engleski

The frequency of lymphocyte subpopulations and regulatory cells simultaneously on local and systemic levels of acute rheumatoid arthritis

Background: Rheumatoid arthritis (RA) is an inflammatory disease with autoimmune features affecting synovial joints. In severe cases there are extraarticular and systemic complications. The basic aetiology of the disease is not known, but aside for purely genetic predisposition, there is abundant evidence suggesting the possibility that lymphocytes might be central in the pathogenic mechanism of joint destruction and extraarticular complications in RA. The pathogenetic role of different lymphocyte sets and subsets has been investigated broadly in the peripheral blood (PB), the synovial fluid (SF), and the synovial membrane (SM) of RA patients, revealing significant oscillation in their levels. The question of which T cells contribute to the pathogenetic changes in the early phase of the disease, and which predominantly contribute to the perpetuation of synovial inflammation in RA, remain still unanswered. Objectives: The purpose of this study is to determine the frequency and distribution of lymphocyte subpopulations and regulatory cells simultaneously on local (synovial fluid and synovial membrane) and systemic levels (peripheral blood) of acute RA patients. Methods: Samples of peripheral venous blood, synovial fluid and synovial membrane were obtained from 25 patients with RA at the time of hip or knee replacement or at control examination, and from 10 OA patients as a control group. Mononuclear cell populations were separated and analysed by two-color flow cytometry. Results: 1.)The frequency of total T lymphocytes was similar on both local and systemic levels in the acute stage of RA. However, the percentages measured (70%) in our study were close to the upper range of values found in other investigations (30-70%). 2.) In spite of the fact that no difference was detected in the level of CD3+ cells, significant changes were found in the CD4+ subpopulation of CD3+ cells which, during the acute phase of RA, were the highest in synovial membrane, where the pathologic process occurs. 3.) Contrary to the results regarding the CD4+ T cell population, the frequency of CD8+ cytotoxic T lymphocytes - known to constitutively express perforin molecule in their cytoplasm - was higher in the synovial fluid of acute RA patients, compared to their frequency in peripheral blood and synovial membrane. 4.) These results were followed by changes in the CD4/CD8 ratio, which was decreased in SF, but increased in SM, compared to PB. 5) A preliminary immunophenotypic study in RA patients, has revealed a decreased frequency of the CD4+CD25bright cell population, known to be T regulatory cells, in synovial fluid compartment. 6) The percentage of CD3-CD56+ cells was not significantly different on local and systemic levels, but the significantly lower percentage of CD3-CD16+ cells in the synovial fluid implied the presence of a CD16-CD56+ NK cell subpopulation. Conclusion: A significantly different lymphocyte distribution was observed on local and systemic levels in the same group of acute RA patients. This observed specificity of local immune responses occurring in the synovial membrane and the synovial fluid suggests that lymphocytes play a crucial pathogenic role in the initial stages of rheumatoid arthritis, and confirms the hypothesis that imbalance between activated responder and regulatory T cells appears to influence the immunopathogenesis of RA.

RA pathogenesis; lymphocytes; T regulatory cells

nije evidentirano