Chronic Inflammatory Demyelinating Polyneuropathy

🏷

Classifications

Harrison's Chapter

⚙

Pathophysiology

3

T Cell-Mediated Demyelination

CD4+ and CD8+ T cells infiltrate peripheral nerves and contribute to demyelination. T cells recognize myelin antigens and produce inflammatory cytokines that damage Schwann cells.

CD4+ T Cell link CD8+ T Cell link

Adaptive Immune Response link

Show evidence (1 reference)

PMID:37356965 PARTIAL

"Autoimmune neuropathies are a heterogeneous group of rare and disabling diseases in which the immune system is thought to target antigens in the peripheral nervous system: they usually respond to immune therapies."

This pathology review confirms that CIDP involves immune-mediated targeting of peripheral nerve antigens, supporting the role of adaptive immunity including T cell responses in disease pathogenesis.

Antibody and Complement-Mediated Damage

Autoantibodies against myelin proteins and nodal/paranodal antigens (neurofascin, contactin-1) contribute to demyelination. Complement deposition amplifies nerve damage.

Complement Activation link Immunoglobulin Production link

Show evidence (2 references)

PMID:35378684 SUPPORT

"The complement system appears to play a role in promoting macrophage-mediated demyelination."

This review establishes the role of complement activation in CIDP pathogenesis, linking complement to the amplification of macrophage-mediated nerve damage.

PMID:36346134 SUPPORT

"Besides IgG4, subclass IgG3 was detected and associated with complement binding and cytotoxic effects in vitro."

Experimental evidence showing that IgG3 subclass antibodies activate complement, demonstrating complement-mediated pathogenic mechanisms in autoantibody-positive CIDP.

Macrophage-Mediated Myelin Stripping

Activated macrophages invade nerve fibers and actively strip myelin from axons, causing segmental demyelination visible on nerve biopsy.

Macrophage link

Inflammatory Response link

Show evidence (2 references)

PMID:37356965 PARTIAL

"In contrast, the mechanisms of demyelination of other dysimmune neuropathies induced by macrophages are unexplained, as no antibodies have been identified in such cases."

This pathology review acknowledges macrophage-induced demyelination as a distinct mechanism in CIDP, occurring even in cases without identified autoantibodies, supporting the role of innate immune responses independent of antibody-mediated damage.

PMID:36645654 PARTIAL

"The proposed mechanisms of action of IVIg that can mediate its therapeutic effects are reviewed. These include anti-idiotypic interactions, inhibition of neonatal Fc receptors (FcRn), anti-complement activity, upregulation of inhibitory FcγRIIB receptors, and downregulation of macrophage activation."

IVIg therapy works in part by downregulating macrophage activation, providing indirect evidence that macrophages play a central pathogenic role in CIDP that can be therapeutically targeted.

●

Phenotypes

4

Limbs(1) Nervous System(2) Constitutional(1)

Limbs 1

Progressive Weakness VERY_FREQUENT Limb muscle weakness (HP:0003690)

Symmetric, proximal and distal

Nervous System 2

Areflexia VERY_FREQUENT Areflexia (HP:0001284)

Sensory Loss FREQUENT Sensory neuropathy (HP:0000763)

Show evidence (1 reference)

PMID:38330421 SUPPORT

"Sensory CIDP was diagnosed when two inclusion criteria are met: 1) acquired, chronic progressive or relapsing symmetrical or asymmetrical sensory polyneuropathy that had progressed for >2 months."

This clinical study establishes sensory polyneuropathy as a diagnostic criterion and key phenotype of sensory CIDP variant, demonstrating that sensory loss is a prominent and treatable feature in CIDP.

Constitutional 1

Fatigue FREQUENT Fatigue (HP:0012378)

💊

Treatments

4

IVIG

First-line therapy for most patients.

Corticosteroids

Alternative first-line therapy.

Plasmapheresis

For refractory cases or acute exacerbations.

Rituximab

For antibody-positive refractory cases.

🔬

Biochemical Markers

3

CSF Protein (Elevated)

Context: Without pleocytosis

Anti-Neurofascin Antibodies (Variable)

Context: Associated with specific CIDP subtype

Anti-Contactin-1 Antibodies (Variable)

Context: Associated with specific CIDP subtype

{ }

Source YAML

click to show

name: Chronic Inflammatory Demyelinating Polyneuropathy
creation_date: '2025-12-19T01:12:52Z'
updated_date: '2026-02-17T21:53:14Z'
category: Autoimmune
parents:
- Autoimmune Disease
- Peripheral Neuropathy
disease_term:
  preferred_term: Chronic Inflammatory Demyelinating Polyradiculoneuropathy
  term:
    id: MONDO:0006702
    label: chronic inflammatory demyelinating polyradiculoneuropathy
description: >-
  A chronic acquired immune-mediated neuropathy characterized by progressive
  or relapsing-remitting symmetric proximal and distal weakness with sensory
  involvement. Distinguished from GBS by duration greater than 8 weeks and
  chronic course.
pathophysiology:
- name: T Cell-Mediated Demyelination
  description: >-
    CD4+ and CD8+ T cells infiltrate peripheral nerves and contribute to
    demyelination. T cells recognize myelin antigens and produce inflammatory
    cytokines that damage Schwann cells.
  cell_types:
  - preferred_term: CD4+ T Cell
    term:
      id: CL:0000624
      label: CD4-positive, alpha-beta T cell
  - preferred_term: CD8+ T Cell
    term:
      id: CL:0000625
      label: CD8-positive, alpha-beta T cell
  biological_processes:
  - preferred_term: Adaptive Immune Response
    term:
      id: GO:0002250
      label: adaptive immune response
  evidence:
  - reference: PMID:37356965
    supports: PARTIAL
    snippet: >-
      Autoimmune neuropathies are a heterogeneous group of rare and disabling diseases
      in which the immune system is thought to target antigens in the peripheral
      nervous system: they usually respond to immune therapies.
    explanation: >-
      This pathology review confirms that CIDP involves immune-mediated targeting
      of peripheral nerve antigens, supporting the role of adaptive immunity including
      T cell responses in disease pathogenesis.
- name: Antibody and Complement-Mediated Damage
  description: >-
    Autoantibodies against myelin proteins and nodal/paranodal antigens
    (neurofascin, contactin-1) contribute to demyelination. Complement
    deposition amplifies nerve damage.
  biological_processes:
  - preferred_term: Complement Activation
    term:
      id: GO:0006956
      label: complement activation
  - preferred_term: Immunoglobulin Production
    term:
      id: GO:0002377
      label: immunoglobulin production
  evidence:
  - reference: PMID:35378684
    supports: SUPPORT
    snippet: >-
      The complement system appears to play a role in promoting macrophage-mediated
      demyelination.
    explanation: >-
      This review establishes the role of complement activation in CIDP pathogenesis,
      linking complement to the amplification of macrophage-mediated nerve damage.
  - reference: PMID:36346134
    supports: SUPPORT
    snippet: >-
      Besides IgG4, subclass IgG3 was detected and associated with complement binding
      and cytotoxic effects in vitro.
    explanation: >-
      Experimental evidence showing that IgG3 subclass antibodies activate complement,
      demonstrating complement-mediated pathogenic mechanisms in autoantibody-positive
      CIDP.
- name: Macrophage-Mediated Myelin Stripping
  description: >-
    Activated macrophages invade nerve fibers and actively strip myelin from
    axons, causing segmental demyelination visible on nerve biopsy.
  cell_types:
  - preferred_term: Macrophage
    term:
      id: CL:0000235
      label: macrophage
  biological_processes:
  - preferred_term: Inflammatory Response
    term:
      id: GO:0006954
      label: inflammatory response
  evidence:
  - reference: PMID:37356965
    supports: PARTIAL
    snippet: >-
      In contrast, the mechanisms of demyelination of other dysimmune neuropathies
      induced by macrophages are unexplained, as no antibodies have been identified
      in such cases.
    explanation: >-
      This pathology review acknowledges macrophage-induced demyelination as a distinct
      mechanism in CIDP, occurring even in cases without identified autoantibodies,
      supporting the role of innate immune responses independent of antibody-mediated
      damage.
  - reference: PMID:36645654
    supports: PARTIAL
    snippet: >-
      The proposed mechanisms of action of IVIg that can mediate its therapeutic effects
      are reviewed. These include anti-idiotypic interactions, inhibition of neonatal
      Fc
      receptors (FcRn), anti-complement activity, upregulation of inhibitory FcγRIIB
      receptors, and downregulation of macrophage activation.
    explanation: >-
      IVIg therapy works in part by downregulating macrophage activation, providing
      indirect
      evidence that macrophages play a central pathogenic role in CIDP that can be
      therapeutically
      targeted.
phenotypes:
- name: Progressive Weakness
  category: Neurological
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Limb Muscle Weakness
    term:
      id: HP:0003690
      label: Limb muscle weakness
  notes: Symmetric, proximal and distal
- name: Areflexia
  category: Neurological
  frequency: VERY_FREQUENT
  phenotype_term:
    preferred_term: Areflexia
    term:
      id: HP:0001284
      label: Areflexia
- name: Sensory Loss
  category: Neurological
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Peripheral Sensory Neuropathy
    term:
      id: HP:0000763
      label: Sensory neuropathy
  evidence:
  - reference: PMID:38330421
    supports: SUPPORT
    snippet: >-
      Sensory CIDP was diagnosed when two inclusion criteria are met: 1) acquired,
      chronic progressive or relapsing symmetrical or asymmetrical sensory polyneuropathy
      that had progressed for >2 months.
    explanation: >-
      This clinical study establishes sensory polyneuropathy as a diagnostic criterion
      and key phenotype of sensory CIDP variant, demonstrating that sensory loss is
      a
      prominent and treatable feature in CIDP.
- name: Fatigue
  category: Systemic
  frequency: FREQUENT
  phenotype_term:
    preferred_term: Fatigue
    term:
      id: HP:0012378
      label: Fatigue
biochemical:
- name: CSF Protein
  presence: Elevated
  context: Without pleocytosis
- name: Anti-Neurofascin Antibodies
  presence: Variable
  context: Associated with specific CIDP subtype
- name: Anti-Contactin-1 Antibodies
  presence: Variable
  context: Associated with specific CIDP subtype
treatments:
- name: IVIG
  description: First-line therapy for most patients.
- name: Corticosteroids
  description: Alternative first-line therapy.
- name: Plasmapheresis
  description: For refractory cases or acute exacerbations.
- name: Rituximab
  description: For antibody-positive refractory cases.
classifications:
  harrisons_chapter:
  - classification_value: nervous system disorder
  - classification_value: neuromuscular disease
  - classification_value: autoimmune disease
references:
- reference: DOI:10.1111/bpa.13184
  title: Pathology explains various mechanisms of auto‐immune inflammatory
    peripheral neuropathies
  findings: []
- reference: DOI:10.3389/fimmu.2024.1475478
  title: 'Case report: target antigen and subclass switch in a patient with autoimmune
    nodopathy'
  findings: []
- reference: DOI:10.3389/fimmu.2025.1575464
  title: A pathophysiological and mechanistic review of chronic inflammatory
    demyelinating polyradiculoneuropathy therapy
  findings: []
- reference: DOI:10.69622/28457924.v1
  title: Biomarker and pathogenic study of immune-mediated neuropathies
  findings: []