Effect of 51p1-related gene copy number (V1-69 locus) on production of hepatitis C-associated cryoglobulins.

Abstract

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.

• Authors: E H Sasso, P Ghillani, L Musset, J C Piette, P Cacoub
• Journal: Clinical and experimental immunology (Clin Exp Immunol) Vol. 123 Issue 1 Pg. 88-93 (Jan 2001) ISSN: 0009-9104 [Print] England
• PMID: 11168003 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cryoglobulins
• Genetic Markers
• Immunoglobulin Heavy Chains
• Immunoglobulin M
• Immunoglobulin Variable Region
• cryoglobulin M

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Cryoglobulins (analysis, biosynthesis, genetics)
• Female
• Gene Dosage
• Genes, Immunoglobulin
• Genetic Markers (immunology)
• Genotype
• Hepatitis C, Chronic (genetics, immunology)
• Humans
• Immunoglobulin Heavy Chains (biosynthesis, genetics)
• Immunoglobulin M (analysis, biosynthesis, genetics)
• Immunoglobulin Variable Region (biosynthesis, genetics)
• Male
• Middle Aged
• Phenotype