Polymorphism in the Iα1 Germ-Line Transcript Regulatory Region and IgA Productivity in Patients with IgA Nephropathy

• Published in: The Journal of immunology (1950) 1998-05, Vol.160 (10), p.4936-4942
• Main Authors: Yano, Naohiro, Asakura, Kumiko, Endoh, Masayuki, Abe, Yoshifumi, Nomoto, Yasuo, Sakai, Hideto, Kurokawa, Kiyoshi, Tsukamoto, Hideo
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.10.4936

Enhanced in vivo and in vitro production of IgA has been reported in patients with IgA nephropathy (IgAN) and their family members. It is generally considered that IgA1 is a prominent subclass of IgA in IgAN. Although genetic mechanisms of IgA class switch recombination in IgAN have been studied enthusiastically, the critical factors that induce IgA1-specific class switching in IgAN have yet to be elucidated. A large body of data indicates that the germ-line transcript of Ig constant region (CH) genes that precedes actual class switching has regulatory effects on class switch recombination. To analyze structural abnormalities in the Iα1 germ-line transcript regulatory gene, a region about 1000 bp long located upstream of Iα1 exons was surveyed by the PCR-single strand conformation polymorphism method, and the polymorphism detected was confirmed by subsequent DNA sequencing. Three hot spots for point mutation were detected upstream of the promoter region of the Iα1 germ-line transcript, and the mutations were observed more frequently in patients than in controls. Patients with the mutations showed higher levels of serum IgA and higher in vitro IgA synthesis. In the luciferase assay, the regulatory gene with the mutations showed a potent effect for induction of the Iα1 germ-line transcript. The polymorphism in the Iα1 regulatory region possibly causes enhanced IgA production in some patients with IgAN.