Objective. To investigate mechanisms involved in inflammation and new bone formation in the sacroiliac (SI) joints of patients with ankylosing spondylitis (AS).Patients and methods. Computed tomographyassisted biopsy of the SI joint was performed in 5 patients with AS with a mean disease duration of 4.5 years and radiographic stage 2-3 disease. Immunohistologic studies were performed with the alkaline phosphatase-anti-alkaline phosphatase technique, and cytokine messenger RNA (mRNA) was detected by in si tu hybridization.Results. Dense cellular infiltrates with varying amounts of CD3+ cells (mean f SD 53.3 f 24.1%), CD4+ cells (29.7 f 17.6%), CDS+ cells (15.8 f 11.4%), CD14+ cells (23.6 f 16.9%), CD45RO+ cells (48.4 f 23.6%), and CD45RA+ cells (4.5 f 2.9%) were found in the synovial portion of the SI joints of all 5 patients. In these infiltrates a high amount of tumor necrosis factor a (TNFa) mRNA and, near the site of new bone formation, a lower amount of transforming growth factor / 3 (TGFP) mRNA, were detected, while no message for interleukin-1 was found in the 3 patients examined by this technique.Conclusion.

A major immunoregulatory mechanism in inflammatory infections and allergic dies Is the control of the balance of cytokines secreted by Thl/Th2 subsets of T helper (Th) cells. This might also be true in autoimmune diseas; a Th2 pattern that prevents an effective immune response in infections with intracellular bacteria may favor immunosuppression in autoimmune disease. The pattern of cytokine expression was compared in the synovial tissue from patients with a typical autoimmune disease, rheumatoid arthritis, and with a disorder with similar synovial pathology but driven by persisting exogenous antigen, reactive arthritis. We screened 12 rheumatoid and 9 reactive arthritis synovial tissues by PCR and in situ hybridization for their expression of T-cell cytokines. The cytokine pattern differs significantly between the two diseases; rheumatoid arthritis samples express a Thllike pattern whereas in reactive arthritis interferon y expression is accompanied by that of interleukin 4. Studying the expression of cytokines by in situ hybridization confimed the results found by PCR; they also show an extremely low frequency of cytokine-transcribing cells. In a double-staining experiment, it was demonstrated that interleukin 4 is made by CD4 cells. These experiments favor the possibility of therapeutic intervention in inflammatory rheumatic diseases by means of inhibitory cytokines.The control of the balance of cytokines secreted by differing T-cell subsets is emerging as a major immunoregulatory mechanism (1, 2). The division ofT helper (Th) cells into Thl [secreting interferon y (IFN-y) and interleukin (IL) 2] and Th2 (secreting IL-4 and IL-5) found in the mouse (3) holds good for humans (2), provided that attention is focused on IL-4 (4). Cytokines of the Thl spectrum are generally elevated in successful responses to a variety of intracellular pathogens (5), and Th2 cytokines are elevated in allergic diseases and in helminth infections (6, 7). The balance appears to be maintained not only by the cytokines considered originally to be of Thl/Th2 type but also by other inhibitory cytokines such as transforming growth factor (3 and I1-10, which are not confined to one ofthe original subsets and can additionally be secreted by non-T cells (8,9). In this context the pattern of T-cell cytokines in reactive and rheumatoid arthritis is of particular interest. Not only is rheumatoid arthritis among the commonest of the candidate autoimmune diseases, it also offers easy access to the site of inflammation. Reactive and rheumatoid arthritis are sister diseases, in the sense that both are characterized by inflammation of joints and the development of similar synovial pathology. Reactive arthritis is triggered by intracellular bacteria that persist in the joint (10,11), whereas for rheumatoid arthritis, the triggering events are unknown but thought not to involve persistent infection. Comparison ofthe two diseases should be informative.The importance of T cells in initiating and maintaining inflammation in the rheumatic diseases...

BackgroundInhibition of interleukin (IL)-1 represents a promising treatment option in adult-onset Still's disease (AOSD).ObjectiveTo investigate the efficacy and safety of canakinumab in patients with AOSD and active joint involvement by means of a multicentre, double-blind, randomised, placebo-controlled trial.MethodsPatients with AOSD and active joint involvement (tender and swollen joint counts of ≥4 each) were treated with canakinumab (4 mg/kg, maximum 300 mg subcutaneous every 4 weeks) or placebo. The primary endpoint was the proportion of patients with a clinically relevant reduction in disease activity at week 12 as determined by the change in disease activity score (ΔDAS28>1.2).ResultsAt enrolment, patients had high active disease with a mean DAS28(ESR) of 5.4 in the canakinumab and 5.3 in the placebo group, respectively. In the intention-to-treat analysis, 12 patients (67%) in the canakinumab group and 7 patients (41%) in the placebo group fulfilled the primary outcome criterion (p=0.18). In the per-protocol analysis, significantly higher American College of Rheumatology (ACR) 30% (61% vs 20%, p=0.033), ACR 50% (50% vs 6.7%, p=0.009) and ACR 70% (28% vs 0%, p=0.049) response rates were observed in the canakinumab group compared with the placebo group. Two patients in the canakinumab group experienced a serious adverse event.ConclusionAlthough the study was terminated prematurely and the primary endpoint was not achieved, treatment with canakinumab led to an improvement of several outcome measures in AOSD. The overall safety findings were consistent with the known profile of canakinumab. Thus, our data support indication for IL-1 inhibition with canakinumab in AOSD.

Sonography of the carotid and subclavian arteries aids in the detection of early Takayasu arteritis. In young females with unclear symptoms and laboratory findings of generalized inflammation, the primary extracranial branches of the aortic arch should be investigated by sonography to detect early Takayasu arteritis.

The first data from the JuMBO register indicate an improved long-term outcome of patients with severe JIA treated in the biologic era and an acceptable safety profile of ETA.