PMID- 16514412 OWN - NLM STAT- MEDLINE DCOM- 20060801 LR - 20111117 IS - 0022-202X (Print) IS - 0022-202X (Linking) VI - 126 IP - 7 DP - 2006 Jul TI - Role of IL-12B promoter polymorphism in Adamantiades-Behcet's disease susceptibility: An involvement of Th1 immunoreactivity against Streptococcus Sanguinis antigen. PG - 1534-40 AB - Adamantiades-Behcet's disease (ABD) is a chronic inflammatory multisystem disorder. Although the precise etiology is unclear, high prevalence of human leukocyte antigen (HLA)-B51 predisposition and predominantly involved T-helper type 1 cells (Th1)-type proinflammatory cytokines and extrinsic Streptococcal infection suggest a substantial association with an immunogenetic basis and strengthens the hypothesis that IL-12, a potent inducer of Th-1 immune reaction, is a putative candidate in its pathogenesis. These clinicopathological findings led us to examine interleukin 12 p40 (IL-12B) promoter polymorphism, for which the 4-base pair (bp) heterozygous insertion has been shown to affect the gene transcription and subsequent protein production. We analyzed IL-12B promoter genotypes in 194 Japanese subjects (92 with ABD and 102 normal controls) by PCR-based restriction enzyme digestion. The frequency of the insertion heterozygosity was significantly higher in patients than in controls (49/92, 53.3% vs 39/102, 38.2%, respectively). Comparing these with HLA haplotype data, this trend was more significant in HLA-B51-negative patients (29/42, 69.0% vs 20/50, 40.0%; P = 0.005). As assessed by semiquantitative reverse transcription-PCR and ELISA, stimulation with Streptococcal antigens specifically increased expression of IL-12 p40 mRNA and protein, in conjunction with IL-12 p70 induction, in peripheral blood mononuclear cells from heterozygous patients. Our results provide evidence for anti-bacterial host response toward Th1-immunity mediated by IL-12 in patients with ABD, and the possible insight into the genetic susceptibility that is independent of HLA background. FAU - Yanagihori, Hirokatsu AU - Yanagihori H AD - Department of Dermatology, Fukushima Medical University Graduate School of Medicine, Fukushima, Japan. yanagi@fmu.ac.jp FAU - Oyama, Noritaka AU - Oyama N FAU - Nakamura, Koichiro AU - Nakamura K FAU - Mizuki, Nobuhisa AU - Mizuki N FAU - Oguma, Keiji AU - Oguma K FAU - Kaneko, Fumio AU - Kaneko F LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060302 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (Antigens, Bacterial) RN - 0 (HLA-B Antigens) RN - 0 (HLA-B51 Antigen) RN - 0 (Interleukin-12 Subunit p40) RN - 0 (Protein Subunits) RN - 0 (RNA, Messenger) RN - 187348-17-0 (Interleukin-12) SB - IM CIN - J Invest Dermatol. 2006 Jul;126(7):1444-7. PMID: 16778812 MH - Adult MH - Aged MH - Antigens, Bacterial/*immunology MH - Behcet Syndrome/*genetics/immunology/physiopathology MH - Case-Control Studies MH - Cells, Cultured MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Expression Regulation MH - Genetic Predisposition to Disease/*genetics MH - HLA-B Antigens/genetics/immunology MH - HLA-B51 Antigen MH - Heterozygote MH - Humans MH - Interleukin-12/*genetics/physiology MH - Interleukin-12 Subunit p40 MH - Leukocytes, Mononuclear MH - Male MH - Middle Aged MH - *Polymorphism, Genetic MH - Promoter Regions, Genetic/*genetics MH - Protein Subunits/*genetics/physiology MH - RNA, Messenger/analysis/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Streptococcal Infections/immunology/physiopathology MH - Streptococcus sanguis/*immunology MH - Th1 Cells/*immunology EDAT- 2006/03/04 09:00 MHDA- 2006/08/02 09:00 CRDT- 2006/03/04 09:00 PHST- 2006/03/04 09:00 [pubmed] PHST- 2006/08/02 09:00 [medline] PHST- 2006/03/04 09:00 [entrez] AID - S0022-202X(15)32989-4 [pii] AID - 10.1038/sj.jid.5700203 [doi] PST - ppublish SO - J Invest Dermatol. 2006 Jul;126(7):1534-40. doi: 10.1038/sj.jid.5700203. Epub 2006 Mar 2.