Possible Deletion of a Developmentally Regulated Heavy-Chain Variable Region Gene in Autoimmune Diseases

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 87; no. 20; pp. 7907 - 7911
• Main Authors: Yang, Pei-Ming, Olsen, Nancy J., Siminovitch, Katherine A., Olee, Tsaiwei, Kozin, Franklin, Carson, Dennis A., Chen, Pojen P.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01.10.1990; National Acad Sciences
• Subjects: 550201 - Biochemistry- Tracer Techniques; Antibodies; Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - immunology; Autoantibodies; Autoimmune diseases; Autoimmune Diseases - genetics; Autoimmune Diseases - immunology; Autoimmunity (experimental aspects and models); B lymphocytes; BASIC BIOLOGICAL SCIENCES; Biological and medical sciences; CHROMOSOMAL ABERRATIONS; Chromosome Deletion; DISEASES; DNA; DNA - blood; DNA - isolation & purification; DNA HYBRIDIZATION; DNA probes; Enzymes; ETIOLOGY; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Genes, Immunoglobulin; Genetic hybridization; Genetic loci; Genomic Library; Genotypes; Humans; HYBRIDIZATION; IMMUNE SYSTEM DISEASES; Immunoglobulin Heavy Chains - genetics; Immunoglobulin Variable Region - genetics; Leukocytes - immunology; LUPUS; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - immunology; MUTATIONS; NUCLEIC ACIDS; OLIGONUCLEOTIDES; ONTOGENESIS; ORGANIC COMPOUNDS; PATIENTS; Reference Values; Restriction Mapping; RFLPS; RHEUMATIC DISEASES; SKELETAL DISEASES; Human; Restriction fragment length polymorphism; Gene; Rheumatoid arthritis; Autoimmune disease; Molecular probe; Mutation; Southern blotting
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.87.20.7907

Several autoantibody-associated variable region (V) genes are preferentially expressed during early ontogenic development, suggesting strongly that they are of developmental and physiological importance. As such, it is possible that polymorphisms in one or more of these genes may alter susceptibility to autoimmune disease. We have searched extensively for a probe related to a developmentally regulated V gene that has the power to differentiate among highly homologous V genes in human populations. Using such a probe (i.e.,Humhv3005/P1) related to both anti-DNA and anti-IgG auto-antibodies, we studied restriction fragment length polymorphisms in patients with rheumatoid arthritis and systemic lupus erythematosus and found an apparent heavy-chain V (VH) gene deletion that was nearly restricted to the autoimmune patients. These data suggest that deletions of physiologically important VHgenes may increase the risk of autoimmunity through indirect effects on the development and homeostasis of the B-cell repertoire.