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ID PMID Title PublicationDate abstract
23675837 Anti-arthritic activity of ethanol extract of Fagopyrum cymosum with adjuvant-induced arth 2013 Jun CONTEXT: Fagopyrum cymosum (Trey.) Meisn (Polygonaceae) (EFC) has long been used as a folk medicine to treat various ailments of the lung, dysentery and rheumatism in China. OBJECTIVE: The present study evaluated the anti-arthritic effect of 95% ethanol extract of EFC (extract of Fagopyrum cymosum). MATERIALS AND METHODS: The anti-arthritic activity was investigated by adjuvant arthritic (AA) rat model induced by Freund's complete adjuvant (FCA). The AA rats were randomly separated into different groups and then treated with EFC (40, 80 and 160 mg/kg) from day 7 to day 28 after immunization. Arthritis was evaluated by hind paw swelling, polyarthritis index, body weight and index of immune organs. In addition, the severity of arthritis in the knee joints was evaluated by histopathological and hemorheological examination. The levels of interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-α) in the serum were assessed by ELISA. RESULTS: The high dose level of EFC (160 mg/kg) significantly suppressed the swelling of hind paw of AA rats (p < 0.01) and inhibited their body weight loss (p < 0.01). Based on histopathological examination, all EFC groups showed great amelioration compared with the model group. EFC (80 and 160 mg/kg) also decreased the plasma viscosity in different shear rates (p < 0.01). Moreover, EFC significantly reduced the production of IL-1 and TNF-α in the serum of AA (p < 0.01). DISCUSSION AND CONCLUSION: This study provides a scientific basis for the claims that F. cymosum is effective in preventing and suppressing the development and progression of experimental arthritis, with reductions in inflammatory response.
24782175 Periodontitis and Porphyromonas gingivalis in patients with rheumatoid arthritis. 2014 May OBJECTIVE: To examine the degree to which shared risk factors explain the relationship of periodontitis (PD) to rheumatoid arthritis (RA) and to determine the associations of PD and Porphyromonas gingivalis with pathologic and clinical features of RA. METHODS: Patients with RA (n = 287) and patients with osteoarthritis as disease controls (n = 330) underwent a standardized periodontal examination. The HLA-DRB1 status of all participants was imputed using single-nucleotide polymorphisms from the extended major histocompatibility complex. Circulating anti-P gingivalis antibodies were measured using an enzyme-linked immunosorbent assay, and subgingival plaque was assessed for the presence of P gingivalis using polymerase chain reaction (PCR). Associations of PD with RA were examined using multivariable regression. RESULTS: Presence of PD was more common in patients with RA and patients with anti-citrullinated protein antibody (ACPA)-positive RA (n = 240; determined using the anti-cyclic citrullinated peptide 2 [anti-CCP-2] test) than in controls (35% and 37%, respectively, versus 26%; P = 0.022 and P = 0.006, respectively). There were no differences between RA patients and controls in the levels of anti-P gingivalis or the frequency of P gingivalis positivity by PCR. The anti-P gingivalis findings showed a weak, but statistically significant, association with the findings for both anti-CCP-2 (r = 0.14, P = 0.022) and rheumatoid factor (RF) (r = 0.19, P = 0.001). Presence of PD was associated with increased swollen joint counts (P = 0.004), greater disease activity according to the 28-joint Disease Activity Score using C-reactive protein level (P = 0.045), and higher total Sharp scores of radiographic damage (P = 0.015), as well as with the presence and levels of anti-CCP-2 (P = 0.011) and RF (P < 0.001). The expression levels of select ACPAs (including antibodies to citrullinated filaggrin) were higher in patients with subgingival P gingivalis and in those with higher levels of anti-P gingivalis antibodies, irrespective of smoking status. Associations of PD with established seropositive RA were independent of all covariates examined, including evidence of P gingivalis infection. CONCLUSION: Both PD and P gingivalis appear to shape the autoreactivity of RA. In addition, these results demonstrate an independent relationship between PD and established seropositive RA.
25030201 Association between interleukin-6 gene polymorphisms and rheumatoid arthritis in Chinese H 2014 Jul 17 The aim of this study was to investigate the possible association in the interleukin-6 (IL-6) gene with Rheumatoid arthritis (RA) in Chinese Han population from Shandong Province. Target regions of IL-6 gene were amplified by polymerase chain reaction (PCR) and genotyped. A logistic regression analysis was performed to detect potential associations in our case-control sample, the odd ratio(OR) and 95% confidence intervals(CIs) were calculated. Furthermore, we systematically tracked all the published studies in the field and performed a meta-analysis for the single nucleotide polymorphisms (SNPs) under study. 256 RA patients and 331 healthy controls were recruited into the case-control study. We found allele frequencies of rs1800795, rs1800797 and rs1474347 in RA patients differ from control subjects (P = 0.016, 0.024, 0.020, respectively). Significant difference was observed in haplotype frequencies of GCCGCT between RA patients and controls (P = 0.0001, OR = 4.066, 95%CI = 1.891 ~ 8.746), while GGCGCT frequencies was found lower in RA than controls (P = 0.006, OR = 0.669, 95%CI = 0.501 ~ 0.894). The results of the meta-analysis showed association polymorphism within the IL-6 promoter with RA. These findings suggest that rare IL-6 gene polymorphisms may associate with RA susceptibility in Han Chinese populations; however further studies are needed to assess the validity of the association of IL-6 with RA.
23419427 The problem of choice: current biologic agents and future prospects in RA. 2013 Mar The introduction of biologic agents to clinical practice has had a major bearing on the treatment of patients with chronic inflammatory diseases such as rheumatoid arthritis. These drugs have the potential to improve the outcome of disease and the quality of life for patients. However, clinical criteria alone are inadequate for determining which therapy is most appropriate for an individual patient. Furthermore, why a particular drug is effective in a particular patient, or indeed in any patient, but is ineffective for other individuals, is often unknown. In this Review, we provide an overview of biologic therapies currently available for patients with rheumatoid arthritis, and discuss why certain immunological regulators represent potential targets for intervention. Current agents can be clustered into three major types: cytokine blockers, lymphocyte-targeting agents, and small-molecule inhibitors of signal transduction pathways. We differentiate among the modes of action of each of these types of therapy and consider the challenges associated with their use in clinical practice.
25292347 Effect of anti-tumor necrosis factor alpha treatment of rheumatoid arthritis and chronic k 2015 Apr Although chronic kidney disease (CKD) may constitute a chronic inflammatory state indicated by elevated inflammatory mediators such as tumor necrosis factor alpha (TNF-α), the impact of anti-TNF-α therapy on progression of CKD in patients with rheumatoid arthritis (RA) is unclear. Seventy patients with RA and CKD were retrospectively analyzed. Outcomes were evaluated using the difference in the annual change of estimated glomerular filtration rate (eGFR) between patients treated with anti-TNF-α or without. Anti-TNF-α therapy significantly decreased disease activity score (DAS) 28 from 5.32 ± 0.78 to 3.59 ± 0.85 (p < 0.001). There was a tendency toward stabilization of eGFR after a mean of 2.9 ± 1.1 years from 50.3 ± 8.4 ml/min/1.73 m(2) to 54.5 ± 16.0 ml/min/1.73 m(2) in patients received anti-TNF-α therapy along with decreased DAS28 (p = 0.084). Conversely, eGFR decreased significantly in patients not receiving anti-TNF-α therapy after a mean of 2.8 ± 1.7 years from 52.6 ± 7.5 ml/min/1.73 m(2) to 46.5 ± 11.5 ml/min/1.73 m(2) (p = 0.041) without significant DAS28 change (p = 0.078). The annual change of eGFR was significantly different between patients treated with anti-TNF-α drugs and without (2.0 ± 7.0 ml/min/1.73 m(2)/year vs. -1.9 ± 4.0 ml/min/1.73 m(2)/year; difference in mean vs. -3.9 ± 7.3 ml/min/1.73 m(2)/year; p = 0.006). Use of anti-TNF-α drugs was significantly associated with positive annual change of eGFR in multivariate logistic regression analysis (p = 0.019). Among patients with RA and CKD, treatment with anti-TNF-α drugs was associated with less renal function decline. Anti-TNF-α drugs may be beneficial for managing RA combined with CKD.
25110678 Effects of anti-TNF alpha drugs on disability in patients with rheumatoid arthritis: long- 2014 This study involving 1033 patients with RA confirms the effectiveness of etanercept, adalimumab, and infliximab in reducing RA-related disability even in patients with a history of highly active and longstanding RA. Moreover, we found that the improvement in disability was biphasic, with a marked improvement during the first year of anti-TNF therapy, followed by slower but significant recovery over the subsequent four years.
23903050 Overview of models, methods, and reagents developed for translational autoimmunity researc 2013 The common marmoset (Callithrix jacchus) is a small-bodied Neotropical primate and a useful preclinical animal model for translational research into autoimmune-mediated inflammatory diseases (AIMID), such as rheumatoid arthritis (RA) and multiple sclerosis (MS). The animal model for MS established in marmosets has proven their value for exploratory research into (etio) pathogenic mechanisms and for the evaluation of new therapies that cannot be tested in lower species because of their specificity for humans. Effective usage of the marmoset in preclinical immunological research has been hampered by the limited availability of blood for immunological studies and of reagents for profiling of cellular and humoral immune reactions. In this paper, we give a concise overview of the procedures and reagents that were developed over the years in our laboratory in marmoset models of the above-mentioned diseases.
23592565 Impact of statin use on lipid levels in statin-naive patients with rheumatoid arthritis ve 2013 Oct OBJECTIVE: To examine lipid profiles among statin-naive patients with rheumatoid arthritis (RA) and those without RA before and after the initiation of statins. METHODS: Information regarding lipid measures and statin use was gathered in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria first met between January 1, 1988 and January 1, 2008) and in a cohort of non-RA subjects from the same underlying population. Only patients with no prior history of statin use were included. RESULTS: The study included 161 patients with RA (mean age 56.3 years, 57% female) and 221 non-RA subjects (mean age 56.0 years, 66% female). Prior to the start of statins, the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol were lower in the RA versus the non-RA cohort (P < 0.001 and P = 0.003, respectively). The absolute and percentage change in LDL cholesterol after at least 90 days of statin use tended to be smaller in the RA versus the non-RA cohort (P = 0.03 and P = 0.09, respectively). After at least 90 days of statin use, patients with RA were less likely to achieve therapeutic goals for LDL cholesterol than the non-RA subjects (P = 0.046). Increased erythrocyte sedimentation rate (ESR) at baseline (odds ratio 0.47, 95% confidence interval 0.26-0.85) was associated with lower likelihood of achieving therapeutic LDL goals. CONCLUSION: Patients with RA had lower total cholesterol and LDL cholesterol levels before statin initiation and lower likelihood of achieving therapeutic LDL goals following statin use than the non-RA subjects. Some RA disease characteristics, in particular ESR at baseline, may have an adverse impact on achieving therapeutic LDL goals.
25424578 No male predominance in offspring of women with rheumatoid arthritis or systemic lupus ery 2014 Dec To assess the proportion of male versus female offspring of women diagnosed with SLE or RA, disorders in which female predominance is well known and PsA a disease in which female dominance is less established. The study population encompassed all females aged 16-46, who were members of the Maccabi Health Services (MHS) throughout the period of 2000-2011 and had at least one pregnancy. Data were retrieved from the computerized database of MHS, a 2-million enrollee health maintenance organization operating in Israel. The database was also used to collect data on patients with RA, SLE, and PsA. A total of 182,073 women had at least one indication of pregnancy during the study period. Among them, 546, 270, and 170 were diagnosed with RA, SLE, and PsA, respectively. The proportion of live-born males in 380,472 offspring of women free of these diseases was 51.5 % (95 % CI 51.4-51.7 %). The proportion (95 % CIs) of male offspring born to mothers diagnosed with of RA, SLE, and PsA were 46.3 % (42.3-50.3 %), 51.8 % (46.6-57.0 %), and 50.6 % (42.8-58.5 %), respectively. Our findings support the primary contribution of the hormonal phenotype rather than the genetic phenotype on autoimmunity. Neither patients with SLE or RA differ from the general population by the sex of their offspring.
24034776 Piloting an outpatient policy for funding drugs and their administration in rheumatology. 2013 To ensure appropriate use of outpatient clinic resources, an inter-professional group drafted a policy for an equitable, consistent process requiring the use of patients' drug insurance. The authors' organization remains the payer of last resort. A pilot tested and further informed this policy by targeting rituximab in rheumatoid arthritis. Staff were in-serviced, resources were arranged and patients were informed. Thirty-nine pilot patients (87%) had drug insurance, resulting in a savings of $304,700. Fifty-one hospital infusions were administered in private clinics, avoiding $19,125 in clinic costs. Patient and staff/stakeholder satisfaction surveys provided valuable feedback. Lessons learned will be applied to the policy and related processes in preparation for an organizational-wide implementation.
23295158 Ultrasound examination of symptomatic ankles in shorter-duration rheumatoid arthritis pati 2013 Mar OBJECTIVES: This study investigated the frequency and characteristics of various pathologies in symptomatic ankles in RA patients, especially early RA patients, using power Doppler ultrasound (PDUS). METHODS: We analysed consecutive records of 100 ankles in 74 RA patients who had PDUS scans of symptomatic ankles in our department. The association between US findings and disease duration was analysed. RESULTS: Joint synovitis of ankles including in talocrural, subtalar and talonavicular joints was detected in 56 ankles. Ankle tenosynovitis was detected at the medial recess in 46 ankles, at the lateral recess in 29 ankles, and at anterior aspects in 10 ankles (in 61 ankles overall). Achilles tendon involvement including retrocalcaneal bursitis, Achilles tendon enthesitis, tendonitis, and paratendonitis was detected in 39 ankles. Disease duration was significantly shorter in the ankles with tenosynovitis than in those without tenosynovitis (11.4±21.6 vs. 32.0±58.3 months, p=0.039). Disease duration was even more significantly shorter in ankles with isolated tenosynovitis (i.e., ankles with tenosynovitis but without joint synovitis, n=30) than in all other ankles (5.9±8.7 vs. 25.2±47.8 months, p=0.0016). Tenosynovitis and isolated tenosynovitis, especially, were significantly more common in early RA ankles (disease duration <6 months) than in those with established RA (p=0.0357 and p=0.0236, respectively). CONCLUSIONS: Tenosynovitis and especially isolated tenosynovitis are frequently detected by US in symptomatic ankles of early RA patients. US examination of ankles in early RA patients should include scans of the medial and lateral recess to enable early detection of ankle tenosynovitis.
25401232 Differences in fluorodeoxyglucose positron emission tomography/computed tomography finding 2015 Jul OBJECTIVES: To compare the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) findings in patients with elderly-onset rheumatoid arthritis (EORA) with those in patients with polymyalgia rheumatica (PMR), two conditions with similar clinical presentations. METHODS: We retrospectively analyzed the FDG-PET/CT findings in 10 patients with EORA and 27 patients with PMR admitted to our department between 2006 and 2012. RESULTS: No significant difference was observed in the median patient ages at the time of FDG-PET/CT scans in the EORA and PMR groups (73.5 vs. 78.0 years, respectively). Significant differences in both FDG uptake scores and standardized uptake values were observed between the two groups in the ischial tuberosities, spinous processes, and wrists. No significant differences were detected in the shoulders and hips. However, specific uptake patterns were observed in each group: circular and linear uptake patterns were observed around the humeral head in the EORA group, whereas focal and non-linear uptake patterns were observed in the PMR group. Moreover, focal uptake in front of the hip joint, indicating iliopectineal bursitis, tended to be limited to the PMR group. High sensitivity (92.6%) and specificity (90%) were observed for PMR diagnoses when at least three of the following five items were satisfied: characteristic findings of shoulder and iliopectineal bursitis, FDG uptake in ischial tuberosities and spinal spinous processes, and lack of FDG uptake in the wrists. CONCLUSION: The differences in the degree of uptake at each lesion and in uptake patterns at the shoulders and hips are potentially useful for obtaining a definitive diagnosis.
24178955 Carrier-linked mutual prodrugs of biphenylacetic acid as a promising alternative to biopre 2014 Aug Novel mutual prodrugs of biphenylacetic acid were designed as a promising gastro-protective alternative to fenbufen. Biphenyacetic acid was covalently linked with two non-essential amino acids (D-phenylalanine and glycine) possessing wound healing, analgesic, and anti-inflammatory properties. The prodrugs exhibited good stability in stomach homogenates while hydrolytic release of biphenylacetic acid was observed in phosphate buffer, small intestinal homogenates, and 80% human plasma. In vivo behavior of prodrugs on oral administration to Wistar rats demonstrated 33-45% release of biphenylacetic acid in blood over a period of 24 h indicating passage of intact prodrugs to colon, colonic release of parent drug followed by its absorption through colonic mucosa into systemic circulation. Prodrugs were extensively evaluated for analgesic, anti-inflammatory, anti-arthritic, and ulcerogenic activities. Biochemical, haemetological, histopathological, and radiological studies were also performed. Conversion of bioprecusor fenbufen into mutual carrier-linked prodrugs proved to be promising alternative in terms of reduced ulcerogenic propensity, longer duration of analgesia, enhanced/prolonged anti-inflammatory activity, and superior anti-arthritic effect. These prodrugs could be developed further for chronotherapy of rheumatoid arthritis.
24779919 Genetic variant in IL33 is associated with susceptibility to rheumatoid arthritis. 2014 Apr 29 INTRODUCTION: Interleukin (IL)-33 is a proinflammatory cytokine contributing to the pathogenesis of rheumatoid arthritis (RA). The gene encoding IL-33 may serve as a genetic factor and be associated with the risk of RA. To investigate the potential association between IL33 and RA, we performed a case-control study based on Chinese Han population. METHODS: A three-stage case-control study was performed. Two tag single-nucleotide polymorphisms (SNPs) (rs7044343 and rs10975514), mapping to the IL33 gene, were first genotyped in the discovery population. We further genotyped rs7044343 and rs10975514 in the validation and replication population. The associations between the two tag SNPs and phenotypic subgroups of RA and levels of serum IL-33 were assessed with a logistic regression model. RESULTS: In the discovery population, the CC genotype of rs7044343 was associated with RA patients (odds ratio (OR) = 0.777, 95% confidence interval (CI), 0.611 to 0.988; P = 0.040). After anti-citrullinated peptide antibody (ACPA) stratification, the CC genotype of rs7044343 was also shown to be a protective genotype in RA without ACPA (OR = 0.610; 95% CI, 0.379 to 0.982; P = 0.042). In the validation population and replication population, the association between rs7044343 and RA, especially ACPA-negative RA, was still significant. A meta-analysis of discovery, validation, and replication panels confirmed the association between CC genotype of rs7044343 and RA (Pcombined = 0.0004; ORcombined = 0.77; 95% CI, 0.67 to 0.89). No evidence was found for heterogeneity between three sample sets (Phet = 0.99; I² = 0%). Similar results were also obtained in ACPA-negative RA (Pcombined = 0.0002; ORcombined = 0.57; 95% CI, 0.43 to 0.77). No association was detected between rs10975514 polymorphism and RA susceptibility in the discovery and validation population. The serum levels of IL-33 were significantly lower in the patients with the rs7044343 CC genotype. CONCLUSION: The CC genotype of rs7044343 in IL33 is associated with RA patients and downregulates IL-33 expression in RA.
23136242 Long-term safety of rituximab in rheumatoid arthritis: 9.5-year follow-up of the global cl 2013 Sep 1 OBJECTIVES: Evaluation of long-term safety of rituximab in rheumatoid arthritis (RA). METHODS: Pooled observed case analysis of data from patients with moderate-to-severe, active RA treated with rituximab in a global clinical trial programme. RESULTS: As of September 2010, 3194 patients had received up to 17 rituximab courses over 9.5 years (11 962 patient-years). Of these, 627 had >5 years' follow-up (4418 patient-years). A pooled placebo population (n=818) (placebo+methotrexate (MTX)) was also analysed. Serious adverse event and infection rates generally remained stable over time and multiple courses. The overall serious infection event (SIE) rate was 3.94/100 patient-years (3.26/100 patient-years in patients observed for >5 years) and was comparable with placebo+MTX (3.79/100 patient-years). Serious opportunistic infections were rare. Overall, 22.4% (n=717) of rituximab-treated patients developed low immunoglobulin (Ig)M and 3.5% (n=112) low IgG levels for ≥4 months after ≥1 course. SIE rates were similar before and during/after development of low Ig levels; however, in patients with low IgG, rates were higher than in patients who never developed low IgG. Rates of myocardial infarction and stroke were consistent with rates in the general RA population. No increased risk of malignancy over time was observed. CONCLUSIONS: This analysis demonstrates that rituximab remains generally well tolerated over time and multiple courses, with a safety profile consistent with published data and clinical trial experience. Overall, the findings indicate that there was no evidence of an increased safety risk or increased reporting rates of any types of adverse events with prolonged exposure to rituximab during the 9.5 years of observation.
24551955 [Treatment of tuberculosis in patients with comorbidities]. 2013 Dec Early detection and appropriate treatment are the keys to tuberculosis control. In particular, providing appropriate treatment for tuberculosis in patients with HIV infection, rheumatoid arthritis (RA), chronic hepatic disease, or renal failure necessitating hemodialysis, and taking appropriate measures against adverse reactions to antituberculosis drugs are issues of critical importance. This mini-symposium, four experts explained the current status of "treatment of tuberculosis in patients with comorbidities" and proposed measures to address these problems. Dr. Aoki talked about "HIV infection complicated by tuberculosis." To the next, Dr. Yoshinaga gave a talk on "treatment of tuberculosis in RA patients receiving biological agents. Further, Dr. Sasaki lectured on "tuberculosis in patients with hepatic disease/impairment". Lastly, Dr. Takamori gave a lecture on "tuberculosis in patients with renal disease and those on hemodialysis. Tuberculosis patients often have some underlying diseases, and adverse reactions caused by antituberculosis drugs, such as hepatic and renal impairments, are matters of concern. I believe that this mini-symposium has provided useful information for physicians engaged in tuberculosis treatment and for many other healthcare professionals as well.
23704133 Development of a pharmacodynamic assay based on PLCγ2 phosphorylation for quantifying spl 2013 Sep Spleen tyrosine kinase (SYK) and Bruton's tyrosine kinase (BTK) are key mediators in coupling cell surface receptors, such as the B-cell receptor (BCR), to downstream signaling events affecting diverse biological functions. There is therefore tremendous interest in the development of pharmacological inhibitors targeting the SYK-BTK axis for the treatment of inflammatory disorders and hematological malignancies. A good pharmacodynamic (PD) assay, ideally a blood-based assay that measures proximal events, is warranted for evaluation of such inhibitors. In platelets, collagen-induced activation of membrane glycoprotein GPVI is dependent on the SYK-BTK axis. Here, we report the development of a novel immunoassay that uses the dissociation-enhanced lanthanide fluorescent immunoassay (DELFIA) to measure GPVI-mediated phosphorylation of phospholipase C γ2 (PLCγ2), a direct substrate of SYK and BTK, in platelets. The assay was validated using SYK or BTK inhibitors and generated IC50 correlated with those from the BCR-induced B-cell activation assay. Furthermore, this assay showed good stability and uniformity over a period of 24 h in different donors. Interestingly, compound IC50 values using blood from patients with rheumatoid arthritis were slightly higher compared with those produced using samples from healthy donors. This novel platelet PLCγ2 phosphorylation-based immunoassay should serve as a promising PD assay for preclinical and clinical development of inhibitors targeting the SYK-BTK axis.
26054442 [Safe use of biological therapies for the treatment of rheumatoid arthritis and spondyloar 2015 May The treatment of autoimmune rheumatic diseases has gradually improved over the last half century, which has been expanded with the contribution of biological therapies or immunobiopharmaceuticals. However, we must be alert to the possibilities of undesirable effects from the use of this class of medications. The Brazilian Society of Rheumatology (Sociedade Brasileira de Reumatologia/SBR) produced a document based on a comprehensive literature review on the safety aspects of this class of drugs, specifically with regard to the treatment of rheumatoid arthritis (RA) and spondyloarthritides. The themes selected by the participating experts, on which considerations have been established as the safe use of biological drugs, were: occurrence of infections (bacterial, viral, tuberculosis), infusion reactions, hematological, neurological, gastrointestinal and cardiovascular reactions, neoplastic events (solid tumors and hematologic neoplasms), immunogenicity, other occurrences and vaccine response. For didactic reasons, we opted by elaborating a summary of safety assessment in accordance with the previous themes, by drug class/mechanism of action (tumor necrosis factor antagonists, T-cell co-stimulation blockers, B-cell depletors and interleukin-6 receptor blockers). Separately, general considerations on safety in the use of biologicals in pregnancy and lactation were proposed. This review seeks to provide a broad and balanced update of that clinical and experimental experience pooled over the last two decades of use of immunobiological drugs for RA and spondyloarthritides treatment.
24470496 Phosphoinositide 3-kinase δ regulates migration and invasion of synoviocytes in rheumatoi 2014 Mar 1 Cartilage destruction mediated by invasive fibroblast-like synoviocytes (FLS) plays a central role in pathogenesis of rheumatoid arthritis (RA). Increased cell migration and degradation of extracellular matrix are fundamental to these processes. The class I PI3Ks control cell survival, proliferation, and migration, which might be involved in cartilage damage in RA. PI3Kδ isoform was recently identified as a key regulator of FLS growth and survival, suggesting that it could contribute to synoviocyte aggressive behavior. Therefore, we assessed the role of PI3Kδ in RA synoviocyte migration and invasion. We observed that PI3Kδ inhibition or small interfering RNA knockdown decreased platelet-derived growth factor (PDGF)-mediated migration and invasion of FLS. We then showed that PI3Kδ regulates the organization of actin cytoskeleton and lamellipodium formation during PDGF stimulation. To gain insight into molecular mechanisms, we examined the effect of PI3Kδ inhibition on Rac1/PAK, FAK, and JNK activation. Our studies suggest that Rac1/PAK is key target of PDGF-mediated PI3Kδ signaling, whereas FAK and JNK are not involved. Thus, PI3Kδ contributes to multiple aspects of the pathogenic FLS behavior in RA. These observations, together with previous findings that PI3Kδ regulates FLS growth and survival, suggest that PI3Kδ inhibition could be chondroprotective in RA by modulating synoviocyte growth, migration, and invasion.
22999908 Acute hepatitis E during biotherapy. 2013 Jan Hepatitis E is a rare and usually asymptomatic infection. However, its incidence is rising in France, and it can cause severe or chronic manifestations in immunocompromised patients. Here, we report a case of hepatitis E in a patient with rheumatoid arthritis who had immunosuppression due to treatment with a biological agent.