Atypical Plasmacytic Proliferation in a Case of C3 Glomerulopathy

Abstract

An 11-year-old Hispanic female underwent evaluation of asymptomatic proteinuria and hematuria. The patient denied fever, edema, and gross hematuria. Urinalysis showed mild proteinuria, and a urine microscopic examination revealed red blood cells. Screening tests for glomerulonephritis revealed a low C3 and negative ANA, ASO, DNAse-B, and ANCA. Histological examination of a renal biopsy specimen showed glomeruli with endocapillary proliferation, a predominant C3 deposition in the capillary loops by immunofluorescence, and electron dense deposits in the mesangium, paramesangium, and capillary walls by electron microscopy consistent with a diagnosis of C3 glomerulopathy. An interstitial plasmacytosis was also present with focal clustering of plasma cells, which were found to be kappa light chain restricted by in situ hybridization suggestive of a clonal proliferation. One can speculate that these plasma cells may be directly responsible for the renal pathology that was seen.

The role of the alternative pathway of complement activation in glomerular diseases

“…C3Nef frequently coexists with anti-CFH, possibly having a synergistic effect on AP dysregulation in plasma. In a single report, anti-CFH was also associated with monoclonal Ig (35% cases in the small group of 17 patients), which is in line with previous reports of monoclonal Ig pathogenic involvement in C3G [82,83,99].…”

“…Moreover, studies have shown that iC3b is the main constituent of the dense deposits in the GBM. Both CFI and CFH are essential for C3b cleavage to iC3b, but the abnormalities of CFH, not CFI are responsible for the disease occurrence [9,83,87]. This was demonstrated in an animal model, where CFH-deficient mice, which were also deficient in factor I, did not develop DDD but showed C3 mesangial deposition instead [86].…”

“…C3GN, on the other hand, is characterized by subendothelial, mesangial and in some cases subepithelial C3 deposits on EM. On the light microscopy (LM), 71% cases of C3GN show membranoproliferative pattern of injury, though mesangial proliferation, crescent formation, and glomerular sclerosis may also occur [7,8,10,62,67,82,83].…”

“…Some authors are seeking the answer in the frequent prevalence of monoclonal Ig deposition along with C3 and high frequency of plasma monoclonal Ig in C3G patients (approximately 31% of cases diagnosed with C3GN and 71% of DDD cases) [93,94]. An assumption that monoclonal Ig acts as autoantibody activating the AP has been made [82,83]. Using in situ hybridization, Elfituri et al found monoclonal kappa light chain plasma cells infiltrating the glomeruli of an 11-year-old C3GN patient, who had no monoclonal Ig in plasma and normal serum and urine electrophoresis pattern.…”

“…Using in situ hybridization, Elfituri et al found monoclonal kappa light chain plasma cells infiltrating the glomeruli of an 11-year-old C3GN patient, who had no monoclonal Ig in plasma and normal serum and urine electrophoresis pattern. Based on these findings, the authors hypothesized that monoclonal Ig might be the direct cause of C3 deposition [83].…”