Article Text
Abstract
Background: The SmD183–119 peptide is a major target of the B cell response in patients with systemic lupus erythematosus (SLE).
Objective: To investigate the T cell response directed against this peptide, its disease specificity, and possible impact on SLE pathogenesis.
Methods: Peripheral blood mononuclear cells derived from 28 patients with SLE and 29 healthy and disease controls were stimulated by the SmD183–119 and the recombinant (r)SmD1 protein, and [3H]thymidine incorporation was measured. Patients with SLE were simultaneously tested for autoantibodies, disease activity, clinical symptoms, and medical treatments.
Results: T cell reactivity against the SmD183–119 peptide was detected in 11/28 (39%) patients with SLE and against the rSmD1 protein in 10/28 (36%) patients. In contrast, only 2/29 (7%) controls exhibited SmD1 reactivity. An analysis of proliferation kinetics showed that SmD1 reactive T cells are activated in vivo, as additionally confirmed by cytometric analysis. Addition of mammalian dsDNA to rSmD1 enhanced the rSmD1-specific T cell response. SmD183–119-specific T cell reactivity was significantly more common in patients with cardiac and pulmonary symptoms. No correlation between T and B cell responses and disease activity was seen.
Conclusion: SmD183–119 is a major T cell epitope of SmD1, commonly recognised by T cells from patients with SLE and much less commonly found by healthy or disease controls. This strong T cell reactivity as well as the high frequency and specificity of anti-SmD183–119 antibodies in SLE suggest a possible role in SLE pathogenesis, at least in a subset of patients.
- SmD1 peptides
- systemic lupus erythematosus
- T cell reactivity
- ANA, antinuclear antibodies
- AU, arbitrary units
- BSA, bovine serum albumin
- CFSE, carboxyfluorescein diacetate succinimidyl ester
- CG, cell growth medium
- ELISA, enzyme linked immunosorbent assay
- PBMC, peripheral blood mononuclear cells
- PBS, phosphate buffered saline
- PHA, phytohaemagglutinin
- RA, rheumatoid arthritis
- SI, stimulation index
- SLE, systemic lupus erythematosus
- SLEDAI, SLE Disease Activity Index
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- ANA, antinuclear antibodies
- AU, arbitrary units
- BSA, bovine serum albumin
- CFSE, carboxyfluorescein diacetate succinimidyl ester
- CG, cell growth medium
- ELISA, enzyme linked immunosorbent assay
- PBMC, peripheral blood mononuclear cells
- PBS, phosphate buffered saline
- PHA, phytohaemagglutinin
- RA, rheumatoid arthritis
- SI, stimulation index
- SLE, systemic lupus erythematosus
- SLEDAI, SLE Disease Activity Index