Objective
The Sa autoantigen can be found in inflamed synovium of patients with rheumatoid arthritis (RA), and at least part of the humoral RA‐specific anti‐Sa response is directed against ...citrullinated vimentin. This study was undertaken to evaluate the sensitivity, specificity, and prognostic value of determination of levels of antibodies against modified citrullinated vimentin (anti‐MCV) as compared with antibodies against cyclic citrullinated peptides (anti‐CCP) in an inception cohort of patients with early RA.
Methods
Clinical data, radiographs, and measurements of levels of anti‐MCV and anti‐CCP antibodies were obtained in 273 patients with early RA at baseline, after 3 months, and after 1, 2, 3, and 5 years. Autoantibodies were also analyzed in 100 healthy controls.
Results
Of the 273 patients, 193 (70.7%) were anti‐MCV positive and 158 (57.9%) were anti‐CCP positive at the time of diagnosis, with nearly equal specificities (95% and 96%, respectively). Forty (14.7%) were anti‐MCV positive only, and 5 (1.8%) were anti‐CCP positive only. Anti‐MCV–positive and anti‐MCV–negative patients had similar disease activity at baseline, but presence of anti‐MCV was predictive of subsequent high disease activity and continued radiographic progression. Changes in anti‐MCV level showed stronger correlation with changes in clinical parameters than did changes in anti‐CCP level. The subgroup of patients who were anti‐MCV positive and anti‐CCP negative showed a higher rate of radiographic destruction than did patients who were negative for both anti‐MCV and anti‐CCP.
Conclusion
These findings show that when patients with early RA are compared with healthy controls, analysis of anti‐MCV yields greater sensitivity and unchanged specificity as compared with analysis of anti‐CCP. Anti‐MCV also appears to perform better than anti‐CCP in identifying poor radiographic prognosis in patients with early RA.
Abstract
In the homeostasis of the immune system regulatory cells play a major role. Removal of one group of regulatory cells, the CD25
+
CD4
+
T cells, leads to autoimmune manifestations in ...experimental animal models, and reintroduction of this population prevents disease. This study addresses the role of such regulatory T cells in humans with an autoimmune disease, where we demonstrate the presence of CD25
bright
CD4
+
T cells in the target organ of patients with active rheumatoid arthritis. The patients displayed an enrichment of CD25
bright
CD4
+
T cells in synovial fluid as compared to peripheral blood. These cells are functional regulatory cells, as they were able to suppress
in vitro
proliferation of autologous T cells, bothfrom synovial and peripheral blood origin. Although the frequency of CD25
bright
CD4
+
T cells varied between patients, it was found to be constant over time in any one joint during each relapse. Numbers were also comparable in two inflamed knee joints of one and the same patient, emphasizing the symmetry of the disease. In summary, it is striking that in addition to all activated, potentially pathological T cells the synovial fluid from RA patients also contains CD25‐expressing CD4
+
T cells with a regulatory capacity.
Objective
Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated ...with biologics is scarce and of uncertain generalizability to low‐risk populations, this study sought to determine the risk of TB among Swedish patients with RA.
Methods
Using data from Swedish nationwide and population‐based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.
Results
During 1999–2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval 95% CI 1.2–3.4). RA patients treated with TNF antagonists had a 4‐fold increased risk of TB (relative risk 4.0, 95% CI 1.3–12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999–2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.
Conclusion
Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999–2001, TNF antagonists were associated with an increased risk of TB, up to 4‐fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
CD25+CD4+ regulatory T cells participate in the regulation of immune responses. We recently demonstrated the presence of CD25brightCD4+ regulatory T cells with a capacity to control T cell ...proliferation in the joints of patients with rheumatoid arthritis. Here, we investigate a possible accumulation of these regulatory T cells in the inflamed joint of different rheumatic diseases including rheumatoid arthritis. The studies are also extended to analyze whether cytokine production can be suppressed by the regulatory T cells. Synovial fluid and peripheral blood samples were obtained during relapse from 36 patients with spondyloarthropathies, 21 adults with juvenile idiopathic arthritis and 135 patients with rheumatoid arthritis, and the frequency of CD25brightCD4+ T cells was determined. Of 192 patients, 182 demonstrated a higher frequency of CD25brightCD4+ T cells in synovial fluid than in peripheral blood. In comparison with healthy subjects, the patients had significantly fewer CD25brightCD4+ T cells in peripheral blood. For functional studies, synovial fluid cells from eight patients were sorted by flow cytometry, and the suppressive capacity of the CD25brightCD4+ T cells was determined in in vitro cocultures. The CD25brightCD4+ T cells suppressed the production of both type 1 and 2 cytokines including interleukin-17, as well as proliferation, independently of diagnosis. Thus, irrespective of the inflammatory joint disease investigated, CD25brightCD4+ T cells were reduced in peripheral blood and enriched in the joint, suggesting an active recruitment of regulatory T cells to the affected joint. Their capacity to suppress both proliferation and cytokine secretion might contribute to a dampening of local inflammatory processes.
BACKGROUND:An association between Down syndrome and celiac disease has been reported. This study was conducted to determine the association between childhood celiac disease and Down syndrome in the ...county of Uppsala, Sweden.
METHODS:All 76 children with Down syndrome (1-18 years) were screened for the occurrence of anti-gliadin antibodies (AGA) and anti-endomysium antibodies (EMA). Twelve children with suspected celiac disease were investigated further.
RESULTS:Increased levels of both IgA and IgG AGA were found in 26% of the children and of EMA in and 5 of 76. Celiac disease was diagnosed in at least three of the children (3.9%; 95% confidence interval 0%-8.3%), and it could have been present in as many as eight. Three of the five EMA-positive children with suspected celiac disease had the HLA phenotype DR3, DQ2.
CONCLUSIONS:The results show that determination of EMA is more useful as a screening test for celiac disease and for follow-up than is AGA in children with Down syndrome. The present study also confirms that celiac disease is overrepresented among Swedish children with Down syndrome and that celiac disease should be considered in all persons with Down syndrome.
Antibodies directed against citrullinated proteins (anti-CP) constitute a newly defined group of autoantibodies with very high diagnostic specificity for rheumatoid arthritis (RA). The most recently ...developed assays have a sensitivity comparable to that of traditional tests for Rheumatoid Factor (RF). Due to its considerably higher specificity, the authors recommend that anti-CP antibody analysis should replace the RF test in primary healthcare when investigating cases of clinically suspect RA.
An intradermal injection of Freund's incomplete adjuvant oil (FIA) without further additives was shown to induce erosive polyarthritis in dark Agouti (DA) rats, but not in Lewis rats. Histological ...examination revealed joint inflammation, first with polymorphonuclear cells and synovial hyperplasia, and subsequently, with multinucleated giant cells. Both constituents of FIA, mineral oil and Arlacel A, as well as Pristane oil were arthritogenic, whereas vegetable oil were not. Re-administration of adjuvant oil after recovery failed to induce arthritis, thus making possible a role of specific immunity in this new form of arthritis in rats.