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Objective@#To evaluate the association of smoking with the risk of ankylosing spondylitis (AS) using a Mendelian randomization (MR) approach.@*Methods@#A total of 16 383 186 AS-associated single nucleotide polymorphisms (SNPs), 378 smoking initiation associated SNPs and 126 lifetime smoking score-associated SNPs were collected from three large-scale genome-wide association studies (GWAS). The association of smoking phenotypes with the risk of AS was examined using inverse-variance weighted (IVW) with AS as a outcome variable, smoking initiation and lifetime smoking score as exposure factors and SNPs with strong associations with smoking as instrumental variables, and sensitivity analyses were performed with maximum likelihood-based method, MR pleiotropy residual sum and outlier (MR-PRESSO) test and MR-Egger regression analysis.@*Results@# A 33.5% increased risk of AS was found among genetically predicted smokers relative to non-smokers (OR=1.335, 95%CI: 1.059-1.682), and an increase in predicted lifetime smoking by per standard deviation resulted in a 101.4% increased risk of AS (OR=2.014, 95%CI: 1.341-3.024). The maximum likelihood-based method and MR-PRESSO test showed consistent correlated effect estimations and MR-Egger regression analysis identified no evidence of pleiotropy.@*Conclusion@#It is genetically predicted that smoking is associated with an increased risk of AS.
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Objective To evaluate the clinical value of recombinant major surface glycoprotein C(Msg C)consensus antigen of Pneumocystis jirovecii in serological diagnosis of Pneumocystis pneumonia(PCP), and explore serological diagnosis for PCP. Methods ELISA method was established for testing IgM antibody of Pneumocystis jirovecii Msg C consensus antigen. Serum antiMsg C consensus antigen IgM antibody and(1, 3)-β-D glucan were determined in 48 patients at high risk of PCP and 51 healthy subjects. The results of ELISA and(1, 3)-β-D glucan assay were compared with the results of PCR in bronchoalveolar lavage fluid. Results In a total of 99 specimens, Msg C consensus antigen IgM antibody detection(28.3％, 28/99)showed similar positive rate as(1, 3)-β-D glucan assay(25.3％, 25/99)(P>0.05). For the 48 patients at high risk of PCP, the positive rate of Msg C consensus antigen IgM antibody and(1, 3)-β-D glucan assay was 35.4％(17/48)and 33.3％(16/48), respectively(P>0.05). The two methods showed 67.7％ agreement in testing 99 specimens and 52.1％ agreement in testing 48 high-risk specimens. The bronchial lavage fluid samples of 48 patients at high risk were also tested by PCR. The result was positive in 15 cases(31.3％), showing no significant difference from Msg C consensus antigen IgM antibody test(P=0.665). The agreement between Msg C consensus antigen IgM antibody test and PCR was 58.3％. The agreement with PCR result increased to 84.0％ in the 25 specimens with the same result by two serological methods.When taking the positive result of either serological method as reference, serological method can detect majority of the PCR positive cases(86.7％, 13/15). Conclusions IgM antibody against Msg C consensus antigen in combination with serological marker(1, 3)-β-D glucan is valuable for PCP diagnosis. Further examination such as lower respiratory tract specimen PCR and conventional cytology should be carried out to confirm the diagnosis when both IgM antibody against Msg C consensus antigen and(1, 3)-β-D glucan are positive.