To identify susceptibility loci for ankylosing spondylitis, we performed a two-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 1,356,350 autosomal SNPs in 1,837 individuals with ankylosing spondylitis and 4,231 controls; in the validation stage, we analyzed 30 suggestive SNPs in an additional 2,100 affected individuals and 3,496 controls. We identified two new susceptibility loci between EDIL3 and HAPLN1 at 5q14.3 (rs4552569; P = 8.77 × 10(-10)) and within ANO6 at 12q12 (rs17095830; P = 1.63 × 10(-8)). We also confirmed previously reported associations in Europeans within the major histocompatibility complex (MHC) region (top SNP, rs13202464; P < 5 × 10(-324)) and at 2p15 (rs10865331; P = 1.98 × 10(-8)). We show that rs13202464 within the MHC region mainly represents the risk effect of HLA-B*27 variants (including HLA-B*2704, HLA-B*2705 and HLA-B*2715) in Chinese. The two newly discovered loci implicate genes related to bone formation and cartilage development, suggesting their potential involvement in the etiology of ankylosing spondylitis.
The new ASDAS is a highly effective measure in assessing disease activity and a great discriminatory measurement to assess the efficacy of TNF-α inhibitor in Chinese AS patients and uSpA patients.
Rheumatic heart disease is the most severe complication of rheumatic fever. Till date, very few successful animal models of rheumatic valvular disease have been reported. This study aimed at developing a suitable animal model of chronic rheumatic valvulitis for further investigation and prevention of rheumatic heart disease. Lewis rats were immunized with one administration of formalin-killed and sonicated group A streptococci together with Complete Freund's Adjuvant every 7 days for three cycles followed by group A streptococci alone till killing. Control rats were administered adjuvants and saline. Rats in group 1 were killed 12 weeks after the initial injection. Rats in group 2 and control group were killed 24 weeks after the initial injection. Results 62.5% (5/8) of rats in group 1 developed myocarditis and 50% (4/8) developed valvulitis. Histological examination of cardiac sections showed only cellular infiltrates. In contrast, 75% (6/8) of rats in group 2 developed rheumatic-like myocarditis and 62.5% (5/8) developed chronic valvulitis. Histological manifestations of the hearts in group 2 animals involved not only acute damage such as cellular infiltrates, Aschoff-like cells, verrucous vegetation, but also chronic lesions such as fibrosis, vascular neogenesis. None of the rats (0/8) in control group presented myocarditis or valvulitis. Lewis rat repeatedly immunized with formalin-killed GAS may be a suitable animal model of chronic rheumatic valvulitis. It may be useful for future investigation of the pathogenesis and possible preventive strategies of human rheumatic heart disease.
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