Diagnostic Utility of Galactose-Deficient Immunoglobulin A1 Immunostaining in the Differentiation of Lupus Nephritis and Immunoglobulin A Nephropathy

BACKGROUND: Renal biopsy plays an important role in the establishment of the diagnosis and the management of patients with lupus nephritis. Immunoglobulin A (IgA) nephropathy rarely has been reported in kidney biopsy of lupus patients. Lupus nephritis and IgA nephropathy can be readily diagnosed on renal biopsy when the classic patterns are present. However, atypical patterns can become a diagnostic challenge. Galactose-deficient IgA1 (Gd-IgA1) is a key element in the pathogenesis of primary IgA nephropathy. Glomerular Gd-IgA1 deposits, detected by immunofluorescent staining of KM-55 (a Gd-IgA1-specific monoclonal antibody), are consistently identified in the mesangium of IgA nephropathy but are significantly less or absent in lupus nephritis accompanied by significant IgA deposition. CASE PRESENTATION: Here we report the case of an 11-year-old girl who was recently diagnosed with systemic lupus erythematosus (SLE) and was found to have hematuria and proteinuria. Renal biopsy showed focal mesangial hypercellularity with IgA dominant, “full house” like pattern of mesangial deposition. The biopsy findings present a diagnostic dilemma with the differential diagnosis of IgA nephropathy versus lupus nephritis with atypical immunofluorescence, and IgA nephropathy is favored, in the absence of strong straining of C1q or C3, extraglomerular deposits, tissue antinuclear antibodies, and endothelial tubuloreticular inclusions. However, no detectable glomerular KM-55 staining was seen in the kidney biopsy. CONCLUSIONS: We demonstrate the unique diagnostic utility of immunostaining for KM-55 in a challenging kidney biopsy of an SLE patient with features suggestive of IgA nephropathy. The absence of KM-55 staining excludes IgA nephropathy, supporting a diagnosis of lupus nephritis with atypical immunofluorescence in this patient with SLE.