Absence of Persistent Microbial Antigen

As frequently occurs in suspected autoimmune diseases, there is no direct evidence of an autoimmune process. Cartilage has been proposed as the most likely target of any such response [76, 81]. It cannot be excluded that microbial antigens persist in the diverse structures involved, but this does not seem likely. Furthermore, biopsies from the sacroiliac joints have proved negative for candidate bacteria by PCR [14].

The cartilage-derived candidate autoantigens most investigated in animal models are collagen type II and proteoglycan, the major components of cartilage and other periarticular structures. While the collagen Il-induced arthritis model resembles RA, animals immunized with proteoglycan show features typical of AS [5,121]. The G1 globular domain of aggrecan, the major proteoglycan protein, has been identified as immunodominant in this model. The proteoglycan link protein has been suggested as another candidate. These proteins also occur in the eye and the aorta, and a T cell response against both has also been demonstrated in human arthritides, including AS, RA and juvenile chronic arthritis. We could also recently demonstrate a CD4+ [122] and a CD8+ [123] T cell response to aggrecan-derived peptides in the peripheral blood from AS patients, although this was not HLA-B27 restricted. We subsequently used computer prediction to screen all cartilage proteins for candidate peptides likely to stimulate HLA-B27-restricted CD8+ T cells [3]. From this we isolated approximately 120 nonameric peptides, which were then tested for in vitro stimulation of CD8+ T cells from patient synovial fluid. We identified one peptide from collagen type VI that was stimulatory in five out of seven patients. All these data are compatible with a cartilage-directed autoimmune response in the disease pathogenesis, but proof for this is still lacking and we shall investigate this question further.

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Arthritis Relief and Prevention

Arthritis Relief and Prevention

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