Association between EcoRI fragment-length polymorphism of the immunoglobulin lambda variable 8 (IGLV8) gene family with rheumatoid arthritis and systemic lupus erythematosus

Abstract

The human immunoglobulin lambda variable 8 (IGLV8) subgroup is a gene family containing three members, one of them included in a monomorphic 3.7-kb EcoRI genomic fragment located at the major lambda variable locus on chromosome 22q11.1 (gene IGLV8a, EMBL accession No. Z73650) at 100% frequency in the normal urban population. The second is a polymorphic RFLP allele included in a 6.0-kb EcoRI fragment at 10% frequency, and the third is located in a monomorphic 8.0-kb EcoRI fragment at 100% frequency, the last being translocated to chromosome 8q11.2 and considered to be an orphan gene. Our Southern blot-EcoRI-RFLP studies in normal individuals and in patients with rheumatoid arthritis (RA) or with systemic lupus erythematosus (SLE), using a specific probe for the IGLV8 gene family (probe pVL8, EMBL accession No. X75424), have revealed the two monomorphic genomic fragments containing the IGLV8 genes, i.e., the 3.7-kb fragment from chromosome 22q11.1 and the 8.0-kb fragment from 8q11.2, both occurring at 100% frequency (103 normal individuals, 48 RA and 28 SLE patients analyzed), but absence of the 6.0-kb IGLV8 polymorphic RFLP allele in all RA or SLE patients. As expected, the frequency of the 6.0-kb allele among the normal individuals was 10%. These findings suggest an association between the absence of the 6.0-kb EcoRI fragment and rheumatoid arthritis and systemic lupus erythematosus. The human immunoglobulin lambda light chains contribute about 40% to the functional serum antibodies, indicating the important role played by these chains in the antibody response (1). The immunoglobulin lambda variable (IGLV) locus extends about 800 kb on chromosome 22q11.1-11.2 and has been mapped and fully sequenced by contig methodology locating all the known functional V-lambda genes and pseudogenes (2-5).We know the positions of about 70 germline V-lambda sequences of which 30-33 are functional V-lambda genes distributed into 11 IGLV gene families (IGLV1-

Genetics of Behcet disease inside and outside the MHC

“…There are 18 IGL genes within 100 kb from D22S0104i , and the nearest gene is IGLV1-40 (IGL variable 1–40) located 1.4 kb centromeric of D22S0104i . Previous studies have shown that the IGL locus or genes polymorphisms are associated with autoimmune disorders 38 39. In addition, an association between BD and elevations of some immunoglobulins has been noted 40–43…”

Immunoglobulin V‐Lambda Transcription Profiling of Systemic Lupus Erythematosus Patients Reveals Biased Usage of Genes Located Near the Jλ–Cλ Segments

“…Using RFLP of the IGLV8 gene segment, it was also possible to differentiate patients with SLE or rheumatoid arthritis from NIs [13].…”

“…Each IGLV gene is flanked by Eco RI restriction sites. Southern‐blot studies with genomic DNA from normal individuals (NIs) and patients with autoimmune diseases using a probe specific for the IGLV8 subgroup have revealed association between Eco RI–restriction fragment length polymorphism (RFLP) and manifestation of SLE or rheumatoid arthritis [13].…”