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ID PMID Title PublicationDate abstract
25440158 The durability of abatacept as a first and subsequent biologic and improvement in HAQ from 2015 Apr OBJECTIVES: Assessment of the effectiveness of newer biologics such as abatacept is essential in real-world practice. METHODS: RA patients administered infusions of abatacept via the Orencia Response Program network with at least one follow-up evaluation were included. The number needed to treat (NNT) to improve HAQ by at least the minimal clinically important difference (MID ≥ 0.22) and abatacept survival and differences between biologic-naïve and TNFi-experienced patients were assessed. RESULTS: Among 2929 patients enrolled, 1771 (60.5%) were eligible for analysis (mean age was 57.6 years, disease duration was 16.5 ± 11.0 (SD) years, 77.2% were female, and 79.2% had past TNFi), with mean follow-up of 13.8 ± 12.3 (SD) months. Half had comorbidities including hypertension (17%), diabetes (8.4%), asthma (6.0%), hypothyroidism (5.7%), and hyperlipidemia (4.0%). Mean (SE) durability of treatment was 26.8 (0.53) months, where 66% were receiving abatacept at 12 months and 53% at 24 months. Patient survival was longer where abatacept was the first biologic vs. post-TNFi (P = 0.0001). In the use of abatacept as a first biologic, 70% achieved MID in HAQ vs. 71% if post-TNFi (P = 0.65) with NNT to improve one patient with at least MID of HAQ was 1.4. CONCLUSIONS: Abatacept is effective in improving HAQ in RA both pre and post first biologic in real-world patients with comorbidities. For those still on abatacept, HAQ continued to improve over the first 2 years. The durability of abatacept is better as a first biologic, but NNT to improve HAQ patients on treatment is the same post-DMARDs and post-TNFi. For treatment durability and HAQ MID achievement, abatacept use as a first biologic is better.
23961668 [Efficacy and adverse reactions of the TNFalpha inhibitor infliximab in rheumatoid arthrit 2013 Jul Abundant evidence of infliximab (tumor necrosis factor inhibitor) has been collected in rheumatoid arthritis. Infliximab is effective not only for resolving the clinical symptoms, but also for preventing joint destruction. It has also been reported that discontinuation of this drug is possible after attaining low disease activity. This is one of the characteristics of infliximab. However, patients should be adequately cautioned against the development of adverse reactions, such as infections. It is essential to carefully select patients eligible for treatment with infliximab based on the guidelines established by the Japan College of Rheumatology, and adverse reactions to the drug should be prevented or detected early and treated promptly.
23996293 Inflammation and hypertension in rheumatoid arthritis. 2013 Nov OBJECTIVE: Hypertension (HTN), a common modifiable cardiovascular risk factor, is more common in patients with rheumatoid arthritis (RA), but the underlying mechanisms are unclear. We examined the hypothesis that mediators of inflammation and markers of cardiovascular risk are associated with HTN in RA. METHODS: We compared measures of inflammation [serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), homocysteine, and leptin concentrations] and insulin resistance [homeostasis model assessment index (HOMA)] in RA patients with (n = 90) and without HTN (n = 79). HTN was defined as blood pressure ≥ 140/90 mm Hg or treatment with antihypertensive therapy. The independent association of markers of interest with HTN was examined using multivariable logistic regression. RESULTS: Patients with HTN were significantly older and had longer disease duration than those without HTN (both p < 0.001). Concentrations of homocysteine [11.1 (8.5-13.5) μmol/l vs 9.3 (7.8-11.0) μmol/l] were significantly higher in patients with HTN (p < 0.001). After adjustment for age, sex, race, smoking, body mass index, and corticosteroid and nonsteroidal antiinflammatory drugs (NSAID) use, increased concentrations of homocysteine (OR 2.9, 95% CI: 1.5-5.5, p = 0.001), and leptin (OR 2.0, 95% CI: 1.0-3.8, p = 0.046) were significantly associated with HTN, but the 28-joint Disease Activity Score, IL-6, CRP, TNF-α, and HOMA index were not (all p > 0.05). CONCLUSION: HTN in patients with RA is not associated with generalized systemic inflammation or insulin resistance, but is associated with increasing concentrations of homocysteine and leptin. The pathogenesis of HTN in RA may involve pathways more regularly associated with fat and vascular homeostasis.
23149217 Nocturnal sleep, daytime sleepiness and fatigue in fibromyalgia patients compared to rheum 2013 Jan OBJECTIVE: Fibromyalgia (FM) and rheumatoid arthritis (RA) are pain disorders, both of which are associated with complaints of sleep disturbance, non-refreshing sleep, and daytime sleepiness and fatigue. Given the putative differential central versus peripheral nervous system involvement in these disorders, subjective and objective measures of nocturnal sleep, daytime sleepiness, fatigue and pain were compared between patient groups and to healthy controls (HC). METHODS: Fifty women (18 with FM, 16 with RA, and 16 HC) completed an 8h nocturnal polysomnogram (NPSG), Multiple Sleep Latency Test (MSLT) the following day, and self-reports of sleepiness, fatigue, and pain. RESULTS: FM and RA patients were similar to each other and had less total sleep time than HC, primarily due to more wake after sleep onset. In an analysis of sleep and wake bouts, both patient groups had longer duration of wake bouts than HC. Nocturnal sleep was judged to be non-restorative for both patient groups. Although reporting the greatest subjective sleepiness and fatigue, FM patients had less objective (MSLT) daytime sleepiness than HC, whereas RA patients were intermediate in objective sleepiness. Unlike the RA and HC, FM patients also showed no association between their subjective and objective sleepiness. CONCLUSIONS: Women with FM have similar nocturnal sleep disturbance as those with RA, but FM patients report greater self-rated daytime sleepiness and fatigue than RA and HC, which did not correspond to the relatively low level of objectively determined daytime sleepiness of FM patients. These findings suggest a generalized hyperarousal state in FM.
25016715 Assessment of ischemia-modified albumin levels in patients with rheumatoid arthritis. 2014 BACKGROUND: Oxygen metabolism has an important role in the pathogenesis of rheumatoid arthritis (RA). Abundant amounts of ROS have been identified in the synovial fluid of RA patients. The accumulation of ROS in cells also serves as an important intracellular signaling of molecules that amplify the synovial inflammatory-proliferative response. Thus, the aim of this study was to assess the IMA levels and other oxidative stress and inflammatory biomarkers in RA subjects. METHODS: IMA, AOPP, CRP, hemoglobin, Hct, MCV, RF, creatinine, urea levels were assessed in 16 RA subjects and 20 healthy controls. RESULTS: IMA levels were significantly higher in the RA group than in the control group (0.495 +/- 0.01 vs. 0.433 +/- 0.02 ABSU, p = 0.038). No significant differences were observed for the other markers studied. CONCLUSIONS: This study demonstrated that RA is related to oxidative stress and inflammation. We also showed for the first time an increase of IMA levels in RA subjects, suggesting that this pathology promotes an increase in the oxidative stress process.
23233309 Association of an activity-enhancing variant of IRAK1 and an MECP2-IRAK1 haplotype with in 2013 Mar OBJECTIVE: To investigate whether a human X chromosome locus of IRAK1 and MECP2 is associated with susceptibility to rheumatoid arthritis (RA), an autoimmune disease that predominantly affects women. METHODS: A total of 2,334 unrelated Korean participants (including 1,318 patients with RA) were genotyped for 5 tag single-nucleotide polymorphisms (SNPs) and 3 additional SNPs in an Xq28 region harboring MECP2 and IRAK1. Twenty-nine additional neighboring SNPs were imputed using the Korean HapMap Project data. All 37 SNPs were statistically tested for association with RA susceptibility, and 2 SNPs associated with RA were examined for their functional effects. RESULTS: RA susceptibility was associated with multiple SNPs in a 79-kb linkage disequilibrium block harboring both MECP2 and IRAK1. The most significant association was for MECP2 SNP rs1734792 (P = 0.00089), but 2 nonsynonymous IRAK1 SNPs, rs1059702 (P = 0.0034) and rs1059703 (P = 0.0042), which were in strong linkage disequilibrium with the MECP2 SNP (D' = 0.87 and 0.91, respectively) affected IRAK1 protein activity. The major haplotype of the 2 nonsynonymous SNPs was associated with a 1.7-fold increase in RA susceptibility versus the minor haplotype (P = 0.0082), and with increased IRAK1 activity, which was demonstrated by a 1.7-fold increase in the intracellular activity of transcription factor NF-κB. CONCLUSION: Our findings indicate that RA susceptibility is associated with multiple SNPs in MECP2 and IRAK1, but high linkage disequilibrium between them does not allow for further localization. Therefore, both genes remain candidates. Nevertheless, the major haplotype of the 2 nonsynonymous IRAK1 SNPs encoding for pPhe196Ser and pSer532Leu confers enhanced IRAK1 activity and, consequently, enhanced susceptibility to RA, as compared to the minor haplotype.
24621448 Bounds on causal interactions for binary outcomes. 2014 Sep A common goal of epidemiologic research is to study how two exposures interact in causing a binary outcome. Causal interaction is defined as the presence of subjects for which the causal effect of one exposure depends on the level of the other exposure. For binary exposures, it has previously been shown that the presence of causal interaction is testable through additive statistical interaction. However, it has also been shown that the magnitude of causal interaction, defined as the proportion of subjects for which there is causal interaction, is generally not identifiable. In this article, we derive bounds on causal interactions, which are applicable to binary outcomes and categorical exposures with arbitrarily many levels. These bounds can be used to assess the magnitude of causal interaction, and serve as an important complement to the statistical test that is frequently employed. The bounds are derived both without and with an assumption about monotone exposure effects. We present an application of the bounds to a study of gene-gene interaction in rheumatoid arthritis.
23316080 Adalimumab, a human anti-TNF monoclonal antibody, outcome study for the prevention of join 2014 Mar OBJECTIVES: To evaluate the efficacy and safety of adalimumab+methotrexate (MTX) in Japanese patients with early rheumatoid arthritis (RA) who had not previously received MTX or biologics. METHODS: This randomised, double-blind, placebo-controlled, multicentre study evaluated adalimumab 40 mg every other week+MTX 6-8 mg every week versus MTX 6-8 mg every week alone for 26 weeks in patients with RA (≤2-year duration). The primary endpoint was inhibition of radiographic progression (change (Δ) from baseline in modified total Sharp score (mTSS)) at week 26. RESULTS: A total of 171 patients received adalimumab+MTX (mean dose, 6.2±0.8 mg/week) and 163 patients received MTX alone (mean dose, 6.6±0.6 mg/week, p<0.001). The mean RA duration was 0.3 years and 315 (94.3%) had high disease activity (DAS28>5.1). Adalimumab+MTX significantly inhibited radiographic progression at week 26 versus MTX alone (ΔmTSS, 1.5±6.1 vs 2.4±3.2, respectively; p<0.001). Significantly more patients in the adalimumab+MTX group (62.0%) did not show radiographic progression (ΔmTSS≤0.5) versus the MTX alone group (35.4%; p<0.001). Patients treated with adalimumab+MTX were significantly more likely to achieve American College of Rheumatology responses and achieve clinical remission, using various definitions, at 26 weeks versus MTX alone. Combination therapy was well tolerated, and no new safety signals were observed. CONCLUSIONS: Adalimumab in combination with low-dose MTX was well tolerated and efficacious in suppressing radiographic progression and improving clinical outcomes in Japanese patients with early RA and high disease activity.
24593201 Remission in patients with active rheumatoid arthritis by tocilizumab treatment in routine 2014 Mar OBJECTIVES: This study aimed to evaluate the remission in rheumatoid arthritis (RA) patients treated with tocilizumab (TCZ), based on prospectively registered data in clinical practice. METHODS: We studied 114 consecutive RA patients treated with TCZ for an average of 3.5 years. Remission was evaluated by using the EULAR criteria and the new ACR/EULAR Boolean-based criteria. RESULTS: Among 114 patients (average age 52.2 years; average disease duration 10.6 years), 76 (67 %) had previously received anti-TNF biologics. Mean baseline DAS28-ESR of 5.4 and improved to 2.4 at 36 months. Overall, DAS28-ESR <2.6 was attained by 66.7 %, while ACR/EULAR remission was attained by 35.1 %. ACR/EULAR remission rate was significantly higher in the patients who were biologics-naïve and had good response at the first month. Among 23 patients who completed the treatment for 3 years and had ACR/EULAR remission at 1 year, 15 (65 %) remained in the remission and 16 (70 %) had a DAS28-ESR <2.6 at the final follow-up. The retention rate at 36 months was 68.2 %. CONCLUSIONS: In patients with RA, TCZ is highly effective for both biologics-naïve patients and patients previously exposed to biologics, achieving a high remission rate and drug continuation rate (68.2 %) in clinical practice.
23515033 [Haematogenous infection of a prosthetic joint]. 2013 Prosthetic joint infection (PJI) is a major complication after total joint arthroplasty. The most common source of these PJIs is a wound infection immediately after implantation of the artificial joint; however, haematogenous infection is also a common source of PJIs. We describe 3 patients, all suffering from (rheumatoid) arthritis, who presented at the emergency department with a wound on the foot or ankle and a swollen and painful prosthetic knee joint, which was functioning well for a long period of time (6 months to 5 years). All patients had several debridements of their infected total knee arthroplasty with local and systemic antibiotics. Patient outcome was widely diverse: from death to successful treatment. These case descriptions are good examples of the different outcomes from a major complication after a small wound. Care should be taken particularly for wounds around the foot and ankle in patients with a total joint arthroplasty, especially those who also have diabetes, rheumatoid arthritis or are immunocompromised.
24323074 Ocular inflammatory diseases associated with rheumatoid arthritis. 2014 Feb The extra-articular complications of rheumatoid arthritis (RA) include ophthalmological manifestations, which can, in some cases, be the first signs of the disease. These inflammatory ophthalmological conditions include episcleritis, scleritis and peripheral ulcerative keratitis (PUK). RA is the leading cause of necrotizing scleritis and of PUK, which are the two most severe ocular conditions associated with the disease. These conditions can rapidly threaten ocular prognosis and are associated with excess mortality in patients with RA owing to their association with systemic vasculitis. Close collaboration between the ophthalmologist and the rheumatologist or internal medicine expert is required for the diagnosis and therapeutic management of these patients. In this Review, we provide an overview of ocular inflammatory diseases in patients with RA with particular focus on the diagnosis and current available therapies (including biologic agents) for these conditions. Furthermore, we propose a decision tree to assist clinicians in their choice of treatment for patients with RA who also have ocular inflammatory disease.
25192300 Infliximab, an anti-TNF-alpha agent, improves left atrial abnormalities in patients with r 2014 Jul BACKGROUND: Rheumatoid arthritis (RA) is associated with increased cardiovascular morbidity and mortality. In the current prospective study, we addressed the impact of RA on left atrial (LA) function and electrical remodelling. Further, we tried to demonstrate the effects of infliximab, an anti-TNF-alpha agent, on echocardiographical LA abnormality in RA patients with preserved left ventricular (LV) ejection fraction. METHODS: We compared 38 female RA patients without clinical evidence of heart disease and 30 female controls without RA and clinical evidence of heart disease. Further, we compared RA patients receiving infliximab and increasing doses of prednisolone over a three-month period. At baseline and post treatment, this study assessed (1) LA and LV parameters using conventional and speckle tracking echocardiography (STE), and (2) electrocardiographic P-wave changes. RESULTS: The values of C-reactive protein (CRP), isovolumic relaxation time (IVRT), A wave, and deceleration time (DT) were significantly higher in RA patients compared to the control group (p < 0.05), whereas E/E' and E/A values were found to be lower (p < 0.05) in RA patients. E/E' values were lower in prednisolone- compared to infliximab-treated patients (p < 0.05). After three months of infliximab and prednisolone treatment, CRP and disease activity score (DAS 28) values decreased in both groups (p < 0.05), and Duke activity status index (DASI) increased (p < 0.05). Maximal left atrial volume index (LAVImax), pre-contraction left atrial volume index (LAVIpreA) and maximum P wave (Pmax) of the RA patients were higher compared to the control group (p < 0.05), whereas LA global strain was found to be lower (p < 0.05). There was no difference in Pmax values between groups before and after the treatment period. E/E', LAVImax and LAVIpreA values of infliximab-treated patients decreased and LA global strain increased after three months of therapy compared to baseline (p < 0.05). At baseline in both treatment groups, E/E' and LA global late diastolic strain rate were lower in prednisolone-compared to infliximab-treated patients (p < 0.05). CONCLUSION: There was echocardiographic LA abnormality in these RA patients. In this patient group there was also a meaningful increase in maximum P wave assessed by electrocardiography. Infliximab therapy for a period of three months improved LA abnormality.
24760484 Traditional Chinese medicine versus western medicine as used in China in the management of 2014 Dec This study is designed to compare the efficacy and safety of traditional Chinese medicine (TCM) with western medicine (WM) in the management of rheumatoid arthritis (RA). This is a 24-week, randomized, multicenter, single-blind study comparing TCM with WM (as used in China) carried out between June 2002 and December 2004 in nine research centers in China, involving 489 patients. Patients were randomized to receive TCM (n = 247), MTX and SSZ (n = 242). MTX was started at a dose of 5 mg to a final dose of 7.5-15 mg weekly. The maintenance dose was 2.5-7.5 mg weekly. The starting dose of SSZ was 0.25 g bid, increasing by 0.25 g a day once a week to a final dose of 0.5-1 g qid. The maintenance dose was 0.5 g tid to qid. Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria (ACR20) at weeks 24. At 24 weeks, ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group, (P < 0.001) at 24 weeks. ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group, (P = 0.01). ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group, (P = 0.14). Side effects were observed more frequently in WM group. In this study, ACR20, ACR50 responses at 24 weeks were significantly better in the WM treated group, by intention to treat (ITT) and per protocol analysis. The ACR 70 response showed no significant difference between the two groups. TCM, while effective in treating RA, appears to be less effective than WM in controlling symptoms, but TCM is associated with fewer side effects.
25152288 [Correlation between synovial TRAF6 expression and serum bone metabolism markers in rheuma 2014 Jun 3 OBJECTIVE: To evaluate the correlation between synovial tumor necrosis factor receptor-associated factor (TRAF) 6 expression and serum bone metabolism markers in rheumatoid arthritis (RA). METHODS: Serum biochemical markers of bone formation (N-terminal propeptide of type I collagen, PINP and N-terminal midfragment of osteocalcin, N-MID.OC) and bone resorption (C-terminal telopeptide of type I collagen, CTX-I) were detected by chemiluminescence in 51 RA patients and 102 age and gender-matched healthy controls from Sun Yat-sen Memorial Hospital during the period of April 2010 to December 2012. Clinical and other serological parameters of reflecting RA activity and severity were collected and correlated with bone metabolism markers. TRAF6 was stained immunohistochemically in synovium from 30 active RA patients and the intensity of TRAF6+ cells was analyzed semiquantitatively. Correlation between synovial TRAF6 expression and serum bone metabolism markers was analyzed. RESULTS: Serum CTX-I level was significantly higher in RA patients than healthy controls ((0.53 ± 0.33) × 10⁻³ vs (0.33 ± 0.16) × 10⁻³ g/L, P < 0.01). Serum PINP and N-MID. OC levels of RA patients were correlated negatively with morning stiffness (P < 0.05), Health Assessment Questionnaire (HAQ) score (P < 0.05) and pain visual analogue scales (VAS) score (P < 0.05). Serum PINP level of RA patients correlated positively with gripping power (r = 0.296, P < 0.05). TRAF6 expression was observed in lining and sublining area of RA synovium and a higher expression of TRAF6 was seen in patients with severe synovitis than those with mild synovitis. Significant correlation was found between synovial TRAF6 expression and serum PINP level (r = 0.381, P < 0.05), as well as serum N-MID.OC level (r = 0.345, P < 0.05). CONCLUSION: Increased bone resorption and altered skeletal bone metabolism are present in RA. An elevated expression of synovial TRAF6 may be correlated with increased compensatory bone formation. And TRAF6 is probably involved in the pathogenesis of bone metabolism imbalance through modulating synovial inflammation in RA.
22842633 MRI characteristics of rheumatoid arthritis in the temporomandibular joint. 2013 OBJECTIVES: The aim of this study was to investigate characteristic MRI findings of rheumatoid arthritis (RA) in the temporomandibular joints (TMJs). METHODS: 61 patients (122 TMJs) with RA in the TMJ and 50 patients (100 TMJs) with temporomandibular disorder (TMD) were included in this study. MR images of these patients were assessed by two oral radiologists for the presence or absence of osseous changes, disc displacement, joint effusion and synovial proliferation. These findings were compared between the two patient groups. RESULTS: Osseous changes in the condyle and articular eminence/fossa in the RA patient group were significantly more frequent than in the TMD patient group, and were often very severe. Joint effusion was also significantly more frequent in the RA patient group. Synovial proliferation was found in all TMJs in the RA patient group, whereas it was very uncommon in the TMD patient group. CONCLUSIONS: Severe osseous changes in the condyle and synovial proliferation were considered characteristic MRI findings of RA in the TMJs.
22090009 Bucillamine-induced yellow nail in Japanese patients with rheumatoid arthritis: two case r 2013 Mar Yellow nail syndrome is an idiopathic condition characterized by a triad consisting of yellow nail, lymphedema, and pulmonary manifestations. Thiol compounds such as D-penicillamine have been reported to be the major cause of drug-induced yellow nail syndrome in patients with rheumatoid arthritis (RA). We recently experienced two Japanese cases with RA who developed yellow nail under treatment with bucillamine, a thiol-containing anti-rheumatic drug developed and approved in Japan. We reviewed the literature for similar cases and identified 36 RA cases with bucillamine-induced yellow nail, mostly in Japanese medical journals. Most of these cases (90.3%) showed improvement of yellow nail after discontinuation of bucillamine, whereas lymphedema and pulmonary manifestations improved only in 30.8 and 35.0% of the patients, respectively.
24263145 Periodontitis and etanercept discontinuation risk in anti-tumor necrosis factor-naive rheu 2013 Dec OBJECTIVE: The objective of this study was to investigate the association between periodontitis (PD) and etanercept (ETN) discontinuation in anti-tumor necrosis factor (anti-TNF)-naive patients with rheumatoid arthritis (RA). METHODS: This retrospective nationwide population-based cohort study identified 3359 anti-TNF-naive patients with RA (age at diagnosis ≥16 years) in whom ETN treatment was initiated using administrative data. We identified PD exposure within 5 years before ETN initiation and during ETN treatment. Cox proportional hazard models were used to assess ETN discontinuation risk associated with PD within 5 years before ETN initiation, shown as hazard ratios with 95% confidence intervals (CIs). Stratified analyses were performed on the basis of PD during ETN treatment to avoid violating the Cox regression assumptions. RESULTS: Patients with PD history during the 5 years before ENT initiation had a higher risk of ETN discontinuation compared with those without such history; the hazard ratios of ETN discontinuation were 1.27 (95% CI, 1.01-1.60) and 1.17 (95% CI, 1.06-1.30) among patients with and without PD during ETN treatment, respectively. Other risk factors included age older than 65 years and daily prednisolone dose greater than 10 mg/d within 1 year before ETN initiation. Concomitant methotrexate, leflunomide, salazopyrin, or hydroxychloroquine administration had a protective effect on ETN discontinuation in patients without PD during ETN treatment, but the protective effect by leflunomide, salazopyrin, and hydroxychloroquine was attenuated in patients with PD during ETN treatment (P for interaction <0.05). CONCLUSIONS: A PD history within 5 years before ETN administration was associated with increased ETN discontinuation risk in anti-TNF-naive patients with RA.
23480185 Protection from articular damage by passive or active anti-tumour necrosis factor (TNF)-α 2013 Apr Active anti-tumour necrosis factor (TNF)-α immunization with the kinoid of TNF-α (TNF-K) induces polyclonal anti-TNF-α antibodies and ameliorates arthritis in human TNF-α (hTNF-α) transgenic mice (TTg). We compared the efficacy of TNF-K to that of infliximab (IFX) and of TNF-K and IFX co-administration, and evaluated whether the titres of anti-hTNF-α antibodies induced by immunization were a determinant of TNF-K efficacy. Forty-eight TTg mice received one of the following treatments: TNF-K immunization (TNF-K group); weekly IFX throughout the study duration (IFXw0-15); TNF-K plus weekly IFX for 4 weeks (TNF-K + IFX); and weekly IFX for 4 weeks (IFXw0-4); PBS. Animals were killed at week 16. Anti-hTNF-α antibody titres and clinical and histological scores were compared. All TNF-K immunized mice (TNF-K and TNF-K + IFX) produced anti-hTNF-α antibodies. Titres were higher in TNF-K versus TNF-K + IFX (P < 0·001) and correlated inversely with histological inflammation (R = -0·78; P = 0·0001) and destruction (R = -0·67; P = 0·001). TNF-K + IFX had higher histological inflammation and destruction versus TNF-K (P < 0·05). A receiver operating characteristic (ROC) analysis of anti-hTNF-α antibody titres identified the criterion cut-off value to discriminate most effectively between the TNF-K and TNF-K + IFX groups. Mice with high versus low titres had less histological inflammation and destruction (P < 0·05). In a model of TNF-α-dependent arthritis, protection from articular damage by TNF-K correlates with the titres of induced anti-hTNF-α antibodies. The co-administration of TNF-K and a short course of infliximab does not result in less articular damage versus solely TNF-K, due probably to lower anti-hTNF-α antibody production. These results are relevant for future development of active anti-TNF-α immunization in human disease.
23249831 Inhibition of high-mobility group box 1 as therapeutic option in autoimmune disease: lesso 2013 Mar PURPOSE OF REVIEW: High-mobility group box 1 (HMGB1) is a molecule that has gained much attention in the last couple of years as an important player in innate immune responses and modulating factor in several (auto)immune diseases. Furthermore, advancements have been made in identifying the diverse functions that HMGB1 can play in the body by studying its receptors, pathways and effects. This review will focus on the modulation of HMGB1 in animal models of (auto)immune diseases. RECENT FINDINGS: In different disease models like sepsis, ischemia-reperfusion and arthritis, HMGB1-blocking therapies have been tested and the disease course was shown to be ameliorated. SUMMARY: These findings indicate that HMGB1 is an important mediator in innate immunity, inflammation and sterile injury. Furthermore, HMGB1 might be a new therapeutic target in inflammation and autoimmune diseases, which may be translated to the clinic.
23873887 Pulmonary involvement in rheumatoid arthritis: multidetector computed tomography findings. 2013 Dec BACKGROUND: Pulmonary involvement in rheumatoid arthritis (RA) is common and encompasses a large spectrum of disease with different treatment options and prognoses. Therefore, assessment of these patients with multidetector computed tomography (MDCT) is vital. PURPOSE: To evaluate the MDCT pulmonary findings of patients with RA and to compare these findings with the clinical status. MATERIAL AND METHODS: Chest MDCT scans of 85 patients with RA between 2006-2012 were assessed. One patient with a pulmonary infection was excluded from the study. MDCT findings and distribution of the CT findings were examined, and patients were classified according to the predominant CT pattern. The pulmonary function test (PFT) results and categories, demographic characteristics, and clinical status of some of the patients for whom the results were obtained were evaluated, and the CT findings, PFT results, demographic characteristics, and clinical status were compared. RESULTS: The study group consisted of 20 men (mean age, 58.1 years ± 13.1; range, 15-77 years) and 64 women (mean age, 55.3 years ± 11.5; range, 30-84 years). The most frequent findings were nodules (78.6%) and pleural thickening (48.8%). The most common CT patterns were follicular bronchiolitis (FB) in 28 (33.3%) patients and nodular disease (ND) in 12 (14.3%) others. There was no statistically significant difference between the CT findings and PFT results, and no statistically significant difference was noted in the CT findings between symptomatic and asymptomatic patients. In addition, there were some patients who exhibited no symptoms and/or had abnormal PFT results but had abnormal CT findings. CONCLUSION: Rheumatoid arthritis is associated with a high frequency of CT findings and CT patterns, with nodules and pleural thickening being the most common CT findings and FB and ND being the most common CT patterns. MDCT identification of patients with RA may be helpful in the evaluation of pulmonary disease, even in patients without symptoms and PFT abnormalities.