Objective. Neovascularization, with an increased number of synovial vessels with a characteristic morphology, seems to contribute to the progression of psoriatic arthritis (PsA). Accordingly, angiogenesis may be an important therapeutic target in PsA. The aim of this study was to analyze the effects of infliximab on angiogenesis in the synovial membrane of patients with PsA who responded to this therapy.Methods. The study group comprised 9 patients with PsA who were selected for the presence of active polyarthritis (including knee synovitis) despite methotrexate therapy. Clinical and biologic evaluations were performed at each visit. Arthroscopy and synovial biopsies were performed at week 0, before infliximab therapy was initiated, and at week 8, after administration of 3 intravenous infusions of infliximab (5 mg/kg). We used immunohistochemistry to identify changes in infiltrating cells and in the angiogenesis modulators ␣v␤3 integrin, vascular endothelial growth factor (VEGF), angiopoietin 2 (Ang-2), flt-1 (VEGF receptor 1 [VEGFR-1]), kinase insert domain receptor [KDR]/flk-1 (VEGFR-2), and stromal cell-derived factor 1 (SDF-1). Neovascularization was assessed by automated histomorphometry of CD31؉ vessels and by measuring ␣v␤3 expression.Results. Rapid and significant clinical and biological improvement were observed after treatment in all patients. In the synovium, infliximab therapy induced a significant reduction in macrophages, the CD31؉ vascular area, ␣v␤3؉ neovessels/Ulex europaeus agglutinin؉ vessels, VEGF and its receptor KDR/flk-1 (VEGFR-2), and SDF-1؉ vessels. Expression of flt-1 (VEGFR-1), and SDF-1 in lining cells showed a nonsignificant reduction, whereas expression of Ang-2 increased. In 3 patients, reverse transcription-polymerase chain reaction confirmed the changes in some of these markers at the messenger RNA level.Conclusion. These results show consistent changes in several factors involved in angiogenesis regulation, in parallel with the clinical response to infliximab in patients with PsA. The pattern of reduced VEGF with increased Ang-2 suggests vascular regression as a potential mechanism underlying the antiangiogenic effect of infliximab.

The sacroiliac joints are involved in most cases of axial spondyloarthropathy, the first manifestation usually being sacroiliitis. A finding of sacroiliitis at radiography is the classic diagnostic hallmark of axial spondyloarthropathy. However, radiographic changes reflect structural damage rather than active inflammation, which may delay the diagnosis by several years. In the past decade, the field of spondyloarthropathy has undergone major changes, largely driven by the development of new drugs for the treatment of ankylosing spondylitis. In recent years, the Assessment of SpondyloArthritis international Society has focused on the reassessment of existing classification criteria and the development and validation of diagnostic tools to facilitate early diagnosis and assessment of treatment response. Magnetic resonance (MR) imaging is the most recent innovation and the important change with respect to the previously established classification criteria. This modality has become an integral part of managing patients with sacroiliitis. MR imaging can serve as a biomarker of disease activity, allows monitoring, and can provide guidance for the treatment of affected patients, and it will likely become even more central to the care of these patients. Familiarity with the anatomy, anatomic variants, and physiologic changes of the sacroiliac joints is important for correctly interpreting findings and avoiding misdiagnosis.

The present findings establish the PDE3A-SLCO1C1 locus as a strong genetic marker of anti-TNF therapy response.

Background Tumour necrosis factor antagonists (anti-TNF-a) have demonstrated the efficacy in different chronic

ObjectiveAnti-TNF therapies have been highly efficacious in the management of rheumatoid arthritis (RA), but 25–30% of patients do not show a significant clinical response. There is increasing evidence that genetic variation at the Fc receptor FCGR2A is associated with the response to anti-TNF therapy. We aimed to validate this genetic association in a patient cohort from the Spanish population, and also to identify new genes functionally related to FCGR2A that are also associated with anti-TNF response.MethodsA total of 348 RA patients treated with an anti-TNF therapy were included and genotyped for FCGR2A polymorphism rs1081274. Response to therapy was determined at 12 weeks, and was tested for association globally and independently for each anti-TNF drug (infliximab, etanercept and adalimumab). Using gene expression profiles from macrophages obtained from synovial fluid of RA patients, we searched for genes highly correlated with FCGR2A expression. Tag SNPs were selected from each candidate gene and tested for association with the response to therapy.ResultsWe found a significant association between FCGR2A and the response to adalimumab (P=0.022). Analyzing the subset of anti-CCP positive RA patients (78%), we also found a significant association between FCGR2A and the response to infliximab (P=0.035). DHX32 and RGS12 were the most consistently correlated genes with FCGR2A expression in RA synovial fluid macrophages (P<0.001). We found a significant association between the genetic variation at DHX32 (rs12356233, corrected P=0.019) and a nominally significant association between RGS12 and the response to adalimumab (rs4690093, uncorrected P=0.040). In the anti-CCP positive group of patients, we also found a nominally significant association between RGS12 and the response to infliximab (rs2857859, uncorrected P=0.042).ConclusionsIn the present study we have validated the FCGR2A association in an independent population, and we have identified new genes associated with the response to anti-TNF therapy in RA.