IgA Nephropathy and Atypical Anti-GBM Disease: A Rare Dual Pathology in a Pediatric Rapidly Progressive Glomerulonephritis

Abstract

Introduction: Anti-GBM nephritis in the pediatric age group is exceedingly rare with concurrent additional pathologies being even rarer. Tissue diagnosis requires a combination of crescentic histomorphology, immunofluorescence showing “Paint brush stroke” pattern of linear IgG or rarely IgA and serum anti-GBM antibodies subject to the disease course and treatment. The authors describe one such case with a dual pathology involving IgA nephropathy and atypical anti-GBM disease. Case presentation: A thirteen-year-old girl presenting with features of rapidly progressive glomerulonephritis underwent a renal biopsy showing a mesangioproliferative histology with crescents and an immunofluorescence pattern indicating a dual pathology of IgA Nephropathy and Anti GBM Nephritis. Additional ancillary testing including staining for IgG subclasses and galactose deficient IgA (KM55) helped to confirm the diagnosis. She responded to steroid pulses and plasma exchange therapy, was off dialysis after 8 weeks with serum creatinine of 1.5 mg/dl however remains proteinuric at last follow up. Conclusion: Concurrent Anti-GBM nephritis and IgA nephropathy is a rare occurrence and possibly arises from a complex interaction between the anti-GBM antibodies and the basement membrane unmasking the antigens for IgA antibodies. Additional newer techniques like immunofluorescence for KM 55 are helpful in establishing the dual pathology.

Clinical Profile and Renal Survival of Anti-Glomerular Basement Membrane Disease Patients: A Retrospective Case Series from Northern India

“…The previous studies have shown mixed picture with small studies reporting poor prognosis [7], while a large study reported better prognosis and outcomes of double-positive patients [12]. In 2 (14.2%) of our renal biopsied patients have concomitant mesangial IgA positivity along with linear IgG; this mesangial IgA positivity along with linear IgG positivity was also seen in 4% patients of the Zahir et al cohort and multiple other studies also [13, 18, 19].…”

“…Nine (60%) patients were in the 6th decade of their life, and rest in 2nd and 3rd decades. The median duration of symptoms onset to nephrologist opinion was 15 (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23) days. The extrarenal manifestations were seen in the respiratory system [3 (20%)], otorhinolaryngological system (2 [3.3%]), and neurological system [1 (6%)].…”

Atypical anti-glomerular basement membrane disease with membranous hyperplasia: diagnostic challenges and treatment variability

“… 43/F [ 23 ] Focal crescents and endocapillary hypercellularity IgG (+); IgA (-); IgM (-); C3 (-); C4 (-); C1q (-); IgG1 (+);IgG4 (+); IgG2 (-);IgG3 (-); kappa (+); and lambda (+). linear deposition Negative Some FPE 13/F [ 24 ] Mesangial proliferation, focal crescents, some globally or segmentally sclerosed glomeruli IgG (+); IgA (+); IgM (-); C3 (+);C1q (-); IgG1 (+);IgG4 (+);kappa (+); and lambda (+). linear deposition Negative NA 4/F [ 25 ] Subtle segmental scars, segmental endocapillary hypercellularity, and cellular crescent IgG (+);IgA (-); IgM (-); C3 (-); C1q (-).…”

Coexistence of anti-glomerular basement membrane disease and IgA nephropathy: an illustrative case and comprehensive literature review

“…Pathogenesis of IgAN is characterized by IgA-containing immune complexes passing through the glomerular capillary walls and depositing extensively in the mesangium [ 11 ]. It has been suggested that epitopes are isolated under normal circumstances and exposed following some physicochemical disruption, which then allows the initiation of immune response [ 17 ]. There was one hypothesis that IgA-related immune complexes might promote immunologic and inflammatory activities, leading to conformational changes and exposure of GBM antigens resulting in the development of anti-GBM autoantibodies [ 22 ].…”