Analysis of VH gene rearrangement and somatic hypermutation in Sjogren's syndrome and IgG4-related sclerosing sialadenitis.

Abstract

IgG4-related sclerosing sialadenitis is currently considered as an autoimmune disease distinct from Sjogren's syndrome (SS) and responds extremely well to steroid therapy. To further elucidate the characteristics of IgG4-related sclerosing sialadenitis, we analysed VH fragments of IgH genes and their somatic hypermutation in SS (n = 3) and IgG4-related sclerosing sialadenitis (n = 3), using sialolithiasis (n = 3) as a non-autoimmune control. DNA was extracted from the affected inflammatory lesions. After PCR amplification of rearranged IgH genes, at least 50 clones per case (more than 500 clones in total) were sequenced for VH fragments. Monoclonal IgH rearrangement was not detected in any cases examined. When compared with sialolithiasis, there was no VH family or VH fragment specific to SS or IgG4-related sclerosing sialadenitis. However, rates of unmutated VH fragments in SS (30%) and IgG4-related sclerosing sialadenitis (39%) were higher than that in sialolithiasis (14%) with statistical significance (P = 0.0005 and P < 0.0001, respectively). This finding suggests that some autoantibodies encoded by germline or less mutated VH genes may fail to be eliminated and could play a role in the development of SS and IgG4-related sclerosing sialadenitis.

• Authors: H Sakuma, F Okumura, S Miyabe, M Sugiura, T Joh, K Shimozato, H Inagaki
• Journal: Scandinavian journal of immunology (Scand J Immunol) Vol. 72 Issue 1 Pg. 44-9 (Jul 2010) ISSN: 1365-3083 [Electronic] England
• PMID: 20591075 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Immunoglobulin G
• Immunoglobulin Heavy Chains
• DNA

Topics

• Aged
• Biopsy
• Cloning, Molecular
• DNA (chemistry, genetics)
• Female
• Gene Rearrangement (genetics, immunology)
• Humans
• Immunoglobulin G (genetics, immunology)
• Immunoglobulin Heavy Chains (genetics, immunology)
• Immunohistochemistry
• Male
• Middle Aged
• Polymerase Chain Reaction
• Sialadenitis (genetics, immunology)
• Sjogren's Syndrome (genetics, immunology)
• Somatic Hypermutation, Immunoglobulin (genetics, immunology)