Renal Manifestations of Common Variable Immunodeficiency

Area of Science:

• Nephrology
• Immunology
• Pathology

Background:

• Common variable immunodeficiency (CVID) is a primary immunodeficiency affecting 1 in 25,000-50,000 individuals.
• Renal insufficiency occurs in approximately 2% of CVID patients, but renal biopsy data is scarce.
• This study analyzes renal biopsy findings in CVID patients to understand the pathophysiology of renal disease.

Purpose of the Study:

• To investigate the spectrum of renal pathology in patients with Common Variable Immunodeficiency (CVID).
• To determine the frequency and characteristics of kidney diseases associated with CVID.
• To establish potential links between CVID and specific renal biopsy findings.

Main Methods:

• Retrospective analysis of 27 renal biopsy specimens from 22 CVID patients.
• Utilized light, immunofluorescence, and electron microscopy for all biopsies.
• Performed specific immunohistochemistry and immunofluorescence for glomerulonephritis and tubulointerstitial nephritis subtyping.

Main Results:

• Immune-complex glomerulopathy was found in 54.5% of cases, predominantly membranous glomerulopathy (MGN).
• All MGN cases were negative for PLA2R, THSD7A, EXT1, and NELL1, but showed IgG1 subclass dominance and mesangial deposits.
• Chronic tubulointerstitial nephritis (TIN) was the second most common diagnosis (33%), characterized by tubulitis and T-cell infiltrates.

Conclusions:

• Membranous glomerulopathy and tubulointerstitial nephritis are the predominant renal pathologies in CVID patients.
• MGN in CVID patients differs from typical PLA2R-associated MGN, suggesting a distinct pathogenesis.
• CVID should be considered in young patients presenting with MGN or chronic TIN and a history of recurrent infections.