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Nodular Glomerulosclerosis with Deposition of Monoclonal Immunoglobulin Heavy Chains Lacking C_H1

BRUNO MOULIN^*, SOPHIE DERET^¶, XAVIER MARIETTE^||, OLIVIER KOURILSKY, HIROKAZU IMAI^**, LUC DUPOUET^§, LUC MARCELLIN, ISABELLE KOLB^*, PIERRE AUCOUTURIER^¶, JEAN-CLAUDE BROUET^¶, PIERRE M. RONCO^# and BÉATRICE MOUGENOT^#

^* Department of Nephrology University Hospital, Strasbourg, France
Department of Pathology, University Hospital, Strasbourg, France
Renal Divisions, Evry Hospital Paris, France
^§ Renal Divisions, Chartres Hospital; Paris, France
^|| Department of Clinical Immunology, Saint-Louis Hospital, and Institut National de la Santé et de la Recherche Médicale Paris, France
^¶ Renal Divisions, and Institut National de la Santé et de la Recherche Médicale U 25 Necker and Tenon Hospitals, Assistance Publique-Hôpitaux de Paris, Paris, France
^# Renal Divisions, and Institut National de la Santé et de la Recherche Médicale U489, Necker and Tenon Hospitals, Assistance Publique-Hôpitaux de Paris, Paris, France
^** Third Department of Internal Medicine, Akita University School of Medicine, Akita, Japan.

Correspondence to Dr. Pierre Ronco, Renal Division and Institut National de la Santé et de la Recherche Médicale U489, Hôpital Tenon, 4 Rue de la Chine 75020 Paris, France. Phone: 33 1 56 01 66 39; Fax: 33 1 56 01 69 99; E-mail: pierre.ronco{at}tnn.ap-hop-paris.fr

Abstract. 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 1 heavy chains lacking C_H1 epitopes, but without light chains. Two different patterns were observed in the serum. First, patients 1 and 2 had a circulating monoclonal IgG containing a short 1 heavy chain lacking C_H1 epitopes, with an apparent molecular weight of 40 kD consistent with a complete C_H1 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 IgG1 with an apparently normal, nondeleted heavy chain subunit, but serum fractionation followed by immunoblotting revealed an isolated monoclonal 1 chain lacking C_H1 epitopes. These data strongly suggest that renal deposition of a C_H1-deleted heavy chain circulating in low amounts in the serum as a free unassembled subunit is a major feature of HCDD. The C_H1 deletion is most likely responsible for the premature secretion in blood of the heavy chain by a clone of plasma cells.

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