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A monoclonal V kappa l light chain responsible for incomplete proximal tubulopathy.
- Source :
-
American journal of kidney diseases : the official journal of the National Kidney Foundation [Am J Kidney Dis] 2003 Feb; Vol. 41 (2), pp. 497-504. - Publication Year :
- 2003
-
Abstract
- Calcium and phosphate metabolism abnormalities are frequent in myeloma patients and the role of renal lesions in such ionic perturbations may have been overlooked. The authors herein report the complete primary structure of a Bence Jones Vkappal light chain responsible for myeloma-associated proximal tubulopathy with increased phosphaturia. Plasma and serum biochemical evaluations indicated a proximal tubular dysfunction mainly manifested as tubular acidosis and phosphate loss. The study of a kidney biopsy showed interstitial and tubular lesions with numerous myeloma casts and peculiar features of the proximal tubular cells, which carried numerous phagolysosomal inclusions with occasional crystalline periodic striation. The nephrotoxic light chain primary structure was deduced from the bone marrow monoclonal plasma cells RNA. The kappal sequence was highly homologous to kappa chains previously characterized in patients with Fanconi syndrome. It was related to the Vkappal subgroup and was composed of a variable segment encoded by the O8/O18 germline gene rearranged to Jkappa4. The primary sequence presented unusual features restricted to the variable region, including substitutions of residues 28 and 31 in the complementary determining region 1 (CDR1) by amino acids of different charge. An unusual conformation of the kappal domain, likely resulting from somatic hypermutation, could alter the catabolism of the protein after its internalization and result in the tubular cell dysfunction. Comparison with Fanconi syndrome studies suggests that Vkappal Bence Jones proteins may damage proximal tubular cells to an extent varying according to light chain (LC) sequence and structure, either leading to crystal formation and Fanconi syndrome or inducing partial inhibition of proximal tubule function.<br /> (Copyright 2003 by the National Kidney Foundation, Inc.)
- Subjects :
- Amino Acid Sequence
Antibodies, Monoclonal blood
Antibodies, Monoclonal chemistry
Antibodies, Monoclonal genetics
Base Sequence
Fanconi Syndrome genetics
Fanconi Syndrome immunology
Fanconi Syndrome pathology
Female
Humans
Immunoglobulin Variable Region blood
Immunoglobulin Variable Region chemistry
Immunoglobulin Variable Region genetics
Immunoglobulin kappa-Chains blood
Immunoglobulin kappa-Chains chemistry
Immunoglobulin kappa-Chains genetics
Kidney Tubules, Proximal immunology
Molecular Sequence Data
Multiple Myeloma immunology
Multiple Myeloma pathology
Tumor Cells, Cultured
Antibodies, Monoclonal physiology
Immunoglobulin Variable Region physiology
Immunoglobulin kappa-Chains physiology
Kidney Tubules, Proximal pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1523-6838
- Volume :
- 41
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of kidney diseases : the official journal of the National Kidney Foundation
- Publication Type :
- Academic Journal
- Accession number :
- 12552516
- Full Text :
- https://doi.org/10.1053/ajkd.2003.50062