Objective. To use a candidate gene approach for the identification of genetic markers that are significantly linked to and associated with ankylosing spondylitis (AS).Methods. We searched for novel polymorphisms in the ANKH gene (human homolog of the murine progressive ankylosis gene) and genotyped 2 polymorphic sites, one in the 5-noncoding region and the other in the promoter region of ANKH, using DNA from affected (n ‫؍‬ 273) and unaffected (n ‫؍‬ 112) individuals from 124 AS families. We used these ANKH and other nearby polymorphisms to perform linkage and family-based association analyses.Results. We identified 2 novel polymorphic sites: one in the 5-noncoding region of ANKH involving 1-2 copies of an 8-bp repeat (denoted as ANKH-OR), and the other in the promoter region involving different copy numbers of a triplet repeat (denoted as ANKH-TR). ANKH-OR and ANKH-TR were in complete linkage disequilibrium. Five markers (D5S1953, ANKH-TR, ANKH-OR, D5S1954, and D5S1963) were used for both the linkage and association analyses. Multipoint linkage analysis of 124 AS families showed a modest level of significance (nonparametric linkage score 2.15; P ‫؍‬ 0.015) at the ANKH region. The contribution of ANKH to AS susceptibility ( s ) was 1.9. A family-based association study on the same AS families revealed that both ANKH-OR allele 1 and ANKH-TR allele 7 were significantly associated with disease, assuming an additive model (for ANKH-OR allele 1, P ‫؍‬ 0.03; for ANKH-TR allele 7, P ‫؍‬ 0.04).Conclusion. Our results indicate that ANKH-OR and ANKH-TR are novel genetic markers that are significantly associated with AS.

Our analysis of affected and unaffected family members in familial AS demonstrated no significant differences with respect to cellular or humoral immune responses to K. pneumoniae and three control microbes. In addition, K. pneumoniae did not exhibit a predominant immune response in affected individuals. Thus we find no supportive evidence to implicate a causal role for K. pneumoniae in familial AS.

Objective. Ankylosing spondylitis (AS) is a progressive disease in which chronic inflammation can lead to extensive new bone formation throughout the spine. At present, few measures of the activity or extent of the disease are available. In this study, we sought to determine whether markers of cartilage synthesis and degradation could provide such quantitative measures.Methods. Serum samples from 23 patients receiving infliximab treatment for AS were obtained at baseline and at weeks 2, 6, 14, and 22. Conclusion. In AS, elevated serum levels of CPII and the 846 epitope may be related to biosynthetic turnover of hyaline cartilage and the intervertebral discs but may also reflect progressive bone formation as a result of endochondral ossification. The correlation of the CPII:C2C ratio with CRP suggests that the CPII: C2C ratio might prove to be a useful marker of disease activity in AS.The hallmark of ankylosing spondylitis (AS) is acute and chronic inflammation in the sacroiliac joints as well as enthesitis, defined as inflammation at the sites of ligamentous and tendinous insertions onto bone. To a varying degree, peripheral joint synovitis can also be a prominent feature. Previously, pathologic studies revealed the presence of T cells and macrophages and local expression of tumor necrosis factor ␣ (TNF␣) in biopsy specimens from the sacroiliac joints of patients with active AS (1).

Tumor necrosis factor (TNF) has generally been regarded as a protective cytokine in host defense against bacterial infections. In the present study, we evaluated the role of TNF in the acute phase of infection by Yersinia enterocolitica by using mice rendered genetically deficient in TNF receptor p55 (TNFRp55؊/؊ mice showed more effective resistance to the bacteria, reflected in enhanced bacterial clearance and less tissue damage, than did control C57BL/6 mice. C57BL/6 mice showed evidence of extensive apoptosis in the spleen accompanied by a selective decrease in the CD4 ؉ -T-cell population of splenocytes, whereas TNFRp55 ؊/؊ mice were spared these changes. The splenocytes from TNFRp55 ؊/؊ mice also maintained a robust gamma interferon IFN-␥ response to mitogenic stimulation, while the comparable response in C57BL/6 mice was impaired. In addition, splenocytes harvested from infected mice demonstrated lower production of interleukin-10 IL-10 in TNFRp55؊/؊ mice than in C57BL/6 mice. These findings suggest that Yersinia can induce TNFRp55-mediated apoptosis of splenocytes in the acute phase of the infection and that alteration of T-cell-generated cytokines can dramatically alter the early events in host defense against this pathogen.