IntroductionRheumatoid 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. The main goal of this work was to determine whether cytokines driving neutrophil and Th17 activation are dysregulated in very early rheumatoid arthritis patients with less than 6 weeks of disease duration and before treatment (VERA).MethodsCytokines related to neutrophil and Th17 activation were quantified in the serum of VERA and established RA patients and compared with other very early arthritis (VEA) and healthy controls. Synovial fluid (SF) from RA and osteoarthritis (OA) patients was also analyzed.ResultsVERA patients had increased serum levels of cytokines promoting Th17 polarization (IL-1β and IL-6), as well as IL-8 and Th17-derived cytokines (IL-17A and IL-22) known to induce neutrophil-mediated inflammation. In established RA this pattern is more evident within the SF. Early treatment with methotrexate or corticosteroids led to clinical improvement but without an impact on the cytokine pattern.ConclusionsVERA patients already display increased levels of cytokines related with Th17 polarization and neutrophil recruitment and activation, a dysregulation also found in SF of established RA. 0 Thus, our data suggest that a cytokine-milieu favoring Th17 and neutrophil activity is an early event in RA pathogenesis.

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.

The objective of this study was to assess whether clinical measures of rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha (TNF-α) promoter genotype/haplotype markers. Each patient's disease activity was assessed by the disease activity score using 28 joint counts (DAS28) and functional capacity by the Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated by the Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, joint surgeries, and work disability were also assessed. The promoter region of the TNF-α gene, between nucleotides -1,318 and +49, was sequenced using an automated platform. Five hundred fifty-four patients were evaluated and genotyped for 10 single-nucleotide polymorphism (SNP) markers, but 5 of these markers were excluded due to failure to fall within HardyWeinberg equilibrium or to monomorphism. Patients with more than 10 years of disease duration (DD) presented significant associations between the -857 SNP and systemic manifestations, as well as joint surgeries. Associations were also found between the -308 SNP and work disability in patients with ACR = American College of Rheumatology; DAS28 = disease activity score using 28 joint counts; DD = disease duration; DMARD = disease-modifying anti-rheumatic drug; EM = expectation-maximization; ESR = erythrocyte sedimentation rate; HAQ = Health Assessment Questionnaire; NF-κB = nuclear factor-kappa-B; PCR = polymerase chain reaction; RA = rheumatoid arthritis; RF = rheumatoid factor; SNP = single-nucleotide polymorphism; SvdH = Sharp/van der Heijde; TNF-α = tumor necrosis factor-alpha. Arthritis Research & TherapyVol 9 No 2 Fonseca et al. Page 2 of 10(page number not for citation purposes) more than 2 years of DD and radiological damage in patients with less than 10 years of DD. A borderline effect was found between the -238 SNP and HAQ score and radiological damage in patients with 2 to 10 years of DD. An association was also found between haplotypes and the SvdH score for those with more than 10 years of DD. An association was found between some TNF-α promoter SNPs and systemic manifestations, radiological progression, HAQ score, work disability, and joint surgeries, particularly in some classes of DD and between haplotypes and radiological progression for those with more than 10 years of DD.

Calcium pyrophosphate dihydrate crystal arthropathy (CPPA) is a well known but heterogeneous disease with a variable presentation and course. We present a cross-sectional study undertaken in a Portuguese rheumatology unit with the aim of analysing clinical and radiological patterns of CPPA in our population. The study population included 50 patients, 34 (68%) women and 16 (32%) men. The mean age was 69.8 +/- 8.8 years. The onset features were acute arthritis in 19 (38%) patients and chronic joint complaints in 26 (52%); five (10%) patients were asymptomatic at the time of diagnosis, which was based only on radiological findings. The diagnosis was established in 37 (74%) cases by clinical and radiographic features, in eight (16%) by clinical, X-ray and synovial fluid analysis, and in five (10%) by clinical features and fluid analysis. The disease course was characterised by acute episodic arthritis in 16 (32%) patients and by persistent symptoms (with or without synovitis) in 34 (68%). The pattern of CPPA in 20 (40%) patients was pseudo-osteoarthritis with synovitis, pseudo-osteoarthritis without synovitis in nine (18%), pseudogout in nine (18%), monoarthropathy in eight (16%) and pseudorheumatoid arthritis in four (8%). The phosphocalcium balance was altered in nine (18%) cases: six patients had hypercalciuria two hyperphosphaturia, two hypocalciuria, one hypophosphaturia and one hypercalcemia. Five patients had abnormal thyroid hormone levels, but only one presented with clinical hypothyroidism. Four patients showed increased parathormone levels, but only one presented with clinical hyperparathyroidism. Radiographic findings showed that 43 (86%) patients had meniscus calcifications, 20 (40%) radiocarpal and 16 (32%) calcification of the symphysis pubis. The study confirms the clinical variability of the disease in a population of Portuguese patients. The knee meniscus calcifications were the most sensitive single finding for establishing the diagnosis of CPPA. Almost all our patients had sporadic idiopathic CPPA without associated pathological conditions.