A Peculiar Case of Glomerular IgG Deposits in a Patient with Common Variable Immunodeficiency

Introduction: Immunoglobulin (Ig) therapy, based on the administration of human plasma-derived Ig, is used to treat various autoimmune diseases and immunodeficiencies, like the common variable immunodeficiency (CVID), which is characterized by lymphocytic abnormalities and defective antibody production, with resulting opportunistic infections and, in some cases, autoimmune disorders. Case Description: A 50-year-old female with CKD G3a presented with increasing proteinuria (UPCR 1.5 g/g). Eighteen years earlier, she underwent an autologous hematopoietic stem cell transplantation (HSCT) to treat severe refractory systemic lupus erythematosus, with no evidence of lupus activity thereafter. Six years following HSCT she was diagnosed with CVID and started weekly immunoglobulin replacement therapy (IRT). Kidney biopsy showed frequent glomerular capillary wall duplication and mesangial expansion with hypercellularity, focal segmental glomerulosclerosis, and mild tubulointerstitial scarring. Immunofluorescence revealed 3+ granular mesangial and glomerular capillary wall staining for IgG, kappa and lambda light chains. Staining for IgG subclasses was positive for IgG1 (2+) and IgG2 (1+) [Fig.1]. Electron microscopy demonstrated extensive glomerular basement membranes remodeling, and subendothelial, intramembranous and mesangial electron-dense deposits [Fig.2]. Discussion: The biopsy showed chronic microangiopathic features, compatible with the prior history of HSCT, and findings consistent with immune-complex glomerulonephritis, which is rarely reported in the setting of CVID. Of interest, the patient had B cell depletion and received IRT. Thus, the circulating Ig were primarily of exogenous origin, and were conceivably the main component of the observed glomerular immune deposits. Further studies will be necessary to understand the potential pathogenic role of long-term Ig therapy in the development of glomerular diseases.