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IMPORTANCE: Although experimental studies support the hypothesis that exposure of infectious agents may trigger an aberrant immune response and contribute to noninfectious uveitis, the association of a definite pathogen with human noninfectious uveitis conditions appears not to have been well established in a population. OBJECTIVE: To evaluate associations of tuberculosis infection with risk of several noninfectious uveitis conditions. DESIGN, SETTING, AND PARTICIPANTS: These mendelian randomization and observational analyses were conducted with the genetic data of a Chinese cohort enrolled between April 2008 and January 2018 and a Japanese cohort enrolled between January 2002 and June 2009. We recruited participants for T-SPOT.TB (Oxford Immunotec) assays between July and November 2019. The Chinese cohort included patients with uveitis associated with Behçet disease or other uveitis conditions and control participants. The Japanese cohort and the group given T-SPOT.TB assays included individuals with Behçet disease and control participants. Data analyses for this study were completed from July 2019 to January 2020. EXPOSURES: Genetic variants associated with tuberculosis as natural proxies for tuberculosis exposure. MAIN OUTCOMES AND MEASURES: The primary outcome was the odds ratio (OR) for Behçet disease, estimated by an inverse variance weighted mean of associations with genetically determined tuberculosis susceptibility. The T-SPOT.TB positivity rate was examined in individuals with Behçet disease and compared with that of control participants. RESULTS: The Chinese cohort included 999 patients with uveitis associated with Behçet disease, 1585 with other uveitis conditions, and 4417 control participants. The Japanese cohort included 611 individuals with Behçet disease and 737 control participants. The group given T-SPOT.TB assays included 116 individuals with Behçet disease and 121 control participants. Of the Chinese individuals with Behçet disease and control participants, 2257 (41.7%) were female and the mean (SD) age was 35.4 (12.5) years. In the Japanese cohort, 564 (41.8%) were female and the mean (SD) age was 39.1 (12.7) years. Genetically determined tuberculosis susceptibility was associated with an increased risk for Behçet disease. The OR for Behçet disease per 2-fold increase in tuberculosis incidence was 1.26 (95% CI, 1.12-1.43; P = 1.47 × 10−4). Replication using the Japanese cohort yielded similar results (OR, 1.16 [95% CI, 1.08-1.26]). In T-SPOT.TB assays, having a positive result, indicating a history of tuberculosis infection, was found to be an independent risk factor for Behçet disease (OR, 2.26 [95% CI, 1.11-4.60]). CONCLUSIONS AND RELEVANCE: These human genetic and biomarker data demonstrated that tuberculosis exposure was a risk factor for Behçet disease. This study provides novel evidence linking an infectious agent to the risk of a noninfectious uveitis condition.

We analyzed 1,900 Turkish Behçet's disease cases and 1,779 controls genotyped with the Immunochip. The most significantly associated SNP was rs1050502, a tag SNP for HLA-B*51. In the Turkish discovery set, we identified three new risk loci, IL1A–IL1B, IRF8, and CEBPB–PTPN1, with genome-wide significance (P < 5 × 10−8) by direct genotyping and ADO–EGR2 by imputation. We replicated the ADO–EGR2, IRF8, and CEBPB–PTPN1 loci by genotyping 969 Iranian cases and 826 controls. Imputed data in 608 Japanese cases and 737 controls further replicated ADO–EGR2 and IRF8, and meta-analysis additionally identified RIPK2 and LACC1. The disease-associated allele of rs4402765, the lead marker at IL1A–IL1B, was associated with both decreased IL-1α and increased IL-1β production. ABO non-secretor genotypes for two ancestry-specific FUT2 SNPs showed strong disease association (P = 5.89 × 10−15). Our findings extend the list of susceptibility genes shared with Crohn's disease and leprosy and implicate mucosal factors and the innate immune response to microbial exposure in Behçet's disease susceptibility.

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In the reactions of decaisopropylbicyclo[2.2.0]hexasilane (1) with hydrobromic acid and hydrochloric acid, the bridgehead Si–Si bond of 1was selectively cleaved to give 1-halo-1,2,2,3,3,4,5,5,6,6-decaisopropylcyclohexasilanes. The X-ray crystallographic analysis of the products indicates that the cis-addition of the acids to the Si–Si bond is preferable.

The photolysis of tricyclic ladder oligosilanes gave a cyclotetrasilene intermediate, which was trapped by methanol, 2,3-dimethyl-1,3-butadiene, and anthracene. Anthracene underwent a cycloaddition with the cyclotetrasilenes at the 9,10- and 1,4-positions depending on the substituents on the cyclotetrasilene rings.

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