A

Disease A

Slug:Autoimmune_Gastritis
B

Disease B

Slug:Hashimotos_Thyroiditis
G

Causal Mechanism Graphs

Autoimmune Gastritis

graph LR
    Achlorhydria["Achlorhydria"]
    CD4+_T_Cell_Mediated_Autoimmune_Response_Against_the_Gastric_Proton_Pump["CD4+ T Cell-Mediated Autoimmune Response Against the Gastric Proton Pump"]
    Peripheral_Neuropathy["Peripheral Neuropathy"]
    Somatostatin_Analog_Therapy["Somatostatin Analog Therapy"]
    Parietal_Cell_Destruction_and_Oxyntic_Atrophy["Parietal Cell Destruction and Oxyntic Atrophy"]
    Intrinsic_Factor_Deficiency_and_B12_Malabsorption["Intrinsic Factor Deficiency and B12 Malabsorption"]
    Hypergastrinemia_and_ECL_Cell_Hyperplasia["Hypergastrinemia and ECL Cell Hyperplasia"]
    Hypergastrinemia["Hypergastrinemia"]
    Netazepide_Gastrin_CCK2_Receptor_Antagonist["Netazepide (Gastrin/CCK2 Receptor Antagonist)"]
    Glossitis["Glossitis"]
    Atrophic_Gastritis["Atrophic Gastritis"]
    Endoscopic_Resection_of_Gastric_Neuroendocrine_Tumors["Endoscopic Resection of Gastric Neuroendocrine Tumors"]
    Iron_Deficiency_Anemia["Iron Deficiency Anemia"]
    Gastric_Adenocarcinoma["Gastric Adenocarcinoma"]
    Pernicious_Anemia["Pernicious Anemia"]
    Gastric_Neuroendocrine_Tumor["Gastric Neuroendocrine Tumor"]

    CD4+_T_Cell_Mediated_Autoimmune_Response_Against_the_Gastric_Proton_Pump --> Parietal_Cell_Destruction_and_Oxyntic_Atrophy
    Parietal_Cell_Destruction_and_Oxyntic_Atrophy --> Atrophic_Gastritis
    Parietal_Cell_Destruction_and_Oxyntic_Atrophy --> Achlorhydria
    Parietal_Cell_Destruction_and_Oxyntic_Atrophy --> Iron_Deficiency_Anemia
    Parietal_Cell_Destruction_and_Oxyntic_Atrophy --> Intrinsic_Factor_Deficiency_and_B12_Malabsorption
    Parietal_Cell_Destruction_and_Oxyntic_Atrophy --> Hypergastrinemia_and_ECL_Cell_Hyperplasia
    Parietal_Cell_Destruction_and_Oxyntic_Atrophy --> Gastric_Adenocarcinoma
    Intrinsic_Factor_Deficiency_and_B12_Malabsorption --> Pernicious_Anemia
    Intrinsic_Factor_Deficiency_and_B12_Malabsorption --> Peripheral_Neuropathy
    Intrinsic_Factor_Deficiency_and_B12_Malabsorption --> Glossitis
    Hypergastrinemia_and_ECL_Cell_Hyperplasia --> Hypergastrinemia
    Hypergastrinemia_and_ECL_Cell_Hyperplasia --> Gastric_Neuroendocrine_Tumor
    Netazepide_Gastrin_CCK2_Receptor_Antagonist --> Gastric_Neuroendocrine_Tumor
    Endoscopic_Resection_of_Gastric_Neuroendocrine_Tumors --> Gastric_Neuroendocrine_Tumor
    Somatostatin_Analog_Therapy --> Gastric_Neuroendocrine_Tumor

    style Achlorhydria fill:#fef3c7
    style CD4+_T_Cell_Mediated_Autoimmune_Response_Against_the_Gastric_Proton_Pump fill:#dbeafe
    style Peripheral_Neuropathy fill:#fef3c7
    style Somatostatin_Analog_Therapy fill:#fce7f3
    style Parietal_Cell_Destruction_and_Oxyntic_Atrophy fill:#dbeafe
    style Intrinsic_Factor_Deficiency_and_B12_Malabsorption fill:#dbeafe
    style Hypergastrinemia_and_ECL_Cell_Hyperplasia fill:#dbeafe
    style Hypergastrinemia fill:#fef3c7
    style Netazepide_Gastrin_CCK2_Receptor_Antagonist fill:#fce7f3
    style Glossitis fill:#fef3c7
    style Atrophic_Gastritis fill:#fef3c7
    style Endoscopic_Resection_of_Gastric_Neuroendocrine_Tumors fill:#fce7f3
    style Iron_Deficiency_Anemia fill:#fef3c7
    style Gastric_Adenocarcinoma fill:#fef3c7
    style Pernicious_Anemia fill:#fef3c7
    style Gastric_Neuroendocrine_Tumor fill:#fef3c7

Hashimotos Thyroiditis

graph LR
    Selenium_Deficiency["Selenium Deficiency"]
    CTLA4["CTLA4"]
    Iodine_Excess["Iodine Excess"]
    Free_T4["Free T4"]
    Autoimmune_Thyroid_Destruction["Autoimmune Thyroid Destruction"]
    Thyroglobulin_Hyperiodination_and_Neoantigen_Formation["Thyroglobulin Hyperiodination and Neoantigen Formation"]
    LAG3["LAG3"]
    Hepatitis_C_Virus_Infection["Hepatitis C Virus Infection"]
    Depression["Depression"]
    Vitamin_D_Deficiency["Vitamin D Deficiency"]
    Loss_of_Immune_Tolerance_to_Thyroid_Antigens["Loss of Immune Tolerance to Thyroid Antigens"]
    Dry_Skin["Dry Skin"]
    Impaired_Vitamin_D_Dependent_Immune_Tolerance["Impaired Vitamin D-Dependent Immune Tolerance"]
    Low_Vitamin_D_Intake_and_Cutaneous_Synthesis["Low Vitamin D Intake and Cutaneous Synthesis"]
    Thyroid_Hormone_Deficiency["Thyroid Hormone Deficiency"]
    Constipation["Constipation"]
    Vitamin_D_Supplementation["Vitamin D Supplementation"]
    NF_κB_IL_6_Signaling_Pathway_Activation["NF-κB-IL-6 Signaling Pathway Activation"]
    Hypothyroidism["Hypothyroidism"]
    Goiter["Goiter"]
    Hepatitis_C_Virus_Associated_Thyroid_Immune_Activation["Hepatitis C Virus-Associated Thyroid Immune Activation"]
    Cold_Intolerance["Cold Intolerance"]
    Weight_Gain["Weight Gain"]
    Thyrocyte_Antigen_Presentation["Thyrocyte Antigen Presentation"]
    Hashitoxicosis["Hashitoxicosis"]
    Anti_Thyroglobulin_Antibodies["Anti-Thyroglobulin Antibodies"]
    Selenium_Supplementation["Selenium Supplementation"]
    TSH["TSH"]
    Levothyroxine["Levothyroxine"]
    PTPN22["PTPN22"]
    Low_Dietary_Selenium_Intake["Low Dietary Selenium Intake"]
    Lymphocytic_Infiltration["Lymphocytic Infiltration"]
    Anti_TPO_Antibodies["Anti-TPO Antibodies"]
    Thyroidal_Oxidative_Stress_from_Selenoprotein_Insufficiency["Thyroidal Oxidative Stress from Selenoprotein Insufficiency"]
    Fatigue["Fatigue"]

    Thyroglobulin_Hyperiodination_and_Neoantigen_Formation --> Loss_of_Immune_Tolerance_to_Thyroid_Antigens
    Thyroidal_Oxidative_Stress_from_Selenoprotein_Insufficiency --> Loss_of_Immune_Tolerance_to_Thyroid_Antigens
    Impaired_Vitamin_D_Dependent_Immune_Tolerance --> Loss_of_Immune_Tolerance_to_Thyroid_Antigens
    Hepatitis_C_Virus_Associated_Thyroid_Immune_Activation --> Loss_of_Immune_Tolerance_to_Thyroid_Antigens
    Loss_of_Immune_Tolerance_to_Thyroid_Antigens --> Thyrocyte_Antigen_Presentation
    Loss_of_Immune_Tolerance_to_Thyroid_Antigens --> Lymphocytic_Infiltration
    Thyrocyte_Antigen_Presentation --> Lymphocytic_Infiltration
    Autoimmune_Thyroid_Destruction --> Thyroid_Hormone_Deficiency
    Autoimmune_Thyroid_Destruction --> Hashitoxicosis
    Lymphocytic_Infiltration --> Autoimmune_Thyroid_Destruction
    Lymphocytic_Infiltration --> Goiter
    NF_κB_IL_6_Signaling_Pathway_Activation --> Lymphocytic_Infiltration
    Thyroid_Hormone_Deficiency --> Hypothyroidism
    Vitamin_D_Deficiency --> Impaired_Vitamin_D_Dependent_Immune_Tolerance
    Selenium_Deficiency --> Thyroidal_Oxidative_Stress_from_Selenoprotein_Insufficiency
    Hypothyroidism --> Fatigue
    Hypothyroidism --> Weight_Gain
    Hypothyroidism --> Cold_Intolerance
    Hypothyroidism --> Dry_Skin
    Hypothyroidism --> Constipation
    Hypothyroidism --> Depression
    Iodine_Excess --> Thyroglobulin_Hyperiodination_and_Neoantigen_Formation
    Low_Dietary_Selenium_Intake --> Selenium_Deficiency
    Hepatitis_C_Virus_Infection --> Hepatitis_C_Virus_Associated_Thyroid_Immune_Activation
    Low_Vitamin_D_Intake_and_Cutaneous_Synthesis --> Vitamin_D_Deficiency
    Levothyroxine --> Thyroid_Hormone_Deficiency
    Selenium_Supplementation --> Autoimmune_Thyroid_Destruction
    Vitamin_D_Supplementation --> Autoimmune_Thyroid_Destruction
    Thyroid_Hormone_Deficiency -.-> TSH
    Thyroid_Hormone_Deficiency -.-> Free_T4
    Autoimmune_Thyroid_Destruction -.-> Anti_TPO_Antibodies
    Autoimmune_Thyroid_Destruction -.-> Anti_Thyroglobulin_Antibodies
    CTLA4 --> Loss_of_Immune_Tolerance_to_Thyroid_Antigens
    PTPN22 --> Loss_of_Immune_Tolerance_to_Thyroid_Antigens
    LAG3 --> Loss_of_Immune_Tolerance_to_Thyroid_Antigens

    style Selenium_Deficiency fill:#fef3c7
    style CTLA4 fill:#f3e8ff
    style Iodine_Excess fill:#dcfce7
    style Free_T4 fill:#e0e7ff
    style Autoimmune_Thyroid_Destruction fill:#dbeafe
    style Thyroglobulin_Hyperiodination_and_Neoantigen_Formation fill:#dbeafe
    style LAG3 fill:#f3e8ff
    style Hepatitis_C_Virus_Infection fill:#dcfce7
    style Depression fill:#fef3c7
    style Vitamin_D_Deficiency fill:#fef3c7
    style Loss_of_Immune_Tolerance_to_Thyroid_Antigens fill:#dbeafe
    style Dry_Skin fill:#fef3c7
    style Impaired_Vitamin_D_Dependent_Immune_Tolerance fill:#dbeafe
    style Low_Vitamin_D_Intake_and_Cutaneous_Synthesis fill:#dcfce7
    style Thyroid_Hormone_Deficiency fill:#dbeafe
    style Constipation fill:#fef3c7
    style Vitamin_D_Supplementation fill:#fce7f3
    style NF_κB_IL_6_Signaling_Pathway_Activation fill:#dbeafe
    style Hypothyroidism fill:#fef3c7
    style Goiter fill:#fef3c7
    style Hepatitis_C_Virus_Associated_Thyroid_Immune_Activation fill:#dbeafe
    style Cold_Intolerance fill:#fef3c7
    style Weight_Gain fill:#fef3c7
    style Thyrocyte_Antigen_Presentation fill:#dbeafe
    style Hashitoxicosis fill:#fef3c7
    style Anti_Thyroglobulin_Antibodies fill:#e0e7ff
    style Selenium_Supplementation fill:#fce7f3
    style TSH fill:#e0e7ff
    style Levothyroxine fill:#fce7f3
    style PTPN22 fill:#f3e8ff
    style Low_Dietary_Selenium_Intake fill:#dcfce7
    style Lymphocytic_Infiltration fill:#dbeafe
    style Anti_TPO_Antibodies fill:#e0e7ff
    style Thyroidal_Oxidative_Stress_from_Selenoprotein_Insufficiency fill:#dbeafe
    style Fatigue fill:#fef3c7
H

Hypotheses

Shared organ-specific autoimmune susceptibility - HLA class II haplotypes plus non-HLA loci such as PTPN22 - predisposes to both autoimmune gastritis and autoimmune thyroid disease, manifesting as thyrogastric polyautoimmunity rather than one condition causing the other.
PMID:34145262 (SUPPORT)
Source: HUMAN_CLINICAL
"We conduct a genome-wide association study meta-analysis in 2166 cases and 659,516 European controls from population-based biobanks and identify genome-wide significant signals in or near the PTPN22"
The PTPN22/HLA susceptibility architecture of pernicious anemia / autoimmune gastritis is shared with other organ-specific autoimmune diseases including autoimmune thyroid disease.
Y

Raw YAML

Show YAML
name: com_Autoimmune_Gastritis__Hashimotos_Thyroiditis
creation_date: '2026-07-01T00:00:00Z'
curation_status: CANDIDATE
notes: >-
  Thyrogastric syndrome: the frequent co-occurrence of autoimmune (atrophic)
  gastritis and autoimmune thyroid disease (Hashimoto thyroiditis) is the most
  characteristic polyautoimmune pairing for autoimmune gastritis, reflecting a
  shared organ-specific autoimmune susceptibility. Autoimmune gastritis also
  clusters with type 1 diabetes mellitus and vitiligo; those pairings could be
  captured as additional comorbidity entries.
disease_a:
  slug: Autoimmune_Gastritis
  preferred_term: Autoimmune Gastritis
  term:
    id: MONDO:0031014
    label: autoimmune gastritis
disease_b:
  slug: Hashimotos_Thyroiditis
  preferred_term: Hashimoto thyroiditis
  term:
    id: MONDO:0007699
    label: Hashimoto thyroiditis
directionality: BIDIRECTIONAL
literature_evidence:
- reference: PMID:31864909
  reference_title: "Thyro-entero-gastric autoimmunity: Pathophysiology and implications for patient management."
  supports: SUPPORT
  evidence_source: HUMAN_CLINICAL
  snippet: "autoimmune thyroid disorders, in particular Hashimoto's thyroiditis, may be frequently associated with other organ-specific, immune-mediated disorders, such as autoimmune atrophic gastritis or celiac disease."
  explanation: Establishes the frequent association of Hashimoto thyroiditis with autoimmune atrophic gastritis - the thyrogastric syndrome.
- reference: PMID:28102858
  reference_title: "Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients."
  supports: SUPPORT
  evidence_source: HUMAN_CLINICAL
  snippet: "prevalence of ~2% in the general population and up to 10% in patients with other autoimmune diseases, such as type I diabetes or autoimmune thyroid disease."
  explanation: Autoimmune gastritis prevalence rises to ~10% among patients with other autoimmune diseases, including autoimmune thyroid disease.
hypotheses:
- description: >-
    Shared organ-specific autoimmune susceptibility - HLA class II haplotypes plus
    non-HLA loci such as PTPN22 - predisposes to both autoimmune gastritis and
    autoimmune thyroid disease, manifesting as thyrogastric polyautoimmunity rather
    than one condition causing the other.
  evidence:
  - reference: PMID:34145262
    reference_title: "Genome-wide association study identifies five risk loci for pernicious anemia."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We conduct a genome-wide association study meta-analysis in 2166 cases and 659,516 European controls from population-based biobanks and identify genome-wide significant signals in or near the PTPN22"
    explanation: The PTPN22/HLA susceptibility architecture of pernicious anemia / autoimmune gastritis is shared with other organ-specific autoimmune diseases including autoimmune thyroid disease.
Source:GitHub