphocytic Leukemia effectively

  • Authors: C. Moreno, C. Muñoz, M. Terol, J. Hernández‐Rivas, Miguel Villanueva
  • Year: 2021
  • Venue: Journal of Experimental & Clinical Cancer Research : CR
  • URL: https://www.semanticscholar.org/paper/138daa4ae761d5f2195d43842b98843f2f427564
  • DOI: 10.1186/s13046-021-02115-1
  • PMID: 34654437
  • PMCID: 8517318
  • Citations: 31
  • Summary: It is proposed that a dual therapeutic approach, acting directly against malignant B-cells and restoring the immune function is clinically relevant and should be considered when developing future strategies to treat patients with CLL.
  • Evidence snippets:
  • Snippet 1 (score: 0.415) > Chronic Lymphocytic Leukemia (CLL) is the most common B-cell malignancy in the Western world [1]. CLL is a lymphoproliferative disease characterized by the accumulation of mature monoclonal B-cells with a typical immunophenotype (i.e, CD5+CD23+ and other B-cell markers) which accumulate in peripheral blood, bone marrow and lymph nodes. A hallmark of the pathophysiology of CLL is the dysfunction of the immune system which is mostly translated in a state of humoral and cellular immunodeficiency and higher prevalence of autoimmune disorders [2,3]. > In CLL, tumor cells influence the immune system to escape immunosurveillance and create an immunosuppressive microenvironment. In general, there are four mechanisms used by CLL cells to escape from the control of immune cells: (1) non-immunogenic tumor cell death; (2) expansion and recruitment of immunosuppressive cells, including T regulatory (T-reg) cells, M2 macrophages and myeloid-derived suppressor cells (MDSC); > (3) depletion and/or inhibition of antitumor immune cells such as Th1 T-cells and CD8+ cells; and (4) production of immunosuppressive soluble factors such as IL-10 and TGF-β [4]. These changes are highly relevant for the maintenance and progression of the tumor and contribute to the complex manifestations of the disease. Recently, it has been reported that immune microenvironment plays a significant role in progression of the disease in contrast to clonal evolution [5]. > At the end of the 90´s, the introduction of chemotherapy in combination with anti-CD20 monoclonal antibodies such as rituximab was an important step forward in CLL therapy and the outcome of patients significantly improved. However, most patients will eventually relapse. Importantly, CIT decreases the disease burden but, at the same time, exacerbates certain defects of an already dysfunctional immune system which further impacts patients' health, with increased infection morbidity and secondary neoplasms [6].

[8] Immune Dysregulation in Autism Spectrum Disorder: What Do We Know about It?

  • Authors: M. Robinson-Agramonte, Elena Noris García, Jarasca Fraga Guerra, Yamilé Vega Hurtado, Nicola Antonucci et al.
  • Year: 2022
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/0d5e761dc4d912894a808ce3353286fc759f2ee5
  • DOI: 10.3390/ijms23063033
  • PMID: 35328471
  • PMCID: 8955336
  • Citations: 132
  • Influential citations: 1
  • Summary: Current insights into immune dysfunction in ASD are summarized, with particular reference to the impact of immunological factors related to the maternal influence of autism development; comorbidities influencing autism disease course and severity; and others factors with particular relevance, including obesity.
  • Evidence snippets:
  • Snippet 1 (score: 0.413) > Neuropsychiatric and neurodegenerative disorders display a biologically defined expression related to brain dysfunctions and age-related disease onset. The former, considered as a disturbed behavior and emotional state derived from the functional brain impairment, and the latter, viewed as an organic brain disease where the symptoms follow the damage of specific brain regions. Studies from different groups show biological evidence for the presence of common immune-mediated mechanisms overlapping both disease processes, although understandably with some distinctive characteristics. > Clinical and experimental evidence have argued similar mechanisms of innate immunity pathway signaling overlapping immune-pathological events in both neuropsychiatric and neurodegenerative disorders, characterized by the common influence of resident glial cells mediating inflammation via soluble molecules (mainly cytokines, chemokines, and complement proteins), which promote the recruitment of local immune cells and others coming from the peripheral compartment. To show this evidence, we refer to two pathologies occurring in the both extremes of the life: ASD, the main object of this review, and Parkinson disease (PD), following the main aspects of innate immunity relevant to both disorders and where the glial cells are the main cellular element. > In general, both disorders, ASD and PD, are related to brain dysfunctions, and in their particular context, genetic causes and risk factors play a central role in disease pathophysiology, severity, and disease progression besides the overlapping immunopathological mechanisms and molecular pathways. More than 100 candidate genes identified in ASD may converge as causal factors related to neuronal development, plasticity, synaptic structure, and performance [230,231]. Several genes and genomic regions, including alpha-synuclein (SNCA), parkinRBRE3 ubiquitin protein ligase (PARK2), chromosome 22q11deletion/DiGeorge region, and fragile X mental retardation 1 (FMR1) repeats, may be relevant to the development of both ASD and PD, with converging features related to synaptic function and neurogenesis. Both PD and ASD also show alterations and impairments at the synaptic level, representing early main disease phenotypes converging upon mechanisms active in the two diseases [232].

[9] X-linked lymphoproliferative disease type 1: a clinical and genetic update

  • Authors: Jiaxun Li, Luyu Lv, Qingqing Wei, Wenpeng Pang, Chunjuan He et al.
  • Year: 2025
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/1b22fc5c7707c76b775f2b5d18b5697b64432ff0
  • DOI: 10.3389/fimmu.2025.1620327
  • PMID: 40574867
  • PMCID: 12198186
  • Citations: 1
  • Summary: Establishing a definitive correlation between specific genotypes and clinical phenotypes remains challenging, but emerging evidence suggests a potential association, and underscores the critical need for further large-scale studies to elucidate this relationship.
  • Evidence snippets:
  • Snippet 1 (score: 0.411) > X-linked lymphoproliferative disease (XLP), also known as Duncan’s disease, is a primary immunodeficiency disorder linked to the X chromosome. In 1998, SH2D1A, which encodes the signaling lymphocyte activation molecule (SLAM)-associated protein (SAP), was identified as the first pathogenic gene associated with XLP. To date, more than 100 mutation sites in this gene have been documented. The disease is associated with infection with Epstein-Barr virus (EBV) and characterized by hemophagocytic lymphohistiocytosis (HLH), hypogammaglobulinemia, and lymphomas. Pathogenesis is intricately associated with cell type-specific SAP-SLAM signaling pathways. Particularly, the immune cell defects involve impaired T cell-B cell interactions, reduced cytotoxicity of Natural Killer (NK) cells, and abnormal development of Natural Killer T (NKT) cells. These factors collectively increase susceptibility to EBV and drive clinical manifestations in XLP type 1 (XLP1) patients. Although establishing a definitive correlation between specific genotypes and clinical phenotypes remains challenging, emerging evidence suggests a potential association. This underscores the critical need for further large-scale studies to elucidate this relationship. Given the current understanding of the pathophysiological mechanisms associated with XLP1, specific treatments to normalize SAP expression and restore immune tolerance in XLP1 patients play an important role. In addition to the necessity for long-term studies to verify the efficacy and safety of hematopoietic stem cell transplantation (HSCT), gene therapies currently under development, along with other emerging treatments, exhibit substantial promise for future clinical applications.

[10] Primer immunhiány és autoimmun betegségek

  • Authors: G. Műzes, Ferenc Sipos
  • Year: 2018
  • Venue: Orvosi Hetilap
  • URL: https://www.semanticscholar.org/paper/b4e357ef596804bffea77a9812d9704dbf2e4026
  • DOI: 10.1556/650.2018.31064
  • Summary: The case presented finally highlights that both the recognition of autoimmune diseases in association with Immunodeficiencies and the diagnosis of immunodefiency in those phenotypes with predominant autoimmunity could be challenging.
  • Evidence snippets:
  • Snippet 1 (score: 0.411) > Abstract: Primary immunodeficiencies consist of a group of genetically heterogeneous immune disorders affecting distinct elements of the innate and adaptive immune system. Patients with primary immunodeficiency are more prone to develop not only recurrent infections, but non-infectious complications, like inflammatory or granulomatous conditions, lymphoproliferative and solid malignancies, autoinflammatory disorders, and a broad spectrum of autoimmune diseases. The concomitant appearance of primary immunodeficiency and autoimmunity appears to be rather paradoxical, therefore making the diagnosis of immunodeficiency patients with autoimmune complications challenging. Mutations of one or more genes playing a fundamental role in immunoregulation and/or immune tolerance network are thought to be responsible for primary immunodeficiencies. The diverse immunological abnomalities along with the compensatory and excessive sustained inflammatory response result in tissue damage and finally in manifestation of organ-, cell-specific or systemic autoimmune diseases. Several forms of primary immunodeficiency disorders are characterized by a variety of specific autoimmune phenomena. This overview addresses the spectrum of autoimmune diseases associated with primary immunodeficiencies, and explores the molecular and cellular mechanisms underlying abnormalities of the immune system. The case presented finally highlights that both the recognition of autoimmune diseases in association with immunodeficiencies and the diagnosis of immunodefiency in those phenotypes with predominant autoimmunity could be challenging. Orv Hetil. 2018; 159(23): 908–918.

[11] Organoids in gastrointestinal diseases: from bench to clinic

  • Authors: Qinying Wang, Fanying Guo, Qinyuan Zhang, Tingting Hu, Yutao Jin et al.
  • Year: 2024
  • Venue: MedComm
  • URL: https://www.semanticscholar.org/paper/9b8880d8b9d45670da950197d7e353794f51d09e
  • DOI: 10.1002/mco2.574
  • PMID: 38948115
  • PMCID: 11214594
  • Citations: 12
  • Summary: A comprehensive and systematical depiction of organoids models is drawn, providing a novel insight into the utilization of organoids models from bench to clinic and clinical adhibition.
  • Evidence snippets:
  • Snippet 1 (score: 0.410) > Organoids models offer a robust platform for investigating the potential mechanisms of GI diseases and evaluating potential therapeutic interventions.By culturing organoids derived from patients' tissues or stem cells, researchers can delve into disease-specific cellular and molecular pathways, encompassing aberrant cell signaling, perturbed immune responses, and dysfunctional metabolic processes.These disease-specific phenotypes enable the study of disease progression, screening of prospective therapeutics, as well as identification of novel drug targets and mechanisms of action for GI diseases in a clinically relevant context.

[12] [Primary immunodeficiency and autoimmune diseases].

  • Authors: G. Műzes, F. Sipos
  • Year: 2018
  • Venue: Orvosi hetilap
  • URL: https://www.semanticscholar.org/paper/14a8db6d56e353b48c82e510366b6fe608ff76bb
  • DOI: 10.1556/650.2018.31064
  • PMID: 29860882
  • Citations: 5
  • Summary: The case presented finally highlights that both the recognition of autoimmune diseases in association with Immunodeficiencies and the diagnosis of immunodefiency in those phenotypes with predominant autoimmunity could be challenging.
  • Evidence snippets:
  • Snippet 1 (score: 0.409) > Primary immunodeficiencies consist of a group of genetically heterogeneous immune disorders affecting distinct elements of the innate and adaptive immune system. Patients with primary immunodeficiency are more prone to develop not only recurrent infections, but non-infectious complications, like inflammatory or granulomatous conditions, lymphoproliferative and solid malignancies, autoinflammatory disorders, and a broad spectrum of autoimmune diseases. The concomitant appearance of primary immunodeficiency and autoimmunity appears to be rather paradoxical, therefore making the diagnosis of immunodeficiency patients with autoimmune complications challenging. Mutations of one or more genes playing a fundamental role in immunoregulation and/or immune tolerance network are thought to be responsible for primary immunodeficiencies. The diverse immunological abnomalities along with the compensatory and excessive sustained inflammatory response result in tissue damage and finally in manifestation of organ-, cell-specific or systemic autoimmune diseases. Several forms of primary immunodeficiency disorders are characterized by a variety of specific autoimmune phenomena. This overview addresses the spectrum of autoimmune diseases associated with primary immunodeficiencies, and explores the molecular and cellular mechanisms underlying abnormalities of the immune system. The case presented finally highlights that both the recognition of autoimmune diseases in association with immunodeficiencies and the diagnosis of immunodefiency in those phenotypes with predominant autoimmunity could be challenging. Orv Hetil. 2018; 159(23): 908-918.

[13] Hyper-IgE Syndrome: A Case Report with Insights from Bioinformatics Analysis of Key Pathways and Genes

  • Authors: Juan Li, Wei Han, Meng-Yu Zhang, Jia-Qi Fan, Guo-Dong Li et al.
  • Year: 2025
  • Venue: Infection and Drug Resistance
  • URL: https://www.semanticscholar.org/paper/c9acdd456b694d70efd877736518d7d6c2f818f6
  • DOI: 10.2147/IDR.S507797
  • PMID: 40162035
  • PMCID: 11952148
  • Summary: This study identified IL6, CDH2, and CLDN1 as key factors in HIES progression, suggesting naive B cells and dormant mast cells may be involved, suggesting naive B cells and dormant mast cells may be involved.
  • Evidence snippets:
  • Snippet 1 (score: 0.408) > Researchers have utilized gene sequencing techniques to identify multiple mutation sites associated with HIES, further exploring the dysregulation of immune system signaling pathways. 4,11,12 Current diagnostic and therapeutic approaches primarily rely on clinical evaluation and symptom management, which often fail to address the underlying genetic and molecular mechanisms of the disease. 13 Although advancements in genetic sequencing have provided some insights, the complexity of HIES pathophysiology remains inadequately understood. Bioinformatics offers a powerful approach to uncovering the genetic and molecular mechanisms of rare diseases like HIES, which may not be evident through clinical observation alone. 1 By integrating genomic, transcriptomic, and proteomic data, novel genetic variants and molecular pathways associated with HIES can be identified. 1,14 Whole-exome sequencing (WES) is employed to detect mutations in key immune-related genes, while RNA sequencing (RNA-seq) analysis provides insights into differential gene expression patterns, highlighting dysregulated immune signaling pathways and offering a comprehensive view of the molecular landscape of HIES. 9 Although HIES is a rare disorder, as our understanding of it deepens, we look forward to providing more effective treatment options and strategies to improve the quality of life for patients. Future research will continue to unveil the pathogenesis of HIES and explore novel therapeutic approaches to help patients better manage and cope with this condition. By advancing our knowledge in this field, we aim to enhance the overall care and outcomes for individuals affected by HIES. In this report, we presented a case diagnosed with HIES and conducted bioinformatics and immune infiltration analyses to reveal underlying genetic variants and molecular pathways that were difficult to detect through traditional clinical observation. By leveraging bioinformatics tools, this study aimed to elucidate the complex mechanisms behind HIES, ultimately contributing to the identification of new therapeutic targets and enhancing the overall understanding of this rare disease.

[14] Editorial: Human Disorders of PI3K Biology

  • Authors: C. Lucas, S. Tangye
  • Year: 2020
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/1bed33976a1ac681effe494bb0dc6e5633b70c3b
  • DOI: 10.3389/fimmu.2020.617464
  • PMID: 33329612
  • PMCID: 7732539
  • Citations: 2
  • Summary: This Research Topic, 13 manuscripts cover a range of subjects, mostly centered around findings in APDS and cancer, and structural biology concepts for Class IA PI3K variants in cancer and immunodeficiency are reviewed.
  • Evidence snippets:
  • Snippet 1 (score: 0.406) > presentation for these conditions usually begins with recurrent respiratory infections very early in life, followed by lymphoproliferative disorders, and then with gastrointestinal conditions and autoimmune cytopenias. Inhibition of mechanistic target of rapamycin (mTOR), a regulator of cell proliferation and growth downstream of PI3Kd, with rapamycin (sirolimus) is effective at mitigating lymphoproliferative disease in APDS but has had limited effect on managing other features of disease. Coulter and Cant discuss in more depth potential therapeutic approaches. APDS patients have various clinical manifestations with some patients being asymptomatic while others exhibiting recurrent infections and antibody defects. Historically, conventional therapies such as immunoglobulin replacement therapy, HSCT, and antimicrobial prophylaxis have been used as treatments. However, the heterogeneity of disease presentation requires a more tailored approach which can be achieved through the use of selective PI3Kd inhibitors such as Leniolisib. > Wentink et al. provide new data on the phenotype of CD8 + T cells in APDS as it relates to exhaustion. As a contributing mechanism for increased susceptibility to infections and dysregulated immune responses, CD8 + T cell exhaustion due to chronic T cell stimulation and proliferation is relevant for APDS pathology. Cannons et al. provide a perspective piece on the survival, differentiation, and function of CD8 + T cells in APDS. Despite having a normal or even elevated frequency of Epstein-Barr Virus (EBV)-specific CD8 + T cells, APDS patients have defects in controlling EBV and cytomegalovirus viremia. While seemingly not affecting the development of antigenspecific T cells, hyperactive PI3Kd impacts CD8 + T cell proliferation, differentiation, and survival, which have direct relevance for their function in vivo. Cohen covers consequences of herpesvirus infections in APDS in more depth. Herpesviruses can directly bind surface receptors that activate the PI3Kd pathway and further modulate signaling through viral proteins.

[15] T Cell Repertoire Analysis as a Molecular Signature of the Spectrum of T-LGL Lymphoproliferative Disorders: Tracing the Literature

  • Authors: E. Stalika, Ioannis Tsamesidis
  • Year: 2025
  • Venue: Current Issues in Molecular Biology
  • URL: https://www.semanticscholar.org/paper/ed70f16f28da3ed8937af55e88d5ef33b22cdd0e
  • DOI: 10.3390/cimb47040264
  • PMID: 40699662
  • PMCID: 12025433
  • Summary: In the ontogeny and evolution of T-LGL leukemia, repertoire limits, public clonotypes, and clonal drift all clearly show selection by limited antigens, and the progression from a polyclonal cytotoxic response to the emergence of T-LGL leukemia is slow.
  • Evidence snippets:
  • Snippet 1 (score: 0.404) > Cytotoxic T lymphocyte lymphoproliferative disorders may be chronic or transient and occur in the context of heterogeneous clinical entities, e.g., coexisting with viral infections, autoimmune disorders or developing after organ or allogeneic hematopoietic cell transplantation [6][7][8]10,12,15,16,[59][60][61][62]. Disorders in the mechanism of T lymphocyte apoptosis are believed to lead to the development of T lymphoproliferative diseases [34,[63][64][65]; however, the ontogeny of these diseases has not been fully elucidated. It is believed that chronic persistent antigenic stimulation or some perturbation in the mechanism of T-cytotoxic lymphocyte apoptosis maintains the persistence of clonal outgrowths and eventual disease manifestation [28,66,67]. The nature of the antigens involved remains to be determined. > In the above context, the analysis of T cell receptor gene rearrangements in these entities may provide clues of the role of antigen in pathogenesis and possibly disease progression, assuming that intense antigenic stimulation initially leads to polyclonal hyperplasia and, under as yet unknown conditions (which could include genetic predisposition), may result in clonal disease, e.g., T-LGL leukemia [68]. > In the last decade, the advent of high-throughput sequencing methodology and its application to T cell receptor repertoire studies in a wide range of physiological and pathological conditions has revolutionized immunogenetics [10,[69][70][71][72][73][74][75][76]. A major challenge for the scientific community is the standardization of the experimental procedure and the development of bioinformatics approaches specifically designed for the analysis of immunogenetic data derived from high-throughput sequencing methods.

[16] Integration of Immunome With Disease-Gene Network Reveals Common Cellular Mechanisms Between IMIDs and Drug Repurposing Strategies

  • Authors: Abhinandan Devaprasad, T. Radstake, A. Pandit
  • Year: 2019
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/da3d168a672593e5da82bb4178e49118bc4b3170
  • DOI: 10.3389/fimmu.2021.669400
  • PMID: 34108969
  • PMCID: 8181425
  • Citations: 13
  • Summary: The method identified top DACs, DAGs, common pathways, and proposed potential drug repurposing targets between IMIDs and built the DIME tool, paving way for future (pre-)clinical research.
  • Evidence snippets:
  • Snippet 1 (score: 0.404) > Objective Development and progression of immune-mediated inflammatory diseases (IMIDs) involve intricate dysregulation of the disease associated genes (DAGs) and their expressing immune cells. Due to the complex molecular mechanism, identifying the top disease associated cells (DACs) in IMIDs has been challenging. Here, we aim to identify the top DACs and DAGs to help understand the cellular mechanism involved in IMIDs and further explore therapeutic strategies. Method Using transcriptome profiles of 40 different immune cells, unsupervised machine learning, and disease-gene networks, we constructed the Disease-gene IMmune cell Expression (DIME) network, and identified top DACs and DAGs of 12 phenotypically different IMIDs. We compared the DIME networks of IMIDs to identify common pathways between them. We used the common pathways and publicly available drug-gene network to identify promising drug repurposing targets. Result We found CD4+Treg, CD4+Th1, and NK cells as top DACs in the inflammatory arthritis such as ankylosing spondylitis (AS), psoriatic arthritis, and rheumatoid arthritis (RA); neutrophils, granulocytes and BDCA1+CD14+ cells in systemic lupus erythematosus and systemic scleroderma; ILC2, CD4+Th1, CD4+Treg, and NK cells in the inflammatory bowel diseases (IBDs). We identified lymphoid cells (CD4+Th1, CD4+Treg, and NK) and their associated pathways to be important in HLA-B27 type diseases (psoriasis, AS, and IBDs) and in primary-joint-inflammation-based inflammatory arthritis (AS and RA). Based on the common cellular mechanisms, we identified lifitegrast as potential drug repurposing candidate for Crohn’s disease, and other IMIDs. Conclusion Our method identified top DACs, DAGs, common pathways, and proposed potential drug repurposing targets between IMIDs. To extend our method to other diseases, we built the DIME tool. Thus paving way for future (pre-)clinical research.

[17] Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight

  • Authors: F. Iheagwam, A. J. Joseph, E. D. Adedoyin, Olawumi Toyin Iheagwam, Samuel Akpoyowvare Ejoh
  • Year: 2025
  • Venue: Pathophysiology
  • URL: https://www.semanticscholar.org/paper/dbf8042761c1a5fc50f8cd894cc498505abac7cb
  • DOI: 10.3390/pathophysiology32010009
  • PMID: 39982365
  • PMCID: 12077258
  • Citations: 26
  • Summary: This review aims to elucidate the complex link between mitochondrial dysfunction and diabetes, covering the spectrum of diabetes types, the role of mitochondria in insulin resistance, highlighting pathophysiological mechanisms, mitochondrial DNA damage, and altered mitochondrial biogenesis and dynamics.
  • Evidence snippets:
  • Snippet 1 (score: 0.403) > The landscape of DM research is continuously evolving, with emerging technologies and approaches offering new insights into the pathophysiology of the disease and potential therapeutic targets. Advancements in omics technologies, encompassing genomes, transcriptomics, proteomics, and metabolomics, have transformed the molecular mechanisms underlying DM [134]. High-throughput sequencing techniques enable comprehensive analysis of genetic variants, gene expression profiles, protein abundance, and metabolite levels associated with DM and its complications [135]. Single-cell omics approaches provide unprecedented resolution and granularity, allowing researchers to dissect cellular heterogeneity and identify novel cell types, subpopulations, and signalling pathways involved in DM pathogenesis. Integrating multi-omics data sets offers a systems-level perspective of DM, unravelling complex networks of molecular interactions and regulatory circuits underlying disease progression [136]. > In addition to omics technologies, advances in imaging modalities, such as MRI, PET, and optical imaging, enable non-invasive visualisation and quantification of metabolic, functional, and structural changes. Molecular imaging probes targeting specific biomarkers and metabolic pathways provide valuable insights into disease mechanisms and treatment responses in preclinical and clinical settings [85]. Despite significant progress in DM research, numerous unanswered questions and knowledge gaps persist, hindering the ability to develop effective prevention and treatment strategies. Key areas requiring further investigation include the role of epigenetics, environmental factors, and the microbiome in DM susceptibility and progression. Moreover, the interaction between environmental cues and genetic predisposition remains incompletely understood, highlighting the need for comprehensive multi-omics studies and large-scale epidemiological analyses to identify gene-environment interactions and modifiable risk factors for DM [137]. Furthermore, the heterogeneity of DM phenotypes and clinical outcomes poses a challenge for personalised medicine approaches, necessitating robust biomarkers and predictive models to stratify patients based on disease subtypes, prognosis, and treatment response [138].

[18] Exploring the molecular mechanisms of subarachnoid hemorrhage and potential therapeutic targets: insights from bioinformatics and drug prediction

  • Authors: Yi Liu, Yang Zhang, Huan Wei, Li Wang, Lishang Liao
  • Year: 2025
  • Venue: Scientific Reports
  • URL: https://www.semanticscholar.org/paper/19a91d9c8cabec6a5a186729d545077e252ecb67
  • DOI: 10.1038/s41598-025-97642-8
  • PMID: 40229542
  • PMCID: 11997208
  • Summary: The findings not only elucidate the molecular mechanisms underlying SAH but also provide robust bioinformatics and experimental evidence supporting IRN as a promising therapeutic candidate, offering novel insights for future intervention strategies in SAH.
  • Evidence snippets:
  • Snippet 1 (score: 0.403) > involved in SAH pathology. As a result, our understanding of the cellular composition and microenvironment in SAH remains incomplete 8 . > Advances in bioinformatics provide powerful tools to analyze large-scale gene expression data and understand complex biological processes. By integrating transcriptomic data with immune cell infiltration analysis, we can gain a deeper understanding of the molecular mechanisms underlying SAH and identify potential key genes as therapeutic targets 9,10 . Previous studies have indicated that inflammation, oxidative stress, and cell death play crucial roles in the development of SAH, processes that are often closely associated with changes in specific cell types and immune responses 11 . > The goal of this study is to explore the molecular mechanisms of SAH, with a focus on immune cell infiltration and its role in disease progression. We aim to identify key genes and signaling pathways associated with SAH and investigate potential therapeutic strategies. Specifically, we will examine Isorhynchophylline (IRN) as a potential treatment for SAH and analyze its effects on relevant targets and signaling pathways. Through a comprehensive understanding of the pathological features of SAH, this study aims to provide valuable insights into future clinical interventions and treatment strategies.

[19] New therapeutic targets in rare genetic skeletal diseases

  • Authors: M. Briggs, Peter A. Bell, M. Wright, K. A. Pirog
  • Year: 2015
  • Venue: Expert Opinion on Orphan Drugs
  • URL: https://www.semanticscholar.org/paper/1363107f71ae6d2d60abca471cddf3da5d13644b
  • DOI: 10.1517/21678707.2015.1083853
  • PMID: 26635999
  • PMCID: 4643203
  • Citations: 37
  • Influential citations: 1
  • Summary: An overview of disease mechanisms that are shared amongst groups of different GSDs and potential therapeutic approaches that are under investigation are described to generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.
  • Evidence snippets:
  • Snippet 1 (score: 0.403) > proteins of the cartilage ECM such as type II collagen [50]. However, emerging knowledge suggests that the primary genetic defect may be less important than the cells' response to the expression of the mutant gene product [107]. Moreover, the largely overlooked response of a cell (i.e. chondrocyte) to the abnormal extracellular environment is also important for disease progression as illustrated by several GSDs discussed in this review. > It is important that 'omics'-based approaches and technologies are systematically applied to the study of rare GSDs so that definitive reference profiles and disease signatures are generated for each phenotype. These can then be used in a Systems Biology approach to identify both common and dissimilar pathological signatures and disease mechanisms. This approach is entirely dependent upon relevant in vitro and in vivo models (and also novel 'disease-mechanism phenocopies' [107]) for testing new diagnostic and prognostic tools and for determining the molecular mechanisms that underpin the pathophysiology so that effective therapeutic treatments can be developed and validated. This approach will eventually lead to personalized treatments and care strategies centred on shared disease mechanisms with the use of relevant biomarkers to monitor the efficacy of treatment and disease progression. > It is vital that all relevant stakeholders are involved from the outset in defining the appropriate outcomes of any potential therapeutic regime. The perceptions of a successful therapy can differ widely between the clinical academic community and the relevant patient-support groups and it is vital that there is engagement on all these issues. > In summary, the identification of causative genes and mutations for GSDs over the last 20 years, coupled with the generation and in-depth analysis of a plethora of relevant cell and mouse models, has derived new knowledge on disease mechanisms and suggested potential therapeutic targets. The fast-evolving hypothesis that clinically disparate diseases can share common disease mechanisms is a powerful concept that will generate critical mass for the identification and validation of novel therapeutic targets and biomarkers.

[20] Navigating Drug-Induced Lung Disease (DILD): A Comprehensive Review on Management and Prevention Strategies

  • Authors: Srinivasulareddy Annareddy, B. Ghewade, Ulhas S Jadhav, Pankaj B Wagh
  • Year: 2024
  • Venue: Cureus
  • URL: https://www.semanticscholar.org/paper/0b389cda78d09ed43d6169972b6b2948590d3a59
  • DOI: 10.7759/cureus.69954
  • PMID: 39445304
  • PMCID: 11496594
  • Citations: 1
  • Influential citations: 1
  • Summary: This review provides a comprehensive overview of DILD, focusing on its definition, pathophysiology, and clinical implications, and examines future research directions and emerging therapies, aiming to enhance the understanding and management of DILD.
  • Evidence snippets:
  • Snippet 1 (score: 0.402) > The pathophysiology of drug-induced lung injury (DILI) is complex, involving various mechanisms that can lead to pulmonary complications. These mechanisms can be broadly categorized into two main types: direct toxicity and immune-mediated toxicity [1]. Direct toxicity occurs when a drug or its metabolites cause cellular damage without involving the immune system. This can happen through several pathways, such as producing reactive metabolites, oxidative stress, and direct cellular injury. For example, drugs like bleomycin can generate reactive oxygen species (ROS), leading to oxidative stress, cell injury, and apoptosis. Additionally, certain drugs can directly damage alveolar epithelial cells or endothelial cells, causing inflammation and pulmonary edema [13]. Immune-mediated lung injury involves an abnormal immune response triggered by drug exposure. This can manifest through allergic reactions, where drugs act as haptens and bind to proteins, eliciting an immune response. This can result in drug-induced pneumonitis, characterized by the infiltration of immune cells and cytokine release. Some medications can also induce systemic cytokine release, causing lung inflammation and damage, such as capillary leakage and pulmonary edema [14]. Genetic factors significantly influence susceptibility to drug-induced lung injury. Variability in drug metabolism and immune response can lead to idiosyncratic reactions, which are unpredictable and not dose-dependent. Genetic polymorphisms in genes encoding drug-metabolizing enzymes can affect the production of toxic metabolites, while preexisting lung conditions or genetic predispositions may increase the risk of developing DILI. Differences in immune system function among individuals can also result in varying responses to drugs, with some patients experiencing severe immune-mediated lung injury while others do not [15]. Understanding the pathophysiology of drug-induced lung injury, including the influence of genetic predisposition and idiosyncratic reactions, is crucial for identifying at-risk patients and developing effective prevention and management strategies. Ongoing research is essential to elucidate these mechanisms further and improve clinical outcomes for patients affected by drug-induced lung injury [16].

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.