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Volume 3 Supplement 2

21st European Workshop for Rheumatology Research

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Characterization of RA33 (hnRNP-A2/B1)-autoreactive T cells in SLE-patients

SLE is a systemic autoimmune disease with distinct immunological characteristics including defective T cell functions, especially concerning IL2 production and proliferation. Furthermore, B-cell hyperactivity is observed leading to the formation of several characteristic autoantibodies (ab), among them ab to the heterogenous nuclear ribonucleoprotein A2/B1 (hnRNP/RA33). These antibodies are known to occur in over 20% of SLE patients.

In order to elucidate the role of T cells and their influence in antibody production in SLE, we studied proliferation of PBMC to purified hnRNP-A2/B1 in 34 SLE patients and 21 healthy controls.

While the stimulation indices (SI) in the healthy control group ranged from 0.5 to 3.5 (mean SI: 1.5 ± 0.9), the proliferative response of PBMC of the patient group ranged from 0.7 to 17 with a mean SI of 4.8 ± 4.0 (only 6 of 34 patients had an SI<2; P < 0.00004).

We then proceeded to draw RA33-specific T cell clones (TCC) by cultivation and limiting-dilution cloning of T cell lines. The generated 30 TCC derived from SLE patients and 19 TCC from healthy controls did not reveal a significant difference in SI and produced either more IFNγ than IL4 or none of these cytokines at all, suggesting that these TCC were of T1 or T0, but not T2 phenotype. Interestingly though, while only 11% of healthy control patients showed a CD4-/CD8+ subtype and 16% displayed a CD4+/CD8+ phenotype, 37% of TCC derived from SLE patients were CD4-/CD8+ (and 20 % expressed CD4 as well as CD8).

Our data reveal that more than 80 % of SLE-patients have a significant T cell reactivity (SI ≥ 2) to the nuclear protein hnRNP-A2/B1 indicating that the antibody response might be T cell driven. Furthermore, almost 60% of TCC derived from SLE patients were CD8+, which supports the importance of these T cells in SLE. Further studies will have to elucidate the pathogenetic implications of these findings.

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Fritsch, R., Eselböck, D., Jahn-Schmid, B. et al. Characterization of RA33 (hnRNP-A2/B1)-autoreactive T cells in SLE-patients. Arthritis Res Ther 3 (Suppl 2), P059 (2001).

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