Nodular glomerulosclerosis with deposition of monoclonal immunoglobulin heavy chains lacking C(H)1

• Published in: Journal of the American Society of Nephrology Vol. 10; no. 3; pp. 519 - 528
• Main Authors: Moulin, B, Deret, S, Mariette, X, Kourilsky, O, Imai, H, Dupouet, L, Marcellin, L, Kolb, I, Aucouturier, P, Brouet, J C, Ronco, P M, Mougenot, B
• Format: Journal Article
• Language: English
• Published: United States 01.03.1999
• Subjects: Adult; Aged; Basement Membrane - ultrastructure; Biopsy, Needle; Bone Marrow - pathology; Female; Glomerular Mesangium - ultrastructure; Glomerulosclerosis, Focal Segmental - blood; Glomerulosclerosis, Focal Segmental - immunology; Glomerulosclerosis, Focal Segmental - pathology; Glomerulosclerosis, Focal Segmental - urine; Heavy Chain Disease - complications; Heavy Chain Disease - pathology; Humans; Immunoblotting; Immunoglobulin A - analysis; Immunoglobulin G - analysis; Immunohistochemistry; Immunoproliferative Small Intestinal Disease - complications; Immunoproliferative Small Intestinal Disease - pathology; Male; Microscopy, Electron; Middle Aged; Sensitivity and Specificity
• ISSN: 1046-6673

The objective of this study was to further characterize the clinical and immunopathologic features of heavy chain deposition disease (HCDD), a recently described entity. Four patients were diagnosed as having HCDD on a kidney biopsy. All presented with nodular glomerulosclerosis with deposition of gamma1 heavy chains lacking CH1 epitopes, but without light chains. Two different patterns were observed in the serum. First, patients 1 and 2 had a circulating monoclonal IgGlambda containing a short gamma1 heavy chain lacking CH1 epitopes, with an apparent molecular weight of 40 kD consistent with a complete CH1 deletion. Biosynthetic experiments also showed that the deleted heavy chain was produced in excess compared with light chains, and was secreted in vitro together with half Ig molecules, although these abnormal components were not detected by Western blot analysis of whole serum. Second, patients 3 and 4 had a circulating monoclonal IgG1lambda with an apparently normal, nondeleted heavy chain subunit, but serum fractionation followed by immunoblotting revealed an isolated monoclonal gamma1 chain lacking CH1 epitopes. These data strongly suggest that renal deposition of a CH1-deleted heavy chain circulating in low amounts in the serum as a free unassembled subunit is a major feature of HCDD. The CH1 deletion is most likely responsible for the premature secretion in blood of the heavy chain by a clone of plasma cells.