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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.
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 suggests 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. The 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. ) -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 / 102,3 8.2%, 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) 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.