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ID PMID Title PublicationDate abstract
25196086 Hydrogen sulfide acts as a pro-inflammatory mediator in rheumatic disease. 2017 Feb OBJECTIVE: Hydrogen sulfide (H(2) S) is a gaseous mediator produced in the body. In experimental models, endogenously produced H(2) S has been shown to have pro-inflammatory effects. The aim of this study was to investigate whether H(2) S is present in three common rheumatic diseases, rheumatoid arthritis (RA), gout and osteoarthritis (OA) and to determine if H(2) S levels correlate with disease activity. METHODS: Patients with RA, gout, OA, and healthy controls (n = 30 each) were recruited. Plasma and where possible, synovial fluid (SF), were obtained. Levels of H(2) S and interleukin-6 (IL-6) (a known inflammatory marker as a positive control) were determined and assessed for their relationship with disease activity. RESULTS: SF-H(2) S levels were significantly elevated in both RA and gout when compared to respective plasma levels. Plasma levels of H(2) S were not different from those in healthy controls in patients with either RA or gout. In OA, plasma levels of H(2) S were significantly elevated compared to healthy controls. In RA, SF-H(2) S levels correlated with Disease Activity Score (DAS)-28 and tender joint count. CONCLUSION: H(2) S is present in the joint and acts as a pro-inflammatory mediator in rheumatic diseases. H(2) S may be a novel therapeutic target for these conditions.
24131486 Induction of proliferation and pro-inflammatory cytokine production in rheumatoid arthriti 2017 Sep OBJECTIVE: To analyze proliferation and pro-inflammatory cytokine production of peripheral blood mononuclear cells (PBMC) from rheumatoid arthritis (RA) patients following stimulation with a purified chondrocyte membrane-associated autoantigen (CH65). METHODS: CH65 was highly purified from bovine chondrocyte membranes by solubilization and ion exchange chromatography. PBMC of RA patients (n = 37; 28 seropositive, nine seronegative) and non-arthritic donors (n = 20) were isolated by ficoll centrifugation and used in cell proliferation assays. The levels of interleukin (IL)-1, tumo necrosis factor (TNF) and IL-6 produced after stimulation with CH65 were determined by enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using Mann-Whitney U-test and Spearman rank test and the software SPSS 13.0(TM) (SPSS Inc.; Chicago, IL, USA). RESULTS: Peripheral blood mononuclear cells exhibited a strong proliferative response to purified CH65 in approximately 50% of the RA patients (seropositive > seronegative), with a maximum reactivity at 0.15 or 0.30 μg/mL culture medium. In contrast, PBMC from normal donors did not show a proliferative response to CH65 at any dose. The proliferative response in RA patients peaked at days 7-9 and returned to control levels at day 13, indicating an antigen-driven process. CH65-stimulated RA PBMC produced moderate to high amounts of IL-1, TNF and IL-6. This was comparable to the response after exposure to isolated whole chondrocyte membranes or purified collagen type II. CONCLUSION: These results demonstrate a significant cellular immune response to CH65 protein in RA patients. Given the high similarity between bovine and human CH65, the results suggest a pathogenetic involvement of this molecule as a cartilage-specific potential target autoantigen in RA.
22772460 Management of rheumatoid arthritis: the 2012 perspective. 2013 Jan Management of rheumatoid arthritis (RA) has improved over the last 10 years. These changes have been monitored in the Institute of Rheumatology, Rheumatoid Arthritis (IORRA) observational cohort, and clinical remission has become a realistic goal. However, we should recognize that the ultimate goal of treatment is to improve long-term outcomes. These improvements have been achieved not only by new drugs, but also by the overall approach toward treating patients. Biologics in RA have been successful; however, safety concerns and pharmacoeconomical issues are still debated. Protein kinase inhibitors have been developed, and can be called "molecular-targeting antirheumatic drugs" (MTARDs), as opposed to "disease-modifying antirheumatic drugs." In comparison with biologics, oral MTARDs should be less expensive; however, their safety profile should be confirmed. Considering the limitations of randomized trials, it is encouraged to conduct studies based on daily practice. It is time to consider the application of the evidence generated from "our" patients to patients in daily practice, namely institute-based medicine as opposed to evidence-based medicine, of which "IORRA-based medicine" would be representative. Finally, there remains much for us rheumatologists to do for our patients, including patient-perspective approaches.
24458537 The effect of disease duration and disease activity on the risk of cardiovascular disease 2015 Jun OBJECTIVE: Disease duration and disease activity may be associated with an increased risk of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The objectives of this study were to investigate (1) the relationship between duration of inflammation and the development of CVD in RA patients and (2) the relationship between RA disease activity over time and CVD in patients with RA. METHODS: RA patients with a follow-up of ≥6 months in the Nijmegen early RA cohort without prior CVD were included. Disease activity over time was calculated using the time-averaged  28 joint disease activity score (DAS28) for each patient. Kaplan-Meier survival analysis and Cox proportional hazards regression were used for the analyses. RESULTS: During follow-up of the 855 patients that were included, 154 CV events occurred. The course of hazards over time did not indicate a change in the risk of CVD over the course of RA (disease duration), which is also reflected by the absence of a deflection in the survival curves. The survival distributions did not differ between patients with a disease duration of <10 years or >10 years (Log-rank test: p=0.82). Time-averaged DAS28 was significantly associated with CVD (p=0.002) after correction for confounders. CONCLUSIONS: Disease duration does not appear to independently affect the risk of CVD. The risk of CVD in RA patients was not increased after 10 years of disease duration compared with the first 10 years. Disease activity over time may contribute to the risk of CVD.
23992260 Safety of infliximab therapy in rheumatoid arthritis patients with previous exposure to he 2013 Aug OBJECTIVE: To evaluate the safety of tumor necrosis factor-α (TNF-α) monoclonal antibody (infliximab) therapy in patients with rheumatoid arthritis (RA) and previous exposure to hepatitis B virus (HBV) who had normal liver function. METHODS: This is a retrospective study from a 26-week, prospective, multicenter trial in 234 patients with RA who received infusions of infliximab (3 mg/kg at week 0, 2, 6, 14 and 22). The medical records of these patients were reviewed, including the information on disease duration, laboratory tests and HBV markers. The data on liver function during the study was analyzed, as well as comparison between patients with previous exposure to HBV and patients without such exposure. RESULTS: Forty-one patients with previous exposure to HBV were HBsAg(-). Forty patients had normal alanine aminotransferase (ALT) and aspartate aminotransferase (AST) and only one patient with positive anti-HBc showed an elevated ALT level before administration of infliximab, and had a further increase of ALT level at week 14, but decreased thereafter. The average ALT and AST levels rose slightly during the treatment but remained in normal range and the differences were insignificant compared with baseline. There was no statistically significant difference in the incidence of liver function abnormalities during the treatment of infliximab between the patients with previous exposure to HBV and those without such exposure. CONCLUSION: In patients with RA and previous exposure to HBV but with a negative HBsAg and normal liver function at baseline, liver function abnormalities were not observed during infliximab treatment.
23911241 Recurrent embolic strokes associated with vertical atlantoaxial subluxation in a patient w 2013 Nov We report a 78-year-old woman with rheumatoid arthritis who developed recurrent embolic cerebellar strokes associated with vertical atlantoaxial subluxation (AAS). On contrast angiography, the bilateral vertebral arteries (VAs) were occluded between the C1 and C2 levels, and the distal parts of bilateral VA were supplied by the collateral circulations. Dynamic cerebral angiography and carotid duplex ultrasonography showed that blood flow was substantially decreased in the left VA and left posterior inferior cerebellar artery on cervical anteflexion. It is suggested that vertical AAS reduced the blood flow of collateral circulation in the left VA with cervical anteflexion and might be a cause of recurrent ischemic stroke.
25320216 Inconsistent treatment with disease-modifying antirheumatic drugs: a longitudinal data ana 2014 Dec OBJECTIVE: Current recommendations advocate treatment with disease-modifying antirheumatic drugs (DMARD) in all patients with active rheumatoid arthritis (RA). We investigated the frequency of and reasons for inconsistent DMARD use among patients in a clinical rheumatology cohort. METHODS: Patients in the Brigham Rheumatoid Arthritis Sequential Study were studied for DMARD use (any or none) at each semiannual study timepoint during the first 2 study years. Inconsistent use was defined as DMARD use at ≤ 40% of study timepoints. Characteristics were compared between inconsistent and consistent users (> 40%), and factors associated with inconsistent DMARD use were determined through multivariate logistic regression. A medical record review was performed to determine the reasons for inconsistent use. RESULTS: Of 848 patients with ≥ 4 out of 5 visits recorded, 55 (6.5%) were inconsistent DMARD users. Higher age, longer disease duration, and rheumatoid factor negativity were statistically significant correlates of inconsistent use in the multivariate analyses. The primary reasons for inconsistent use identified through chart review, allowing for up to 2 co-primary reasons, were inactive disease (n = 28, 50.9%), intolerance to DMARD (n = 18, 32.7%), patient preference (n = 7, 12.7%), comorbidity (n = 6, 10.9%), DMARD not being effective (n = 3, 5.5%), and pregnancy (n = 3, 5.5%). During subsequent followup, 14/45 (31.1%) inconsistent users with sufficient data became consistent users of DMARD. CONCLUSION: A small proportion of patients with RA in a clinical rheumatology cohort were inconsistent DMARD users during the first 2 years of followup. While various patient factors correlate with inconsistent use, many patients re-start DMARD and become consistent users over time.
25205362 Interactions between smoking, increased serum levels of anti-CCP antibodies, rheumatoid fa 2015 OBJECTIVES: To determine to what extent shared epitopes, smoking, and anti-cyclic citrullinated peptide (anti-CCP) antibodies are associated with disease activity and erosive disease in patients with rheumatoid arthritis (RA) at disease onset. METHOD: RA patients not previously treated with disease-modifying anti-rheumatic drugs (DMARDs) and with a disease duration of < 6 months (CIMESTRA study) were examined for shared epitopes, anti-CCP antibodies, immunoglobulin M rheumatoid factor (IgM-RF) and IgA-RF, radiographic erosive changes in hands and feet, and clinical disease activity. RESULTS: The study comprised 153 patients, of whom 104 (68%) were ever-smokers. The prevalence of patients with 0, 1, or 2 shared epitopes was 40 (48%), 71 (49%), and 33 (23%), respectively. Anti-CCP antibodies, IgM-RF, and IgA-RF were present in 89 (58%), 99 (65%), and 82 (54%) patients, respectively. Among smokers, erosive disease was associated with anti-CCP antibodies [odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6-9.3], IgM-RF (OR 4.9, 95% CI 1.9-12), and IgA-RF (OR 2.8, 95% CI 1.2-6.4) but absent with regard to shared epitopes. Among never-smokers, erosive disease was not associated with either shared epitopes or antibodies. All antibody levels measured were associated with smoking and shared epitopes. CONCLUSIONS: Shared epitopes and smoking were associated with the production of anti-CCP antibodies and rheumatoid factors of IgM and IgA isotypes, which again were associated with erosive disease at presentation only in smokers. As shared epitopes and smoking were not directly associated with erosive disease, smoking may enhance the development of erosive disease in RA at different levels or through separate pathways.
23280418 Tumor necrosis factor-inhibiting therapy preferentially targets bone destruction but not s 2013 Mar OBJECTIVE: To investigate how tumor necrosis factor (TNF)-inhibiting therapy affects bone destruction and inflammation in a TNF-driven mouse model of rheumatoid arthritis. METHODS: In order to evaluate the influence of TNF on osteoclastogenesis in vitro, different concentrations of TNF were added to spleen cell-derived monocytes in the absence or presence of different concentrations of RANKL. In addition, the effects of TNF inhibition on osteoclast precursors as well as local bone destruction in vivo were assessed by treating TNF-transgenic mice with different doses of adalimumab. RESULTS: TNF stimulated osteoclastogenesis mainly by increasing the number of osteoclast precursor cells in vitro. This TNF effect was independent of the presence of RANKL. In the hTNF-transgenic mouse model of destructive arthritis, low-dose TNF-inhibiting therapy with adalimumab had no effect on synovial inflammation but significantly inhibited local bone destruction and the generation of osteoclasts. This inhibition was accompanied by a reduction in the number of c-Fms-positive osteoclast precursor cells in the bone marrow and a reduction of the osteoclast precursor pools in the blood and inflamed synovial membrane of hTNF-transgenic mice. CONCLUSION: Low-dose TNF-inhibiting therapy significantly reduces bone erosions by reducing the number of circulating and joint-invading osteoclast precursors. This effect is uncoupled from its antiinflammatory action.
25351754 Cross-cultural adaptation and validation of the Michigan Hand Outcomes Questionnaire (MHQ) 2014 Dec CONTEXT AND OBJECTIVE: Rheumatoid arthritis is a chronic systemic disease that causes joint damage. A variety of methods have been used to evaluate the general health status of these patients but few have specifically evaluated the hands. The objective of this study was to translate, perform cultural adaptation and assess the validity of the Michigan Hand Outcomes Questionnaire for Brazil. DESIGN AND SETTING: Validation study conducted at a university hospital in Curitiba, Brazil. METHODS: Firstly, the questionnaire was translated into Brazilian Portuguese and back-translated into English. The Portuguese version was tested on 30 patients with rheumatoid arthritis and proved to be understandable and culturally adapted. After that, 30 patients with rheumatoid arthritis were evaluated three times. On the first occasion, two evaluators applied the questionnaire to check inter-rater reproducibility. After 15 days, one of the evaluators reassessed the patients to verify intra rater reproducibility. To check the construct validity at the first assessment, one of the evaluators also applied other similar instruments. RESULTS: There were strong inter and intra rater correlations in all the domains of the Michigan Hand Outcomes Questionnaire. Cronbach's alpha was higher than 0.90 for all the domains of the questionnaire, thus indicating excellent internal validity. Almost all domains of the questionnaire presented moderate or strong correlation with other instruments, thereby showing good construct validity. CONCLUSION: The Brazilian Portuguese version of the Michigan Hand Outcomes Questionnaire was translated and culturally adapted successfully, and it showed excellent internal consistency, reproducibility and construct validity.
24123099 Decreased quantity and quality of the periarticular and nonperiarticular bone in patients 2014 Apr Rheumatoid arthritis (RA) is a highly bone destructive disease. Although it is well established that RA leads to bone loss and increased fracture risk, current knowledge on the microstructural changes of bone in RA is still limited. The purpose of this study was to assess the microstructure of periarticular and nonperiarticular bone in female and male RA patients and compare it with respective healthy controls. We performed two high-resolution peripheral quantitative computed tomography (HR-pQCT; Xtreme-CT) scans, one of the distal radius and one of the ultradistal radius in 90 patients with RA (60 females, 30 males) and 70 healthy controls (40 females, 30 males) matched for sex, age, and body mass index. Volumetric bone mineral density (vBMD), bone geometry, and bone microstructure including trabecular bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), cortical thickness (Ct.Th) and cortical porosity (Ct.Po) were assessed. At the distal and ultradistal radius, trabecular (p=0.005 and p<0.001) and cortical BMD (p<0.001 and p<0.001) were significantly decreased in male and female patients with RA, respectively. BV/TV was also decreased at both sites, based on lower Tb.N in female RA (p<0.001 for both sites) and lower Tb.Th (p=0.034 and p=0.005) in male RA patients compared with respective healthy controls. Cortical thinning (p=0.018 and p=0.002) but not Ct.Po (p=0.070 and p=0.275) was pronounced in male and female RA patients at the distal radius. Cortical perimeter was increased in male and female RA patients at both sites. Multiple regression models showed that bone geometry (cortical perimeter) is predominantly influenced by age of the RA patient, cortical thickness by both age and disease duration, and trabecular microstructure predominantly by the disease duration. In summary, these data show profound deterioration of bone microstructure in the appendicular skeleton of RA patients at both periarticular and nonperiarticular sites.
25028787 Anti-C1q in chronic hepatitis C virus genotype IV infection: association with autoimmune r 2015 A growing body of evidence suggests that anti-complement-1q (anti-C1q) antibodies are elevated in a variety of autoimmune disease. Therefore, we investigated their prevalence and clinical significance in plasma of patients with hepatitis C virus (HCV) genotype IV in the presence and absence of autoimmune extra hepatic manifestations in comparison to normal healthy individuals. Plasma Anti-C1q Abs levels were assessed by an Enzyme Linked Immunosorbant Assay in 91 chronic HCV-infected patients (51 with and 40 without autoimmune rheumatic manifestations) and 40 healthy volunteers matched for age and gender. Epidemiological, clinical, immunochemical and virological data were prospectively collected. Positive Anti-C1q antibodies were more frequent among HCV patients with extra-hepatic autoimmune involvement, than those without and healthy control subjects. No significant correlations were found between Anti-C1q levels with either the liver activity or the fibrosis scores. In HCV-patients with autoimmune involvements, plasma Anti-C1q levels were significantly higher in patients with positive cryoglobulin, and in those with lymphoma than in those without. These results were confirmed by multivariate analysis. Further large scale longitudinal studies are required to assess and clarify the significance and the pathogenic role of anti-C1q antibodies among HCV infected patients with positive cryoglobulinaemia and lymphoma.
24261616 Rheumatoid arthritis disease activity and vitamin D deficiency in an Asian resident popula 2016 Apr AIM: We aimed to assess the prevalence of vitamin D deficiency and its association with rheumatoid arthritis (RA) disease activity in a UAE population. METHODS: Forty-five consecutive subjects were prospectively recruited during the early summer with their clinical examination and Health Assessment Questionnaire (HAQ) being recorded at a clinic appointment, along with their blood sample being taken for the 25-hydroxyvitamin D (25(OH)D) total test. RESULTS: Thirty-five (76%) patients claimed to be exposed to sunlight for < 30 min daily. The prevalence of vitamin D insufficiency (20-30 ng/mL) and deficiency (< 20 ng/mL) was 36% and 29%, respectively. RA patients who exposed their hands and feet (29 ng/mL) or more (34 ng/mL) to the sunlight had serum vitamin D levels higher than those who exposed their hands alone (18 ng/mL) or less (19 ng/mL) (P < 0.05). The variations in vitamin D levels due to skin color did not reach significance. No significant correlation was seen between serum vitamin D levels and Disease Activity Score (DAS28) or HAQ scores. A direct relationship was observed between HAQ scores and DAS28 scores (P < 0.05). CONCLUSION: We highlight the importance of skin exposure to sunlight in a conservative dressing culture. No association was observed between vitamin D and disease activity. However, the high prevalence of vitamin D deficiency may negatively impact on bone health of these patients in the future.
23714112 The level of fatty acid-binding protein 4, a novel adipokine, is increased in rheumatoid a 2013 Oct OBJECTIVE: To assess the expression of the novel adipokine Fatty Acid Binding Protein-4 (FABP4) in synovial tissues, serum and the synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and to study the relationships among FABP4, disease activity and metabolic status. METHODS: FABP4 levels were measured in the serum and synovial fluid of 40 patients with RA and 40 control patients with OA. The disease activity score (DAS28), C-reactive protein (CRP) levels and serum lipids were assessed in patients with RA. Immunohistochemical analysis and confocal microscopy were used to study the expression and cell-specific distribution of FABP4 in synovial tissues. RESULTS: The age, sex and body mass index (BMI) adjusted levels of FABP4 were significantly higher in the serum (p=0.001) and synovial fluid (p=0.005) of patients with RA when compared to OA patients. FABP4 levels were higher in females than in males and correlated positively with body mass index (BMI) in patients with RA. Independent of confounders, FABP4 levels correlated with total cholesterol and LDL cholesterol in patients with RA, but not in OA patients. FABP4 levels were not affected by disease activity. Furthermore, the increased expression of FABP4 that was otherwise restricted to synovial fibroblasts, macrophages and B-cells was noted in RA patients at levels higher than that observed in OA patients. CONCLUSIONS: The observed elevation of FABP4 levels in RA patients and the positive correlation of the adipokine to cholesterol suggest that FABP4 may represent a potential link between RA and the increased risk of atherosclerotic changes.
24684878 Targets of immune regeneration in rheumatoid arthritis. 2014 Apr Many of the aging-related morbidities, including cancer, cardiovascular disease, neurodegenerative disease, and infectious susceptibility, are linked to a decline in immune competence with a concomitant rise in proinflammatory immunity, placing the process of immune aging at the center of aging biology. Immune aging affects individuals older than 50 years and is accelerated in patients with the autoimmune disease rheumatoid arthritis. Immune aging results in a marked decline in protective immune responses and a parallel increase in tissue inflammatory responses. By studying immune cells in patients with rheumatoid arthritis, several of the molecular underpinnings of the immune aging process have been delineated, such as the loss of telomeres and inefficiencies in the repair of damaged DNA. Aging T cells display a series of abnormalities, including the unopposed up-regulation of cytoplasmic phosphatases and the loss of glycolytic competence, that alter their response to stimulating signals and undermine their longevity. Understanding the connection between accelerated immune aging and autoimmunity remains an area of active research. With increasing knowledge of the molecular pathways that cause immunosenescence, therapeutic interventions can be designed to slow or halt the seemingly inevitable deterioration of protective immunity with aging.
24584924 Abatacept reduces levels of switched memory B cells, autoantibodies, and immunoglobulins i 2014 Apr OBJECTIVE: Abatacept (ABA) is a chimeric molecule, able to block the CD28-mediated costimulatory pathway. To evaluate the hypothesis that, through this mechanism of action, ABA may down-modulate the immune responses of B lymphocytes in rheumatoid arthritis (RA), we investigated the serum levels of immunoglobulins (Ig), free light chains (FLC), anticitrullinated protein antibodies (ACPA), and rheumatoid factor (RF), as well as the number of B lymphocytes differentiated into post-switch memory cells in patients treated with ABA. METHODS: The serum levels of Ig, FLC, different ACPA, RF isotypes, and the B cell phenotype were longitudinally evaluated in 30 patients with RA treated with ABA. RESULTS: At baseline, the proportion of total and post-switch memory B cells was lower in RA than in healthy individuals. After 6 months of ABA treatment we observed significant reductions of serum levels of IgG, IgA, and IgM, as well as FLC, with a normalization in many patients who had initially abnormal values. A significant reduction of the titers of IgG- and IgA-ACPA, as well as of IgM-, IgA-, and IgG-RF was also observed. A decrease of autoantibodies below the upper limits of normal values was found in 2 of 26 patients (8%) initially seropositive for IgG-ACPA, 1 of 14 (7%) for IgA-ACPA, 5 of 22 (23%) for IgM-RF, 7 of 22 (30%) for IgA-RF, and 5 of 16 (31%) for IgG-RF. After treatment, the proportion of circulating post-switch memory B cells was also further significantly decreased. CONCLUSION: ABA treatment in patients with RA can reduce signs of polyclonal B cell activation, inducing a trend toward normalization of serum levels of different classes of Ig and of FLC, decreasing titers of ACPA and RF, and percentages of post-switch memory B cells.
24977987 Association of dry eye and inflammatory systemic diseases in a tertiary care-based sample. 2014 Aug PURPOSE: The aim of this study was to review the frequency and types of inflammatory systemic diseases in a cohort of patients with dry eye, and identify clinical features suggesting the presence of these. METHODS: Consecutive new patients with a primary diagnosis of dry eye evaluated at a tertiary dry eye center between January 2010 and December 2011 were reviewed retrospectively. Standardized questionnaires were used to obtain data regarding systemic symptoms, previous medical diagnoses, and family history. Dry eye evaluations included Schirmer testing, tear film break-up time, corneal fluorescein staining, and bulbar conjunctival lissamine green staining. Clinically significant dry eye was defined as having a Schirmer test score without anesthesia of ≤10 mm or conjunctival lissamine green staining of ≥1 using the Oxford scale. RESULTS: A total of 228 new patients were analyzed. Of these, 47.4% (108/228) presented with a known diagnosis of inflammatory disease. Based on a review of systems and ocular examination, 81 patients (81/228) underwent a further work-up that revealed 25 additional diagnoses that were not known on presentation. The most common newly identified conditions included occult thyroid eye disease (n = 20), primary Sjögren Syndrome (4), and Sjögren Syndrome suspect (1). Female gender, family history of autoimmune disease, self-reported joint pain or dry mouth, external signs of orbital inflammation, and conjunctival chemosis were more common in patients with inflammatory systemic disease as compared with that in patients with no identifiable condition (P < 0.05 for all). CONCLUSIONS: Systemic inflammatory diseases are frequently associated with dry eye in patients evaluated at a tertiary academic center. Diagnostic evaluations may help uncover previously undiagnosed significant conditions in about one-third of tested patients.
23545897 Genetic variants associated with methotrexate efficacy and toxicity in early rheumatoid ar 2014 Feb Methotrexate (MTX) has emerged as first-line therapy for early moderate-to-severe rheumatoid arthritis (RA), but individual variation in treatment response remains unexplained. We tested the associations between 863 known pharmacogenetic variants and MTX response in 471 Treatment of Early Aggressive Rheumatoid Arthritis Trial participants with early RA. Efficacy and toxicity were modeled using multiple regression, adjusted for demographic and clinical covariates. Penalized regression models were used to test joint associations of markers and/or covariates with the outcomes. The strongest genetic associations with efficacy were in CHST11 (five markers with P<0.003), encoding carbohydrate (chondroitin 4) sulfotransferase 11. Top markers associated with MTX toxicity were in the cytochrome p450 genes CYP20A1 and CYP39A1, solute carrier genes SLC22A2 and SLC7A7, and the mitochondrial aldehyde dehydrogenase gene ALDH2. The selected markers explained a consistently higher proportion of variation in toxicity than efficacy. These findings could inform future development of personalized therapeutic approaches.
25026811 [Subclinical interstitial lung disease associated with rheumatoid arthritis]. 2014 Interstitial lung disease (ILD) in rheumatoid arthritis (RA) is its extra-articular manifestation. At the same time, ILD considerably worsens the prognosis of the disease. Mortality rates for interstitial pulmonary fibrosis are 6% of all-cause mortality in RA patients. ILD can be identified by clinical examination only in 2-6% of cases, by plain chest X-ray in 1-6%, and by high-resolution computed tomography in 50-60%. The paper deals with subclinical ILD and discusses the state-of-the-art of investigations in this area.
25185889 Anti–citrullinated protein antibody positivity correlates with cartilage damage and prot 2014 Dec Objective: To investigate the factors associated with cartilage proteoglycan content in patients with rheumatoid arthritis (RA) Methods: 32 RA patients received high-field 3 Tesla Gadolinium-Enhanced MRI of Cartilage (dGEMRIC) for determining cartilage proteoglycan content. Measurements were performed in three individual cartilage regions (medial, central, lateral) of the metacarpophalangeal joints 2 and 3. dGEMRIC values were then related to disease duration, disease activity, anti-citrullinated protein antibody (ACPA) status, rheumatoid factor status and C-reactive protein level. Results: dGEMRIC values were not significantly different between the MCP2 and MCP3 joint. Inter-class correlations were high (>0.92) for all three (medial, central and lateral) cartilage compartments. dGEMRIC values were significantly lower in RA patients with longer disease duration (≥3 years) and those with ACPA positivity than those with a short disease duration (<3 years)(p=0.034) or negative ACPA (p=0.0002), respectively. In contrast, no association between cartilage proteoglycan content and disease activity, C-reactive protein level and rheumatoid factor status was found. Conclusion: Decreased cartilage proteoglycan content in RA patients is associated with disease duration and ACPA positivity but not with the actual disease activity, CRP level or rheumatoid factor status. These data suggest that the cumulative burden of inflammation as well as ACPA are the determinants for cartilage damage in RA.