Biomedical subjects

S Bayrak

Publications and source records attributed to S Bayrak.

4 recordsLinked to original sources

PubMed1998

Bystander suppression of murine collagen-induced arthritis by long-term nasal administration of a self type II collagen peptide.

Oral and more recently nasal tolerance have attracted attention as potential treatments of autoimmune disease. Arthritis induced by bovine type II collagen (CII) is a widely used animal model of rheumatoid arthritis, which is here used to investigate the efficacy of nasal treatment by a short peptide. The peptide spans residues 707-721 (designated p707), an epitope of mouse CII that is most strongly recognized after immunization of mice with this self-protein. The treatment was partially effective, but almost only when the peptide was administered in large doses over a prolonged period. Mice immunized with bovine CII respond mainly to other peptides, located in the CB11 fragment around amino acid residues 256-270. The tolerance effect therefore results from intramolecular suppression, between epitopes located in different parts of this large protein.

Administration, Intranasal↗

PubMed1997

T cell response of I-Aq mice to self type II collagen: meshing of the binding motif of the I-Aq molecule with repetitive sequences results in autoreactivity to multiple epitopes.

Type II collagen (CII) is of immunological interest because of its repetitive structure and properties as an autoantigen. The mouse gene has recently been cloned, thus enabling T cell-defined epitopes to be identified. Multiple novel epitopes on mouse CII are here detected in the autoreactive T cell response. The major response is directed to an epitope with residues 707-721 located on the CB10 fragment. Some 25 other epitopes are also recognized, including the autologous homologue of the 256-270 epitope which dominates in the response to foreign collagen. The cells reactive with mouse collagen peptides were of Th1 type, as judged by release of IFN-gamma. No significant reactivity was detected to mouse CII peptides during ongoing disease. Alignment of the mouse epitopes revealed a sequence motif with characteristic side chains at residues P1, P4 and P7, and to a lesser extent at P5, within a nonamer core sequence. Binding of these epitopes was simulated in a computer model of the I-Aq molecule, where peptides with anchor residues at P1, P4 and P7 were indeed found to fit the binding groove best. The spacing of pockets and the fine structure of the binding surface of the I-Aq molecule meshes with the repetitive structure of the collagen (X-Y-Gly), thus providing a likely explanation for the occurrence of multiple epitopes. Comparison with human DR binding motifs showed that the I-Aq motif resembles most closely that of the DR4 subtypes which predispose for rheumatoid arthritis.

Amino Acid Sequence↗

PubMed1996

Protective major histocompatibility complex genes and the role of interleukin-4 in collagen-induced arthritis.

To investigate the role of interleukin (IL)-4 during the triggering of collagen-induced arthritis, we examined the effects of the I-A(b) and I-E protective/suppressive genes and passively administered anti-IL-4 monoclonal antibody. In contrast to the action of I-E expression on its own, which has mainly a suppressive effect post-triggering, the combination of I-A(b) and I-E had a marked protective effect. Assuming, on the basis of previous experience with the I-A(b) allele, that it might act through suppressing early IL-4 production, we treated mice with the 11B11 IL-4-neutralizing antibody around the time of initial immunization with collagen. Treatment over a period extending to 6 days post-immunization exacerbated the arthritis, but when curtailed to 2 days post-immunization (and tested in pristane-primed animals), the disease was reduced. We conclude that IL-4 plays an essential role in triggering the disease.

Animals↗

PubMed1989

A practical test and its value in rheumatoid arthritis.

A practical test distinguishing some pathological conditions from the healthy state is described and a preliminary study on the value of this test for determining the disease activity in rheumatoid arthritis (RA) is presented. In this disease, the test was found positive in 97% of the cases, while rheumatoid factor (RF) was present in 57%, C reactive protein (CRP) in 83%, and elevated erythrocyte sedimentation rate (ESR) in 93% cases. When the activity of the disease disappeared, the test became negative. This test may be useful in RA for determining the active phase and evaluating treatment.

Arthritis, Rheumatoid↗