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ID PMID Title PublicationDate abstract
24029651 Temporal trends, clinical characteristics, and outcomes of histoplasmosis in a tertiary ca 2014 Mar The impact of highly active antiretroviral therapy (HAART) on the epidemiology of AIDS-associated histoplasmosis in the past decade is poorly defined. Among 100 patients with histoplasmosis in an endemic region between 2000 and 2009, 42 patients were immunocompetent, 32 were infected with HIV, and 26 were non-HIV-immunocompromised patients. The percentage with HIV decreased 67% in 2000-2001 to 18% in 2008-2009 (P = .004), while the proportion of non-HIV immunocompromised patients increased, 8% to 41% (P = .14). Histoplasma antigen was the most sensitive test (73%), whereas potassium hydroxide examination of clinical specimens was the least sensitive test (33%) in all 3 groups. Bronchoalveloar fluid culture (74%) had the highest yield among the cultures. The relapse rate was higher in HIV-infected patients compared to the other 2 groups (P = .04). The epidemiology of histoplasmosis in our endemic area has changed during the era of HAART. Organ transplantation and increasing use of immunosuppressive agents for chronic inflammatory conditions in non-HIV patients now account for most of the cases of histoplasmosis.
23564183 Pharmacogenetics and pharmacogenomics in rheumatology. 2013 Jul Pharmacogenetics and pharmacogenomics deal with possible associations of a single genetic polymorphism or those of multiple gene profiles with responses to drugs. In rheumatology, genes and gene signatures may be associated with altered efficacy and/or safety of anti-inflammatory drugs, disease-modifying antirheumatic drugs (DMARDs) and biologics. In brief, genes of cytochrome P450, other enzymes involved in drug metabolism, transporters and some cytokines have been associated with responses to and toxicity of non-steroidal anti-inflammatory drugs, corticosteroids and DMARDs. The efficacy of biologics may be related to alterations in cytokine, chemokine and FcγR genes. Numerous studies reported multiple genetic signatures in association with responses to biologics; however, data are inconclusive. More, focused studies carried out in larger patient cohorts, using pre-selected genes, may be needed in order to determine the future of pharmacogenetics and pharmacogenomics as tools for personalized medicine in rheumatology.
25248056 Quantitative analysis of elastase and cathepsin G mRNA levels in peripheral blood CD14(+) 2014 Nov In rheumatoid arthritis (RA) activity of serine proteases is an important factor contributing to destructive changes in the joints. The aim of this study was to compare elastase (ELANE) and cathepsin G (CTSG) mRNA levels in peripheral blood CD14(+) cells obtained from RA patients, healthy subjects (HS) and patients with osteoarthritis (OA). CD14(+) cells were isolated from peripheral blood by positive magnetic selection. The expression levels of ELANE and CTSG were determined by quantitative real-time PCR. ELANE mRNA expression was significantly higher in RA patients when compared to HS (p<0.001) and OA patients (p<0.001). The results suggest that in RA, peripheral blood CD14(+) cells express serine protease mRNA as a result of systemic mechanisms probably related to inflammation/cytokines before entering inflamed joints.
24480141 Connective tissue disease-associated interstitial pneumonia and idiopathic interstitial pn 2014 Feb Interstitial lung diseases (ILDs) are increasingly recognized in patients with systemic diseases. Patients with early ILD changes may be asymptomatic. Features of ILD overlap among systemic diseases and with idiopathic variety. High-resolution computed tomography plays a central role in diagnosing ILDs. Imaging features are often nonspecific. Therapy- and complication-related lung changes would pose difficulty in diagnosing and classifying an ILD. Biology and prognosis of secondary ILDs may differ between different disease-related ILDs and idiopathic variety. Combination of clinical features, serological tests, pulmonary and extrapulmonary imaging findings, and pathology findings may help to diagnose ILDs.
24447777 Is rheumatoid arthritis a B-cell haematological disease with a predilection for the joints 2014 Mar B-cell depleting therapy (BCDT) is effective in suppressing synovitis and erosions in rheumatoid arthritis suggesting that a cell of the B-lymphocyte lineage is critical in the pathogenesis of this disease. Non-Hodgkins lymphoma (NHL) also responds to BCDT but multiple myeloma (MM), does not as cells have differentiated beyond the CD20-bearing stage. However, there are similarities between B-NHL, MM and RA that suggest all 3 conditions could be initiated and perpetuated by the same cellular players. Numerous plasma cells and B cells are present within rheumatoid synovial membrane, and subarticular bone where they contribute to osteitis. On MRI scans this appears as bone oedema, which has been demonstrated to precede the development of bone erosions. Plasma cell clonality has been detected within RA synovial membrane and bone marrow. It is proposed that RA could represent a "forme fruste" of a B cell neoplastic condition, with production of autoantibodies that target a self-antigen within the joint. The activation of rheumatoid bone osteoclasts by anticitrullinated protein antibodies supports this theory. The erosions of RA would have parallels with the lytic lesions of MM but autoantigen targeting dictates that erosions occur at joint margins. This theory is discussed from rheumatologic and haematologic perspectives.
24371023 Comparison of the short-term results of the first and last 50 Scandinavian total ankle rep 2014 Apr BACKGROUND: Total ankle replacement (TAR) is presently considered to be an acceptable alternative to ankle fusion for patients with debilitating conditions of the ankle. The placing of a total ankle prosthesis is a technically demanding procedure. We hypothesized that the challenging conditions could cause a longer learning curve (>30 cases), and therefore the short-term results of the first and the last 50 cases in a consecutive series of 134 cases were compared. METHODS: The first and last consecutive 50 cases by a single surgeon in a series of 134 Scandinavian Total Ankle Replacements (STAR; Waldemar Link, Hamburg, Germany), inserted between May 1999 and May 2008, were evaluated. Operation characteristics, clinical outcome (Foot Function Index [FFI], Kofoed score), complications, and the component alignment on X-rays were assessed. The outcome measures for both groups were compared using independent Student t tests, chi-square tests, and nonparametric alternatives (P < .05). RESULTS: Surgery time decreased from a median of 125 (83-160) to 100 (65-170) minutes (P < .001), and fewer perioperative complications were observed (12 vs 4, P = .04). The sagittal alignment of the tibial component was closer to normal in the last series (P < .001). The clinical outcome did not differ between the 2 series (median FFI: 32 [0-74] vs 25 [0-75], Kofoed score: median 71 [21-96] vs 80.5 [23-100]). The major underlying pathology did change from rheumatoid arthritis (60%) to osteoarthritis (44%; P = .002). No differences in type and number of complications were reported. CONCLUSION: The surgery time did decrease, there were fewer perioperative fractures, and the tibial component orientation improved, suggesting the presence of a learning curve. Operative experience and a shift in major underlying pathology did not influence clinical outcome. In view of this learning curve we suggest more restrictive patient selection for at least the first 50 TARs. LEVEL OF EVIDENCE: Level III, comparative series.
25299001 Efficacy and safety of rituximab in elderly patients with rheumatoid arthritis enrolled in 2014 Sep OBJECTIVE: The aim of this study was to compare the efficacy and safety of rituximab (RTX) as a function of patient age. METHODS: We included all rheumatoid arthritis patients in the AutoImmunity and Rituximab registry with a 2-year followup. RESULTS: Of the 1,709 patients, 191 were age ≥75 years, 417 were ages 65–74 years, 907 were ages 50–64 years, and 194 were age <50 years. At baseline, the elderly and very elderly patients presented with longer disease duration, a higher incidence of erythrocyte sedimentation rate and C-reactive protein level, a lower incidence of previous tumor necrosis factor α (TNFα) therapy, and a smaller number of previously used TNFα agents. Disease activity, rheumatoid factor (RF), or anti–cyclic citrullinated peptide (anti-CCP) antibodies and corticosteroid therapy were not statistically different among the groups. At 24 months, no significant difference was shown among the groups for RTX discontinuation rates (36.1% if age <50 years, 32.6% if ages 50–64 years, 34.5% if ages 65–74 years, and 32.5% if age >75 years). The reasons for discontinuation (inefficacy, adverse events) were the same in all 4 groups. Infections were more common in the elderly. Patients ages 65–75 years were more likely to be good responders than nonresponders at 1 year of followup than patients age ≥75 years (odds ratio 3.81, 95% confidence interval 1.14–12.79) after adjustment on disease duration, RF/anti-CCP positivity, corticosteroids, anti-TNF use, and baseline Disease Activity Score in 28 joints (DAS28). After the sixth month, the decrease in DAS28 score was less marked in the population age >75 years than in the group age <50 years. CONCLUSION: The efficacy and safety of RTX is affected by age.
24305643 Functional impact of a spectrum of interstitial lung abnormalities in rheumatoid arthritis 2014 Jul BACKGROUND: Approximately 10% of patients with rheumatoid arthritis (RA) have interstitial lung disease (ILD), and one-third have subclinical ILD on chest CT scan. In this study, we aimed to further characterize functional decrements in a spectrum of RA-associated ILD. METHODS: All subjects were enrolled in the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study (BRASS). The presence of interstitial lung abnormalities (ILAs) on clinically indicated chest CT scans was determined using a previously validated sequential reading method. Univariate and multivariate analyses were used to assess the association between degree of ILAs and physiologic, functional, and demographic variables of interest. RESULTS: Of 1,145 BRASS subjects, 91 subjects (8%) were included in this study. Twelve had radiologically severe ILAs, 34 had ILAs, and 38 had no ILAs on CT scan. Subjects with radiologically severe ILAs were older (P = .0037), had increased respiratory symptoms (cough, P = .027; dyspnea, P = .010), and more severe RA disease (rheumatoid factor, P = .018; total swollen joints, P = .046) compared with subjects with no ILAs. Participants also had a trend toward having an increased smoking history (P = .16) and having lower FVC % predicted (77% vs 94%, P = .097) and diffusion capacity of carbon monoxide % predicted (52% vs 77%, P = .068). Similar but attenuated increases in respiratory symptoms, functional decrements, and RA disease severity were observed in subjects with ILAs compared with those with no ILAs. CONCLUSIONS: We have shown that patients with RA have varying degrees of ILAs that are associated with a spectrum of functional and physiologic decrements. Our findings suggest that improved risk stratification and detection of ILAs will provide a therapeutic window that could improve RA-ILD outcomes.
24515531 Social security work disability and its predictors in patients with fibromyalgia. 2014 Sep OBJECTIVE: To determine prevalence and incidence of US Social Security Disability and Supplemental Security Income (SSD) in patients with fibromyalgia and to investigate prediction of SSD. METHODS: Over a mean of 4 years (range 1-13 years), we studied 2,321 patients with physician-diagnosed fibromyalgia (prevalent cases) and applied modified American College of Rheumatology (ACR) 2010 research criteria to identify criteria-positive patients. RESULTS: During the study, 34.8% (95% confidence interval [95% CI] 32.9-36.8%) of fibromyalgia patients received SSD. The annual incidence of SSD among patients not receiving SSD at study enrollment was 3.4% (95% CI 3.0-3.9%), and 25% were estimated to be work disabled at 9.0 years of followup. By comparison, the prevalence of SSD in rheumatoid arthritis (RA) patients with concomitant fibromyalgia was 55.6% (95% CI 54.3-57.0%) and was 42.4% in osteoarthritis (OA). By study conclusion, 31.4% of SSD awardees were no longer receiving SSD. In univariate models, incident SSD in patients with fibromyalgia was predicted by sociodemographic measures and by symptom burden; but the strongest predictor was functional status (Health Assessment Questionnaire disability index [HAQ DI]). In multivariable models, the HAQ DI and the Short Form 36-item health survey physical and mental component summary scores, but no other variables, predicted SSD. Fibromyalgia criteria-positive patients had more SSD, but the continuous scale, polysymptomatic distress index derived from the ACR criteria was a substantially better predictor of SSD than a criteria-positive diagnosis. CONCLUSION: The prevalence of SSD is high in fibromyalgia, but not higher than in RA and OA patients who satisfy fibromyalgia criteria. The best predictors of work disability are functional status variables.
24385024 The influence of polygenic risk scores on heritability of anti-CCP level in RA. 2014 Mar The objective of this study was to study genetic factors that influence quantitative anticyclic citrullinated peptide (anti-CCP) antibody levels in RA patients. We carried out a genome-wide association study (GWAS) meta-analysis using 1975 anti-CCP+ RA patients from three large cohorts, the Brigham Rheumatoid Arthritis Sequential Study (BRASS), North American Rheumatoid Arthritis Consortium (NARAC) and the Epidemiological Investigation of RA (EIRA). We also carried out a genome-wide complex trait analysis (GCTA) to estimate the heritability of anti-CCP levels. GWAS-meta-analysis showed that anti-CCP levels were most strongly associated with the human leukocyte antigen (HLA) region with a P-value of 2 × 10(-11) for rs1980493. There were 112 SNPs in this region that exceeded the genome-wide significance threshold of 5 × 10(-8), and all were in linkage disequilibrium (LD) with the HLA- DRB1*03 allele with LD r(2) in the range of 0.25-0.88. Suggestive novel associations outside of the HLA region were also observed for rs8063248 (near the GP2 gene) with a P-value of 3 × 10(-7). None of the known RA risk alleles (∼52 loci) were associated with anti-CCP level. Heritability analysis estimated that 44% of anti-CCP variation was attributable to genetic factors captured by GWAS variants. In summary, anti-CCP level is a heritable trait, and HLA-DR3 and GP2 are associated with lower anti-CCP levels.
25015955 Folate receptor-β constitutes a marker for human proinflammatory monocytes. 2014 Oct Activated macrophages are commonly involved in the pathogenesis of inflammatory and autoimmune diseases and have been frequently reported to overexpress FR-β. Although FR-targeted therapies aimed at eliminating activated macrophages have shown promise for treating inflammatory diseases, little work has been performed to evaluate whether other hematopoietic cells might also express FR-β. Analysis of peripheral blood cells with a mAb to human FR-β reveals that only monocytes express FR-β. Molecular characterization of these circulating monocytes further demonstrates that solely the classic/proinflammatory subset (CD14(high)CD16(-)) expresses the FR and that only CD14(high)CD16(-) FR-β(+) monocytes also display the ability to bind folate-linked molecules. Confirmation that this subset of monocytes indeed constitutes the proinflammatory subpopulation was obtained by demonstrating coexpression of FR-β with other proinflammatory markers, including CCR2 and HLA-DR. Synovial monocytes from the joints of patients with RA were also shown to express FR-β. As inhibition of the chemotaxis of proinflammatory monocytes into sites of inflammation has been explored frequently as a means of controlling autoimmune diseases, demonstration that FR-β is uniquely expressed on this proinflammatory subpopulation offers a new strategy to suppress migration of inflammatory monocytes into sites of inflammation.
24285495 Drug survival on TNF inhibitors in patients with rheumatoid arthritis comparison of adalim 2015 Feb OBJECTIVE: To compare drug survival on adalimumab, etanercept and infliximab in patients with rheumatoid arthritis (RA). METHODS: Patients with RA (n=9139; 76% women; mean age 56 years) starting their first tumour necrosis factor (TNF) inhibitor between 2003 and 2011 were identified in the Swedish Biologics Register (ARTIS). Data were collected through 31 December 2011. Drug survival over up to 5 years of follow-up was compared overall and by period of treatment start (2003-2005/2006-2009; n=3168/4184) with adjustment for age, sex, education, period, health assessment questionnaire (HAQ), disease duration, concomitant disease modifying antirheumatic drug (DMARD) treatment and general frailty (using hospitalisation history as proxy). RESULTS: During 20 198 person-years (mean/median 2.2/1.7 years) of follow-up, 3782 patients discontinued their first biological (19/100 person-years; 51% due to inefficacy, 36% due to adverse events). Compared with etanercept, infliximab (adjusted HR 1.63, 95% CI 1.51 to 1.77) and adalimumab initiators had higher discontinuation rates (1.26, 95% CI 1.16 to 1.37), and infliximab had a higher discontinuation rate than adalimumab (1.28, 95% CI 1.18 to 1.40). These findings were consistent across periods, but were modified by time for adalimumab versus etanercept (p<0.001; between-drug difference highest the 1st year in both periods). The discontinuation rate was higher for starters in 2006-2009 than 2003-2005 (adjusted HR 1.12, 95% CI 1.04 to 1.20). The composition of 1-year discontinuations also changed from 2003-2005 vs 2006-2009: adverse events decreased from 45% to 35%, while inefficacy increased from 43% to 53% (p<0.001). CONCLUSIONS: Discontinuation rates were higher for infliximab compared with adalimumab and etanercept initiators, and for adalimumab versus etanercept during the 1st year. Discontinuation rates increased with calendar period, as did the percentage discontinuations due to inefficacy.
25257807 Do rheumatologists know best? An outcomes study of inconsistent users of disease-modifying 2015 Feb OBJECTIVE: Current recommendations advocate treatment with disease-modifying anti-rheumatic drugs (DMARDs) in all patients with active rheumatoid arthritis (RA). We analyzed short-term disease outcome in patients according to the consistency of DMARD use in a clinical rheumatology cohort. METHODS: Patients in an RA registry (n = 617) were studied for DMARD use at semi-annual study time points during the first 18 months of follow-up and were divided into 4 groups according to the number of study time points with any DMARD use [0-1 study time points (n = 31), 2 study time points (n = 24), 3 study time points (n = 77), and 4 study time points (n = 485)]. The primary outcome analyses were performed at 24 months and included Disease Activity Score 28 (DAS28-CRP), modified Health Assessment Questionnaire (MHAQ) change, Short Form Health Survey-12 physical and mental summary scores (SF-12 PCS, SF-12 MCS), EuroQol 5-Dimensional health index (EQ-5D), and radiographic progression. Unadjusted, adjusted, and analyses stratified for seropositivity and disease activity were performed. A secondary analysis investigated 36-month outcomes. RESULTS: No significant 24-month outcome differences could be found between the DMARD use categories. For seropositive patients, there was evidence of a linear trend for SF-12 PCS (p = 0.02) and EQ-5D (p = 0.01) with worse outcomes for inconsistent DMARD users. At 36 months, there was a linear trend for higher DAS28-CRP scores for inconsistent users (p < 0.01). CONCLUSIONS: Overall, we found poor correlation between inconsistent DMARD use and short-term disease outcome. However, outcome in the longer term could be negatively influenced by inconsistent DMARD use, as well as short-term outcome in seropositive patients.
24842477 Pharmacokinetics, efficacy and safety profiles of etanercept monotherapy in Japanese patie 2015 Mar Abstract Conventional synthetic disease-modifying anti-rheumatic drugs, including methotrexate, may not be tolerated by all patients with rheumatoid arthritis (RA), and limited international data for etanercept (ETN) monotherapy are available. The aim of this review was to summarize the clinical program for ETN monotherapy in Japanese patients with RA, which has included a pharmacokinetic study, clinical trials for registration, long-term studies, and once-weekly dosing studies. Pharmacokinetic results showed that serum concentrations of ETN were linear with dose levels and were similar to other international studies. Across interventional studies, 652 Japanese patients with active RA were treated with ETN. In the registration studies, ETN treatment led to consistent improvement in American College of Rheumatology 20/50/70 scores, European League Against Rheumatism Good Response, Disease Activity Score 28 erythrocyte sedimentation rate remission, and Health Assessment Questionnaire disability index. In the long-term studies, efficacy was maintained for up to 180 weeks. Similar results were seen in the once-weekly studies. Across the studies, more than 870 patient-years of exposure to ETN were recorded. Discontinuations owing to lack of efficacy or adverse events were modest and no new safety signals were recorded. These studies demonstrated that ETN monotherapy is efficacious and well-tolerated in Japanese patients with RA.
23456366 [Ultrasound in rheumatology. What's new?]. 2013 Mar Ultrasound has become an established imaging modality in rheumatology and is now indispensible in the clinical routine. In the last few years the technology has remarkably improved and new areas of application have been introduced. This review provides an overview of the innovations that are relevant in rheumatologic practice.
23395019 Prevention of complications in shoulder arthroplasty: understanding options and critical s 2013 Total shoulder arthroplasty provides reliable pain relief of osteoarthritic shoulder pain. The keys to success with shoulder arthroplasty are adhering to appropriate indications, understanding the surgical implications of various pathologies, and applying good surgical technique. Many complications of total shoulder arthroplasty may be avoided with good preoperative preparation. Some key surgical steps that may help avoid the more common complications include proper patient positioning, adequate soft-tissue releases for rebalancing, identification of the axillary nerve, correction of glenoid version, the adjustment of humeral component size and version as needed for stability, and meticulous subscapularis repair. Additional precautions can include postoperative immobilization to protect soft-tissue repairs followed by structured rehabilitation.
24630861 Survival and quality of life in rheumatoid arthritis-associated interstitial lung disease 2014 May BACKGROUND: Patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) have increased mortality with limited treatment options. We set out to examine post-transplant survival in RA-ILD patients compared with patients with idiopathic pulmonary fibrosis (IPF) and scleroderma-associated ILD (SSc-ILD). We also describe post-transplant quality of life (QoL) outcomes in RA-ILD. METHODS: A retrospective review was performed on lung transplantation (1989 to 2011) among patients with RA-ILD, IPF (group-matched for age and transplant year) and SSc-ILD. Cumulative survival after transplantation was estimated by the Kaplan-Meier method and compared between groups using the log-rank test. The 36-item Medical Outcomes Survey Short Form (SF-36) and the St. George's Respiratory Questionnaire (SGRQ) scores, before and after lung transplantation, were analyzed. RESULTS: Overall, 10 patients with RA-ILD, 53 with IPF and 17 with SSc-ILD underwent lung transplantation with ages (mean ± SD) of 59.4 ± 5.6, 61.0 ± 4.0 and 45.4 ± 12.7 years, respectively. Cumulative survival rates at 1-year post-transplant for the RA-ILD, IPF and SSc-ILD groups were 67%, 69% and 82%, respectively, and there was no significant difference among groups in age- and gender-adjusted analyses. Among the RA-ILD patients, mean SF-36 physical component summary scores improved from 22.4 ± 8.1 to 32.2 ± 12.9 (p = 0.1), SF-36 mental component summary scores improved from 44.7 ± 15.3 to 54.9 ± 4.8 (p = 0.19) and SGRQ total scores improved from 70.4 ± 16.1 to 36.0 ± 18.5 (p = 0.03). CONCLUSIONS: After lung transplantation, RA-ILD and IPF patients have similar survival rates. Further, in RA-ILD patients, lung transplantation appears to result in a significant improvement in QoL with regard to respiratory symptoms. These data suggest that lung transplantation should be considered in patients with end-stage RA-ILD.
23914907 Association of interleukin-18 (-137G/C) polymorphism with rheumatoid arthritis and systemi 2014 Jan BACKGROUND: Recent studies have suggested that interleukin (IL)-18 gene (-137G/C) polymorphism is associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). However, other studies did not confirm this correlation. OBJECTIVE: The objective of this study was to evaluate the relationships of IL-18 -137G/C and RA and SLE using a meta-analysis. METHODS: Pubmed, Embase and Cochrane library databases were systemically searched. Data were extracted by two independent reviewers and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. RESULTS: In RA, the overall ORs and 95% CIs of -137C were 1.03, 0.88-1.22 (p=0.391); 1.22, 0.89-1.68 (p=0.020) and 1.06, 0.93-1.21 (p=0.110) in dominant, recessive, and additive models, respectively. Furthermore, in SLE, the overall ORs and 95% CIs of -137C were 1.10, 0.94-1.29 (p=0.980); 1.21, 0.91-1.60 (p=0.010) and 1.10, 0.97-1.24 (p=0.454) in dominant, recessive, and additive models, respectively. IL-18 -137G/C could increase the risk of RA and SLE. No publication bias was found in this meta-analysis. After population stratification analysis, under recessive model, the pooled ORs and 95% CIs of -137C were 1.14, 0.82-1.60 (p=0.008) and 1.01, 0.66-1.55 (p=0.004) in European RA patients and Asian SLE patients, respectively. CONCLUSIONS: This meta-analysis showed that IL-18 -137G/C was a risk factor for RA and SLE, especially for RA in Europeans and SLE in Asians.
24116744 Recognition of new citrulline-containing peptide epitopes by autoantibodies produced in vi 2014 Feb Anti-citrullinated peptide/protein antibodies (ACPAs) are highly sensitive and specific markers of rheumatoid arthritis (RA). Identification of peptide epitopes that may detect different subgroups of RA patients might have diagnostic and prognostic significance. We have investigated citrulline- and arginine-containing peptide pairs derived from filaggrin, collagen or vimentin, and compared this citrulline-peptide panel with the serological assays conventionally used to detect ACPAs. Furthermore, we studied if the same citrulline-peptides identify antibody-secreting cells in in vitro cultures of RA B cells. Recognition of citrulline- and arginine-containing filaggrin, vimentin and collagen peptide epitopes were tested by Multipin ELISA system, by indirect ELISA and by a peptide-specific microarray. B cells were purified from blood by negative selection; antibody-producing cells were enumerated by ELISPOT assay. The panel composed of citrulline-peptide epitopes of filaggrin, collagen and vimentin was recognized by RA sera with a sensitivity and specificity comparable with the currently used tests. Moreover, the combined citrulline-peptide panel including the new short epitope peptide of filaggrin, fil311-315, also identified nearly one-third of RA cases that were negative for antibodies against cyclic citrullinated peptides, mutated citrullinated vimentin or for rheumatoid factor. The results with the peptide-specific microarray have shown that although most ACPAs recognizing the four citrulline peptides are IgG, some of them specifically recognizing citrulline-containing filaggrin peptides (fil311-315 and fil306-326) are IgM, and so may be produced either by newly formed activated B cells or by unswitched B memory cells. Furthermore, the citrulline-peptides of filaggrin and vimentin detect ACPA-producing cells, and so could also be applied to study the B cells of RA patients.
24495663 Lack of hepatitis B virus reactivation after anti-tumour necrosis factor treatment in pote 2014 Jun BACKGROUND: Hepatitis B virus (HBV) reactivation in patients positive for antibody to HB core antigen (anti-HBc), negative for HB surface antigen (HBsAg) and HBV-DNA (potential occult HBV carriers), treated with anti-tumor necrosis factor (TNF)α, is a debated question. The aim of the study was to evaluate the safety of anti-TNFα therapy in anti-HBc positive/HBsAg negative subjects with rheumatoid arthritis (RA) and spondyloarthropathy (SpA). METHODS: All consecutive HBsAg negative RA and SpA outpatients referring to the Immuno-Rheumatology Institute at the S. Andrea hospital, Sapienza, University of Rome who had to undergo anti-TNFα therapy. RESULTS: Among the 169 enrolled subjects, 20 (12%) were potential occult HBV carriers (anti-HBc positive, HBsAg and HBV-DNA negative patients with or without anti-HBs). During the follow-up (mean ± SD 45 ± 22 months), aminotransferases and HBV-DNA, tested every two and six months respectively, did not change. CONCLUSION: This study confirms the substantial safety of anti-TNFα therapy in potential occult HBV carriers RA and SpA patients.