M M Souto-Carneiro

Alterations on peripheral blood B-cell subpopulations in very early arthritis patients

OBJECTIVE To characterize circulating B-cell subpopulations of arthritis patients with <6 weeks of disease duration. METHODS Peripheral blood samples were collected from very early untreated polyarthritis patients, with <6 weeks of disease duration, for flow cytometric evaluation of B-cell subpopulations. Samples from patients who were later diagnosed as RA [very early RA (VERA)] were also collected 4-6 weeks after starting a low dose of prednisone (5-10 mg) and 4 months after reaching the minimum effective dose of MTX. A matched healthy group was used as a control. RESULTS VERA patients have a lower percentage of total peripheral blood memory B cells (CD19(+)CD27(+)) and a significant decrease in the frequency of circulating pre-switch memory B cells (CD19(+)IgD(+)CD27(+)) as compared with controls. Therapy with corticosteroids or MTX was unable to restore the normal frequencies of these B-cell subpopulations. A significant decrease in peripheral pre-switch memory B cells is equally observed in other early arthritis patients. Furthermore, no significant differences are found in the frequencies of CD4(+) and CD8(+) T cells in all patient groups. CONCLUSIONS In very early polyarthritis patients, there is a reduction in circulating pre-switch memory B cells. The reasons that may account for this effect are still unknown. Short-term corticosteroids and MTX do not seem to have a direct effect on circulating B-cell subpopulations in VERA patients.

Cytokine pattern in very early rheumatoid arthritis favours B-cell activation and survival

OBJECTIVES B cells play an important role in the perpetuation of RA, particularly as autoantibody-producing cells. The ICs that further develop deposit in the joints and aggravate the inflammatory process. However, B-cell contribution in the very early stage of the disease remains unknown. The main goal of this work was to determine the concentration of cytokines potentially relevant for B-cell activation in serum from very early polyarthritis patients, with <6 weeks of disease duration, who latter on evolved into very early RA (VERA). METHODS A proliferation-inducing ligand (APRIL), B-cell activating factor (BAFF) and IL-21 levels were measured by ELISA in the serum of VERA, other very early arthritis (VEA), established RA patients and controls. SF samples of established RA were also analysed. RESULTS VERA patients have higher levels of APRIL and BAFF as compared with VEA, established RA and controls. Furthermore, APRIL and BAFF levels are also significantly elevated in RA-SF when compared with serum. CONCLUSIONS The increased levels of APRIL and BAFF in VERA patients suggests that B-cell activation and the development of autoreactive B-cell responses might be crucial in early phases of RA. Therefore, APRIL and BAFF could be promising targets for therapy in the early phase of RA.

Cytokine pattern in very early rheumatoid arthritis favours B cell activation and survival

B cells play an important role in the perpetuation of rheumatoid arthritis (RA), particularly as autoantibody producing cells. The immune complexes that further develop deposit in the joints and aggravate the inflammatory process. However, B cells contribution in the very early stage of the disease remains unknown.

Spondyloarthritis and rheumatoid arthritis: different clinical manifestations, similar cytokine network

Background The reasons for the phenotypic differences between spondyloarthritis (SpA) and rheumatoid arthritis (RA) are still unclear. Slight divergences in cytokine networks driving the pathologies might contribute to the distinct clinical manifestations and may represent new treatment opportunities. Objectives The main goal of this work was to compare serum and synovial cytokines in established SpA and RA patients. Materials and methods The concentration of a panel of cytokines was measured in the serum of SpA and RA patients, as well as in synovial fluid from SpA, RA and osteoarthritis patients. Results The authors found that SpA and RA patients shared a similar pattern of cytokine concentration, with the exception of higher levels of interleukin-21 in the synovial fluid of RA patients. Conclusions Our results suggest that although SpA and RA are chronic inflammatory diseases with clearly distinct clinical manifestations, both pathologies share a similar cytokine profile, including Th17-related cytokines.

Disease amelioration in the K/BxN mouse model of spontaneous chronic arthritis after CD8 T cell depletion

CD8 T cells are part of the T cell pool infiltrating the rheumatoid synovial membrane. Moreover, CD8 T cells have been linked to the formation of synovial ectopic germinal centres in rheumatoid arthritis (RA), and they produce proinflammatory cytokines. Hence, CD8 T cells appear to be intimately involved in initiating and maintaining the chronic inflammation in the RA synovium. Nevertheless, studies on animal models of …

Spondyloarthropathy and rheumatoid arthritis: two different diseases, a similar cytokine network

The reasons for the phenotypic differences between spondyloarthritis (SpA) and rheumatoid arthritis (RA) are still unclear. Slight divergences in the cytokine networks might contribute to this and may be the key to new treatment approaches.

Identification of a cytokine network sustaining neutrophil and Th17 activation in untreated early rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by sustained synovitis. Recently, several studies have proposed neutrophils and Th17 cells as key players in the onset and perpetuation of this disease.

Cytokine network in the first 6 weeks of rheumatoid arthritis onset

Rheumatoid arthritis (RA) is a chronic inflammatory disease mainly characterised by synovial hyperplasia and joint destruction. Although the aetiopathology of this autoimmune disease is not completely understood, it is known that it is associated with a misregulation of both the cellular immune system and the cytokine network. Nevertheless, little is known about the blood cytokine milieu in the first few weeks of RA. To determine …