A multidisciplinary expert committee was convened as a task force of the EULAR Standing Committee for Clinical Affairs (ESCCA), comprising 18 members including rheumatologists, cardiologists, internists and epidemiologists, representing nine European countries. Problem areas and related keywords for systematic literature research were identified. A systematic literature research was performed using MedLine, Embase and the Cochrane library through to May 2008. Based on this literature review and in accordance with the EULAR’s "standardised operating procedures", the multidisciplinary steering committee formulated evidence-based and expert opinion-based recommendations for CV risk screening and management in patients with inflammatory arthritis.

Annual CV risk assessment using national guidelines is recommended for all patients with RA and should be considered for all patients with AS and PsA. Any CV risk factors identified should be managed according to local guidelines. If no local guidelines are available, CV risk management should be carried out according to the SCORE function. In addition to appropriate CV risk management, aggressive suppression of the inflammatory process is recommended to further lower the CV risk.

Ten recommendations were made for CV risk management in patients with RA, AS and PsA. The strength of the recommendations differed between RA on the one hand, and AS and PsA, on the other, as evidence for an increased CV risk is most compelling for RA.

To compare incidence rates between RA and other chronic arthritides (OCA) 0–24 months after delivery, and to compare the incidence rates within each group 0–24 versus 25–48 months post partum.

Premenopausal women from a Norwegian patient register were linked with the Medical Birth Registry of Norway to study the interval between delivery and time of diagnosis. Cox regression analysis with adjustments for age at delivery and birth order was applied to compare proportions of incident cases of RA and OCA with onset 0–24 months post partum. Poisson regression analysis with adjustment for the population at risk was applied to estimate the incidence rate ratio (IRR) 0–24 versus 25–48 months post partum.

Of 183 RA and 110 patients with OCA diagnosed after delivery, 69 (37.7%) had RA and 31 (28.2%) OCA during the first 24 months post partum (p = 0.09). The IRR (95% CI) for diagnosis during 0–24 months versus 25–48 months was 1.73 (1.11 to 2.70) (p = 0.01) for RA, 1.05 (0.59 to 1.84) (p = 0.86) for OCA. The IRR was 2.23 (1.06 to 4.70) and 1.87 (0.67 to 5.21), respectively, when only considering diagnoses after the first pregnancy. Clinical characteristics were similar within each diagnostic group.

The proportions of incident cases with onset 0–24 months after delivery were not different between RA and OCA. A peak in incidence during 0–24 months was seen in the RA group, both when considering all pregnancies and only the first pregnancy.

Medline was searched via PubMed (1966 to May 2008) for anti-MCV and related terms, arthritis and arthropathies. Studies with anti-MCV, arthritis/arthropathy, and primary data on diagnosis and/or prognosis were included. Their methodological quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS) instrument for diagnostic studies and the modified Hayden list for prognostic studies.

Of 14 eligible studies, 11 included diagnostic data and 3 included prognostic data. No study evaluated anti-MCV as an added diagnostic test to the already available anti-cyclic citrullinated peptide (CCP) and rheumatoid factor serology. One study included the optimal patient spectrum resulting in a sensitivity of 0.59 and specificity of 0.98. A total of 10 diagnostic case-control studies using the same anti-MCV kit showed a sensitivity of 0.64–0.84 and a specificity of 0.79–0.96. This almost equalled the performance of anti-CCP in the same studies. The prognostic evaluation of anti-MCV was limited by differences in study methodology, outcome and statistical modelling. Individual studies showed moderate associations for anti-MCV and radiological progression with the strength of the association comparable to that of anti-CCP.

Study heterogeneity, choice of study population and methodological limitations limited overall conclusions about the true diagnostic and prognostic test performance of anti-MCV. Evidence from the diagnostic case-control studies suggests that anti-MCV may be used as an alternative for anti-CCP.

A cohort of 238 patients with RA was followed longitudinally for 10 years; 125 patients with complete x ray sets were included in the main analyses. Radiographs were scored according to the van der Heijde modified Sharp score (SHS). Patients were analysed for anti-MCV and anti-cyclic citrullinated peptide (CCP), and were genotyped for human leukocyte antigen (HLA)-DRB1 "shared epitope" (SE) and protein tyrosine phosphatase, non-receptor type 22 (PTPN22) 1858T.

Anti-MCV and anti-CCP were strongly associated with regard to status and level. Both antibodies were associated with SE, but only anti-MCV was significantly associated with PTPN22 1858T. A positive anti-MCV test increased the odds of radiographic progression by 7.3 (95% confidence interval (CI) 3.2 to 16.5) compared to 5.7 (95% CI 2.6 to 12.5) for a positive anti-CCP. Presence of MCV antibodies gave an average increase in the total SHS of 30 U compared to an average increase of 25 U for the presence of CCP antibodies. Anti-MCVs were more strongly associated to progression in erosions than joint space narrowing. Associations remained after adjustment for other predictors of radiographic progression. The odds of progression increased with increasing anti-MCV level.

Presence of anti-MCV predicted joint damage, and the strength of this prediction was at least as strong as for anti-CCP. Antibody status showed a stronger association to bone than to cartilage destruction. This study also indicates that higher anti-MCV levels add prognostic information compared to their mere presence or absence.

To study secular trends in baseline health utilities in patients commencing tumour necrosis factor (TNF) blockade for arthritis in clinical practice over 7 years; to address utility changes during treatment; to investigate the influence of previous treatment courses; to study the feasibility of health utility measures and to compare them across diagnostic entities.

EuroQoL 5 dimensions (EQ-5D) utility data were collected from a structured clinical follow-up programme of anti-TNF-treated patients with RA (N = 2554), PsA (N = 574) or spondylarthritides (N = 586). Time trends were calculated. Completer analysis was used.

There were weak or non-significant secular trends for increasing baseline utilities over time for RA, PsA and spondylarthritides. The maximum gain in utilities had already occurred after 2 weeks for all diagnoses and remained stable for patients remaining on therapy. The first and second anti-TNF courses performed similarly.

Utilities at inclusion remained largely unchanged for RA, PsA and spondylarthritides over 7 years. Improvement occurred early during treatment and not beyond 6 weeks at the group level. Improvement during the first course was not consistently greater than the second. There were no major differences between RA, PsA and spondylarthritides. EQ-5D proved feasible and applicable across these diagnoses. These "real world" data may be useful for health economic modelling.

National register data were used to link reproductive histories and later RA hospitalisations in a cohort of 4.4 million Danes. As a measure of relative risk associated with different reproductive histories, ratios of first inpatient RA hospitalisation rates (RRs) were used with 95% confidence intervals (CIs) obtained by Poisson regression analysis.

Overall, 7017 women and 3041 men were admitted to hospital with RA in 1977–2004 (88.8 million person-years). The risk of RA was inversely associated with age at birth of first child in both women and men (p for trend <0.001). Overall, nulliparity and a history of pregnancy loss were not associated with RA risk but, compared with one-child mothers, women with two (RR 0.84; 95% CI 0.78 to 0.90) or three (RR 0.83; 95% CI 0.77 to 0.91) children were at reduced risk. The risk of RA was increased in women with a history of hyperemesis (RR 1.70; 95% CI 1.06 to 2.54), gestational hypertension (RR 1.49; 95% CI 1.06 to 2.02) or pre-eclampsia (RR 1.42; 95% CI 1.08 to 1.84).

One-child mothers and young parents are at increased risk of RA later in life, possibly due to socioeconomic factors. The novel finding of a significantly increased risk of RA in women whose pregnancies were complicated by hyperemesis, gestational hypertension or pre-eclampsia might reflect reduced immune adaptability to pregnancy in women disposed to RA or a role of fetal microchimerism in the aetiology of RA.

Patients receiving stable doses of MTX were randomised to one of six dose groups and received 12 weeks of double-blind pamapimod (up to 300 mg once daily) or matching placebo. The primary efficacy measure was the proportion of patients with >=20% improvement in RA based on the American College of Rheumatology criteria (ACR20) at 12 weeks. Secondary measures were ACR50, Disease Activity Score (DAS)/European League Against Rheumatism (EULAR) responses and the individual ACR core set of parameters. Safety measures included adverse events (AEs), laboratory testing and immunology assessments.

On a background of MTX, the percentage of patients with an ACR20 response at week 12 in the pamapimod groups (31% to 43%) was not significantly different from placebo (34%). Secondary efficacy end points showed a similar pattern. AEs were typically mild and included infections, gastrointestinal disturbances, dizziness and rashes; AEs resulting in discontinuation of study drug were primarily attributed to infections.

In patients with active RA receiving stable doses of MTX, pamapimod showed non-significant improvement in efficacy outcomes compared to placebo.

A multicentre association study consisting of 4 RA case-control series (4397 cases and 2857 controls) and 3 SLE case-control series (591 cases and 2199 shared controls) was conducted. Genotyping was performed using TaqMan genotyping assay for two single nucleotide polymorphisms (SNPs) that showed the best evidence of association in the previous Caucasian studies. Quantifications of TRAF1 and C5 expression were performed with TaqMan expression assay.

Significant differences in allele frequency for both SNPs were observed between RA and control subjects (combined odds ratio = 1.09), while no significant difference was detected between patients with SLE and controls. Interestingly, alleles rs3761847 A and rs10818488 G had increased the risk for RA in the present study, while they decreased the risk in the original studies. A significant difference was found between risk allele carriers and non-carriers of rs10818488 for the expression level of TRAF1 in phorbol myristate acetate-stimulated lymphoblastoid cell lines (p = 0.04).

Association of TRAF1-C5 locus with RA susceptibility was detected in the Japanese populations with modest magnitude, while no significant association was observed for SLE. Significant positive effect of genotype on the expression of TRAF1 might support the genetic association between TRAF1 and RA.

The numbers of patients with pain relief over baseline (>=15%, >=30%, >=50%, >=70%) at 2, 4, 8 and 12 weeks of treatment were obtained using the WOMAC 100 mm visual analogue pain subscale score for each treatment group in seven randomised placebo-controlled trials of etoricoxib in osteoarthritis lasting >=6 weeks. Dropouts were assigned 0% improvement from baseline from then on. The numbers needed to treat (NNTs) were calculated at each level of response and time point.

3554 patients were treated with placebo, etoricoxib 30 mg and 60 mg, celecoxib 200 mg, naproxen 1000 mg or ibuprofen 2400 mg daily. Response rates fell with increasing pain relief: 60–80% experienced minimally important pain relief (>=15%), 50–60% moderate pain relief (>=30%), 40–50% substantial pain relief (>=50%) and 20–30% extensive pain relief (>=70%). NNTs for etoricoxib, celecoxib and naproxen were stable over 2–12 weeks. Ibuprofen showed lessening of effectiveness with time.

Responder rates and NNTs are reproducible for different levels of response over 12 weeks and have relevance for clinical practice at the individual patient level. An average 10 mm improvement in pain equates to almost one in two patients having substantial benefit.

Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures.

A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses >10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53).

MTX, TNF antagonists and prednisone at doses >10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections.

To analyse the effectiveness of RTX versus alternative aTNFs on RA disease activity in different subgroups of patients.

A prospective cohort study of patients with RA who discontinued at least one aTNF and subsequently received either RTX or an alternative aTNF, nested within the Swiss RA registry (SCQM-RA) was carried out. The primary outcome, longitudinal improvement in 28-joint count Disease Activity Score (DAS28), was analysed using multivariate regression models for longitudinal data and adjusted for potential confounders.

Of the 318 patients with RA included; 155 received RTX and 163 received an alternative aTNF. The relative benefit of RTX varied with the type of prior aTNF failure: when the motive for switching was ineffectiveness to previous aTNFs, the longitudinal improvement in DAS28 was significantly better with RTX than with an alternative aTNF (p = 0.03; at 6 months, –1.34 (95% CI –1.54 to –1.15) vs –0.93 (95% CI –1.28 to –0.59), respectively). When the motive for switching was other causes, the longitudinal improvement in DAS28 was similar for RTX and alternative aTNFs (p = 0.40). These results were not significantly modified by the number of previous aTNF failures, the type of aTNF switches, or the presence of co-treatment with a disease-modifying antirheumatic drug.

This observational study suggests that in patients with RA who have stopped a previous aTNF treatment because of ineffectiveness changing to RTX is more effective than switching to an alternative aTNF.

Patients received adalimumab 40 mg every other week in addition to standard therapy in this prospective, 12-week, open-label, uncontrolled study. Four definitions of good clinical response were used: >=50% improvement in American College of Rheumatology response criteria (ACR50), good response according to European League Against Rheumatism (EULAR) guidelines, a >=3-grade improvement in Physician Global Assessment of psoriasis (PGA) and a >=50% improvement in the Nail Psoriasis Severity Index (NAPSI). Response predictors were determined by logistic regression with backward elimination (selection level was 5%).

Of 442 patients, 94% completed 12 weeks of treatment. At week 12, 74%, 51% and 32% of the patients had achieved ACR20, 50 and 70, respectively; 87% and 61% experienced moderate and good responses according to EULAR criteria, respectively. The percentage of patients with PGA results of "clear/almost clear" increased from 34% (baseline) to 68%. The mean NAPSI score was reduced by 44%. No new safety signals were detected. A lower Health Assessment Questionnaire Disability Index (HAQ-DI) score, greater pain assessment, male sex and absence of systemic glucocorticoid therapy were strongly associated with achievement of ACR50 and good response according to EULAR criteria. In addition, greater C-reactive protein concentration and polyarthritis predicted ACR50, and non-involvement of large joints predicted a good response according to EULAR criteria.

Adalimumab was effective in patients with PsA. Lower impairment of physical function, greater pain, male sex and no systemic treatment with glucocorticoids were factors that increased the chance of achieving a good clinical response.

A national prospective registry was designed (Research Axed on Tolerance of bIOtherapies; RATIO) to collect all cases of lymphoma in French patients receiving anti-TNF therapy from 2004 to 2006, whatever the indication. A case–control analysis was conducted including two controls treated with anti-TNF per case and an incidence study of lymphoma with the French population was used as the reference.

38 cases of lymphoma, 31 non-Hodgkin’s lymphoma (NHL) (26 B cell and five T cell), five Hodgkin’s lymphoma (HL) and two Hodgkin’s-like lymphoma were collected. Epstein–Barr virus was detected in both of two Hodgkin’s-like lymphoma, three of five HL and one NHL. Patients receiving adalimumab or infliximab had a higher risk than those treated with etanercept: standardised incidence ratio (SIR) 4.1 (2.3–7.1) and 3.6 (2.3–5.6) versus 0.9 (0.4–1.8). The exposure to adalimumab or infliximab versus etanercept was an independent risk factor for lymphoma in the case–control study: odds ratio 4.7 (1.3–17.7) and 4.1 (1.4–12.5), respectively. The sex and age-adjusted incidence rate of lymphoma was 42.1 per 100 000 patient-years. The SIR was 2.4 (95% CI 1.7 to 3.2).

The two to threefold increased risk of lymphoma in patients receiving anti-TNF therapy is similar to that expected for such patients with severe inflammatory diseases. Some lymphomas associated with immunosuppression may occur, and the risk of lymphoma is higher with monoclonal-antibody therapy than with soluble-receptor therapy.

Fifty-eight patients with RA were treated with rituximab. The clinical response was determined 24 weeks after each treatment course using the Disease Activity Score evaluated in 28 joints (DAS28) and EULAR response criteria. Rituximab serum levels, ARAs and synovial B lineage cell numbers were determined before and after treatment.

Four weeks after treatment rituximab serum levels were highly variable. Low rituximab levels were associated with ARA formation (in five patients (8.6%)) and high baseline erythrocyte sedimentation rate. Interestingly, serum rituximab levels were not related to persistence of synovial B lineage cells or clinical response. Furthermore, response to treatment and re-treatment was similar in ARA-positive and ARA-negative patients.

There is clear variability in serum levels after rituximab treatment, but rituximab levels are not lower in patients with persistence of synovial B lineage cells or lack of clinical response. The current treatment schedule suffices to induce and maintain a clinical response, even when ARAs are formed.

Patients were randomised equally to placebo, CP-690,550 5, 15 or 30 mg twice daily for 6 weeks, with 6 weeks’ follow-up. The patient’s assessment of arthritis pain (pain), patient’s assessment of disease activity, Health Assessment Questionnaire-Disability Index (HAQ-DI) and Short Form-36 (SF-36) were recorded.

At week 6, significantly more patients in the CP-690,550 5, 15 and 30 mg twice-daily groups experienced a 50% improvement in pain compared with placebo (44%, 66%, 78% and 14%, respectively), clinically meaningful reductions in HAQ-DI (>=0.3 units) (57%, 75%, 76% and 36%, respectively) and clinically meaningful improvements in SF-36 domains and physical and mental components.

CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.

50 patients with <=12 weeks of inflammatory symptoms with or without signs had clinical, laboratory and imaging assessments. Diagnosis was recorded at 12 months. Assuming a 15% pre-test probability of IA, post-test probabilities for various assessments were calculated and used to develop a diagnostic algorithm.

All patients positive for rheumatoid factor (RF) and/or cyclic citrullinated peptide (CCP) developed persistent IA, so the added value of PDUS was assessed in the seronegative (RF and CCP negative) group. The probability of IA in a seronegative patient was 6%. The addition of clinical and radiographic features raised the probability of IA to 30% and, with certain ultrasound features, this rose to 94%.

In seronegative patients with early IA, combining PDUS with routine assessment can have a major impact on the certainty of diagnosis.

Disease activity scores from the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study of 118 patients were available for analysis. Before conception (if applicable), at each trimester and at 6, 12 and 26 weeks post partum, levels of the autoantibodies anti-CCP, IgM-RF, IgG-RF and IgA-RF were determined. Responses in disease activity were classified according to European League Against Rheumatism (EULAR) response criteria during pregnancy and post partum, and associated with the presence or absence of autoantibodies.

The median levels of anti-CCP and all subclasses of RF during pregnancy were stable, whereas post partum the levels of anti-CCP, IgM-RF and IgA-RF declined. A significantly higher percentage of women without autoantibodies (negative for anti-CCP and RF) improved compared with women positive for either or both autoantibodies (75% vs 39%, p = 0.01). The occurrence of a flare post partum was comparable between these groups.

Improvement of disease activity of RA during pregnancy was not associated with changes in levels of autoantibodies during pregnancy, however, improvement may occur more frequently in the absence of anti-CCP and RF.

230 patients with active AS who were participating in a randomised controlled trial comparing two infliximab infusion modalities—every 6 weeks (Q6) and on demand (DEM)—were included in an economic evaluation within the trial. Data were collected by phone every 3 months for 1 year. Direct and indirect costs were calculated from a payer perspective. Health-related quality of life was assessed with a general health rating scale. ICERs were calculated for one 20% improvement (ASAS20), for one partial remission and for one quality-adjusted life year (QALY) gained.

The Q6 regimen was significantly more efficacious than the DEM regimen but also more costly (22 388 vs 17 596; p<0.001), because it required significantly more infliximab infusions per patient (8.4 vs 6.2). The ICERs of the Q6 to DEM regimen were 15 841 for one ASAS20 response, 23 296 for one partial remission and 50 760 for one QALY gained.

The administration of infliximab every 6 weeks is cost effective as compared with a DEM regimen; however, the ICER is close to the acceptability threshold of 50 000 for one QALY gained.

NCT 00439283.

In the first part, sera from 24 SSc patients (12 with pulmonary arterial hypertension (PAH) and 12 without) and 36 idiopathic PAH patients, tested in pooled sera for groups of three, were compared with a sera pool from 14 healthy controls (HC). Serum IgG reactivity was analysed by the use of a two-dimensional electrophoresis and immunoblotting technique with normal human fibroblasts antigens. In the second part, serum IgG reactivity for two groups: 158 SSc, 67 idiopathic PAH and 100 HC; and 35 SSc and 50 HC was tested against -enolase from Saccharomyces cerevisiae and recombinant human (rHu) -enolase, respectively, on ELISA.

In the first part, -enolase was identified as a main target antigen of AFA from SSc patients. In the second part, 37/158 (23%) SSc patients, 6/67 (9%) idiopathic PAH patients and 4/100 (4%) HC (p<0.001) had anti-S cerevisiae -enolase antibodies; 12/35 (34%) SSc patients and 3/50 (6%) HC had anti-rHu -enolase antibodies (p = 0.001). In SSc, the presence of anti-S cerevisiae -enolase antibodies was associated with interstitial lung disease (ILD), decreased total lung capacity (73.2% vs 89.7%; p<0.001) and diffusion capacity for carbon monoxide (47.4% vs 62.3%; p<0.001), and antitopoisomerase 1 antibodies (46% vs 21%; p = 0.005) but not anticentromere antibodies (11% vs 34%; p = 0.006). Results were similar with rHu -enolase testing.

In SSc, AFA recognise -enolase and are associated with ILD and antitopoisomerase antibodies.

Plasma ET-1 was quantified by immunoassay in 61 patients with biopsy-confirmed GCA and 16 healthy donors. ET-1, endothelin-converting enzyme (ECE-1) and endothelin receptor (ET_AR and ET_BR) messenger RNA were measured by real-time quantitative reverse transcriptase–PCR in temporal arteries from 35 of these patients and 19 control arteries. Proteins were measured by immunoassay and Western blot.

ET-1 concentration was increased at the protein level in temporal artery samples from GCA patients compared with controls (0.98 (SEM 0.32) vs 0.28 (SEM 0.098) fmol/mg, p = 0.028). ECE-1, ET_AR and ET_BR/actin ratios (Western blot) were also significantly higher in GCA patients. Intriguingly, mRNA expression of ET-1, ECE-1 and both receptors was significantly reduced in GCA lesions compared with control arteries. When investigating mechanisms underlying these results, platelet-derived growth factor and IL-1β, present in GCA lesions, were found to downregulate ET-1 mRNA in cultured human temporal artery-derived smooth muscle cells. Glucocorticoid treatment for 8 days did not result in significantly decreased endothelin tissue concentration (0.87 (SEM 0.2) vs 0.52 (SEM 0.08); p = 0.6). Plasma endothelin concentrations were higher in patients with ischaemic complications (1.049 (SEM 0.48) vs 1.205 (SEM 0.63) pg/ml, p = 0.032).

The endothelin system is increased at the protein level in GCA lesions creating a microenvironment prone to the development of ischaemic complications. Recovery induced by glucocorticoids is delayed, indicating persistent exposure to endothelin during initial treatment.

In vivo efficacy was measured in arthritis of the knee joint induced by the intra-articular injection of recombinant human TNF (rhTNF) in Lewis rats. Cartilage penetration of scFv (ESBA105) and full length IgG (infliximab) were studied in bovine cartilage specimens ex vivo. Tissue penetration, biodistribution and pharmacokinetics of ESBA105 were followed and compared after intra-articular and intravenous administration.

In cell culture, ESBA105 showed similar TNF inhibitory potency to infliximab. In vivo, ESBA105 inhibited rhTNF-induced synovial inflammation in rats with efficacy again comparable to infliximab. An 11-fold molar excess of ESBA105 over rhTNF resulted in 90% inhibition of knee joint swelling, inflammatory infiltrates and proteoglycan loss from cartilage. In ex vivo studies of bovine cartilage, ESBA105 penetrated well into the cartilage whereas infliximab remained on the surface. In vivo, rapid penetration into the synovial tissue, cartilage and surrounding tissues was observed following intra-articular injection of [¹²⁵I]-ESBA105 into the knee joint of rabbits.

ESBA105 potently inhibits inflammation and prevents cartilage damage triggered by TNF. In contrast to a full length IgG, ESBA105 also penetrates into cartilage and can be expected to reverse the TNF-induced catabolic state of articular cartilage in arthritides.

Synovial inflammation was measured using the arthroscopic visual analogue score (VAS) and further validated using immunohistochemistry and flow cytometry. Highly proliferative clonogenic in vivo MSCs were enumerated following fluorescence-activated cell sorting and expansion for 20 population doublings. MSC multipotency was quantified following standard in vitro culture expansion and trilineage differentiation assays. Real-time PCR, flow cytometry and ELISA were used to evaluate pro- and anti-chondrogenic molecules in standard polyclonal synovial MSCs.

The arthroscopic VAS significantly correlated with synovial macrophage infiltration. In RA, synovial MSC chondrogenesis was inhibited in direct relation to VAS (r = –0.777, p<0.05) and reduced compared with control osteoarthritis (OA)-MSCs (p<0.05). In vivo, MSCs resided in the synovial fibroblastic/stromal fraction (CD45^–CD31^–) and were reduced in frequency in relation to VAS (r = –0.695, p<0.05). In RA-MSCs, CD44 levels correlated negatively with inflammation and positively with chondrogenesis (r = –0.830 and r = 0.865, respectively). Cytokine production and Sox9 expression was similar in RA-MSCs and OA-MSCs.

There is a negative relationship between synovial MSC chondrogenic and clonogenic capacities and the magnitude of synovitis in RA. Effective suppression of joint inflammation is therefore necessary for the development of autologous MSC treatments aimed at cartilage regeneration in RA.

Placenta biopsies were obtained from three patients with SSc and four healthy uncomplicated pregnancies after delivery at 34–38 weeks of gestation. The sections were stained with Masson’s trichrome and phosphotungstic-acid-haematoxylin and immunostained for connective tissue growth factor (CTGF), -smooth muscle actin (-SMA), vascular endothelial growth factor (VEGF), placenta growth factor (PlGF) and receptors VEGFR-1 and VEGFR-2.

The pathological findings were signs of decidual vasculopathy, increased syncytiotrophoblast knotting, placental infarcts and villous hypoplasia. Severe and diffuse perivascular and stromal fibrosis of decidua and chorionic villi, and extensive deposition of fibrinoid material around decidual vessels and in intervillous spaces were observed. Strong CTGF expression in the vessel wall, decidual cells and fibroblasts and -SMA+ myofibroblasts were found. VEGF and VEGFR-2 expression was stronger in SSc than in healthy placentas, while VEGFR-1 expression was similar to controls. PlGF immunopositivity was weaker in SSc.

In SSc placentas, severe fibrosis and abnormal vascular remodelling were detected. This may result in reduced blood flow leading to deep sufferance of maternal placenta and possible premature delivery.

A total of 719 Colombian women were included in the present study: 209 had systemic lupus erythematosus, 99 primary Sjögren syndrome, 159 rheumatoid arthritis and 252 were healthy matched controls. Tag single nucleotide polymorphisms (SNPs) and potentially functional variants were typed by TaqMan allele discrimination assays. HLA-DRB1 and HLA-DQB1 typing was performed by reverse dot-blot hybridisation and linkage disequilibrium (LD) with BAK1 SNPs was assessed.

SNPs rs513349 (odds ratio (OR) 0.57, 95% CI 0.46 to 0.72, p = <0.001) and rs5745582 (OR 1.61, 95% CI 1.26 to 2.04, p = <0.001) were associated with the AIRDs included in this study. There was a significant increase of the rs513349G-rs561276C-rs5745582A (GCA) haplotype in each patient cohort as compared to controls (OR 1.95, 95% CI 1.50 to 2.54, p = <0.001). These SNPs were not in LD with HLA-DRB1 or HLA-DQB1 genes.

The results indicate that the BAK1 polymorphisms influence the risk of acquiring AIRDs in the population studied and are consistent with the paradigm that autoimmune diseases are likely to share common susceptibility variants.