Immunoglobulin G4-related pathologic features in inflammatory neuropathies

Area of Science:

• Neurology
• Immunology
• Pathology

Background:

• Inflammatory peripheral neuropathies represent a heterogeneous group of disorders.
• The role of immunoglobulin G4 (IgG4) in these conditions is not fully understood.
• IgG4-related disease is increasingly recognized, necessitating investigation into its presence in other inflammatory conditions.

Purpose of the Study:

• To investigate the pathologic significance of immunoglobulin G4 (IgG4) in patients presenting with inflammatory peripheral neuropathy.
• To determine the prevalence of elevated serum IgG4 levels and IgG4-positive plasma cell infiltration in this patient cohort.

Main Methods:

• Clinicopathologic examination of 149 patients with peripheral neuropathy and inflammatory cell clusters in sural nerve biopsies.
• Assessment of serum IgG4 levels in all patients.
• Histopathologic analysis of nerve biopsy specimens for IgG4-positive plasma cells, vasculitis, and fibrosis.

Main Results:

• Elevated serum IgG4 levels were observed in 35 patients, and IgG4-positive plasma cell infiltration in 29 patients.
• Among 44 patients with either elevated IgG4 or infiltration, diagnoses included microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis.
• Vasculitis was present in 77% of these 44 patients; axonal degeneration was common, and epineurial fibrosis correlated significantly with IgG4-positive cell infiltration (p < 0.01).

Conclusions:

• A subgroup of patients with inflammatory neuropathy, particularly those with primary systemic vasculitis like microscopic polyangiitis, exhibit elevated serum IgG4 and IgG4-positive plasma cell infiltration.
• Epineurial IgG4-positive plasma cell infiltration is associated with the degree of epineurial fibrosis in these patients.
• These findings suggest a potential role for IgG4 in the pathogenesis of certain inflammatory neuropathies.