Effect of 51p1-related gene copy number (V1-69 locus) on production of hepatitis C-associated cryoglobulins.
Monoclonal IgM in type II mixed cryoglobulins (MC) preferentially use 51p1-related immunoglobulin VH genes. In normal preimmune B lymphocytes, 51p1-related gene expression is proportional to the germ-line gene dosage, which can be 0-4. To determine whether 51p1-related gene dosage influences the occurrence of type II MC or the VH gene bias in cryoglobulin IgM, we studied 47 patients chronically infected with hepatitis C virus (HCV), 24 MC+, 23 MC-. By Western analysis, 11 cryoprecipitate IgM (46%) were detected by G6 (a marker for 51p1-related gene products), eight (33%) by Staphylococcal Protein A (a VH3 family marker), and five (21%) by neither, indicating a 23-fold bias favouring 51p1-related genes. All 11 MC+, G6+ patients possessed > or = 1 copy of a 51p1-related gene; nine of the 36 others had none. The mean copy number of 51p1-related genes was greater in MC+ than MC- patients, and in MC+, G6+ patients versus the 36 others (P < 0.04), but significant differences were not seen in analyses restricted to patients with > or = 1 copy of a 51p1-related gene. We conclude that when a 51p1-related gene is present, a strong bias favours G6+ IgM in HCV-associated type II MC, but this bias is not greatly increased by a high dosage of 51p1-related genes. Furthermore, patients lacking 51p1-related genes also produce MC, but with G6- IgM.
Sasso
E H
EH
Department of Medicine, Division of Rheumatology, University of Washington, Seattle, WA, USA. esasso@u.washington.edu
Ghillani
P
P
Musset
L
L
Piette
J C
JC
Cacoub
P
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003450:Cryoglobulins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D005803:Genes, Immunoglobulin; D005819:Genetic Markers / Q000276:immunology; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D007075:Immunoglobulin M / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D003450:Cryoglobulins; D005819:Genetic Markers; D007143:Immunoglobulin Heavy Chains; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region; C043325:cryoglobulin M