engleski

The phenotypic characteristic of dendritics cells in diferent tissue compartments in rheumatoid arthritis patients

Rheumatoid arthritis (RA) is one of the most common immune-mediated inflammatory disease characterized by intra-articular inflammation and synovial hyperplasia that results in progressive degradation of cartilage and bone, and often with systemic complications. Despite a welth of advance in understanding of efferent mechanism of tissuae destruction in RA, the underlying pathogenesis of this disease is still unknown, and RA still represents a great challenge to clinical therapy and basic immunological science. In complicated interplay among lymphatic cell populations involved in RA, dendritic cells (DC) as a components of tne innate immune system could be important in initiating the immunopathology in RA. DCs are known as the most potent antigen presenting cells, but also have a regulatory role in tolerance induction. It is proposed that functional plasticity DCs for initiating tolerance or immunity depends either on a subtype of specialized regulatory DCs involved in the process or on the degree of DC maturation during which expression of CD83 marker and other adhesion and co-stimulatory molecules are changing. The aim of this study was to characterise the developmental orgin and also the maturational and activational state of DCs from freshly isolated tissuae compartments of acute and chronic RA patients and compare them to osteoarthritic (OA) patients. Samples of peripheral venous blood, synovial fluid and synovial membrane were obtained from 17 patients with RA at the time of hip replacement or at control examination, and from 8 OA patients as a control group. Mononuclear cell populations were separated and analysed by two-and three-color flow cytometry for the folowing receptors: CD45, CD3, CD4, CD8, CD56+CD16, HLA-DR, adhesion molecule CD11c and costimulatory receptors CD83 and CD86. Results: 1) A highly differentiated subpopulation of DCs in synovial tissue compartments that expressed an activated phenotype (CD83+, CD86+, HLA-DR+, CD11c+) are detected in higher percentage in RA patients comparing to OA patients that serve as a control. 2) A higher degree of CD83+DCs with activated (HLA-DR+) phenotype was observed in synovial membrane comparing to synovial fliud compartment in acute RA patients. This difference is not statistically significant in chronic phase of disease. 3) In synovial membrane and synovial fluid of RA patients, CD83+Dcs are predominantly of CD11c+highCD123(IL-3R)+low phenotype, suggesting their myeloid orgin. 4) Peripheral blood DCs of RA patients are predominantly of immature phenotype (CD83 negative) and among CD83+DCs there are nearly equal distribtion of CD11c+highCD123+low and CD11c+lowCD123+cells. 5) CD83+DC in all examined joint tissue compartments of acute RA patients express high frequency of HLA-DR and CD86. Immunophenotypical differences of mature (CD83+) DCs in various compartments of RA patients in different clinical stages suggest important role of these cells in initial pathogenetic events of the disease and could represent an attractive target for therapeutic intervention in future.

rheumatoid arthritis; dendritic cells

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