Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25440699 [Occupational therapy in rheumatoid arthritis: what rheumatologists need to know?]. 2015 May Interventions focusing on education and self-management of rheumatoid arthritis (RA) by the patient improves adherence and effectiveness of early treatment. The combination of pharmacologic and rehabilitation treatment aims to maximize the possibilities of intervention, delaying the appearance of new symptoms, reducing disability and minimizing sequelae, decreasing the impact of symptoms on patient's functionality. Occupational therapy is a health profession that aims to improve the performance of daily activities by the patient, providing means for the prevention of functional limitations, adaptation to lifestyle changes and maintenance or improvement of psychosocial health. Due to the systemic nature of RA, multidisciplinary follow-up is necessary for the proper management of the impact of the disease on various aspects of life. As a member of the health team, occupational therapists objective to improve and maintaining functional capacity of the patient, preventing the progression of deformities, assisting the process of understanding and coping with the disease and providing means for carrying out the activities required for the engagement of the individual in meaningful occupations, favoring autonomy and independence in self-care activities, employment, educational, social and leisure. The objective of this review is to familiarize the rheumatologist with the tools used for assessment and intervention in occupational therapy, focusing on the application of these principles to the treatment of patients with RA.
24355237 Management of biofilm control in an elderly patient suffering from rheumatoid arthritis: a 2013 Oct The increase in the average age of the population forces dentists and dental hygienists to deal with clinical scenarios typical of the elderly. In old people deep changes present both in systemic and oral health. These changes affect the anatomical and functional integrity of many tissues, such as the mouth. Impairment of patients' oral hygiene becomes manifested by local infections and promotes the pathogenesis of periodontal diseases. There is also a significant increase in autoimmune diseases, which are defined as disorders of the immune system that result in abnormal immune responses. Among the autoimmune diseases of medical interest we report a case of rheumatoid arthritis (RA) strictly related to periodontal disease.
23546972 Comparative genome-wide gene expression analysis of rheumatoid arthritis and osteoarthriti 2013 Mar 11 Both rheumatoid arthritis (RA) and osteoarthritis (OA) are complex diseases. Studies and treatment of RA and OA have mainly focused on individual factors. However, there is still no clear understanding of their causes and adequate treatment alternatives are still being sought. We applied gene set-enrichment analysis to microarray datasets of RA and OA to look for regulatory mechanisms. We found 32 highly significant pathways, including 18 downregulated and 14 upregulated pathways associated with RA. We also identified 18 highly significant pathways, including 7 downregulated and 11 up-regulated pathways associated with OA. Several such pathways were found in both RA and OA, including an upregulated PPAR signaling pathway and downregulated leukocyte transendothelial migration. Regulatory mechanisms in RA seem to be more complex than in OA. This information could be useful for diagnosis and treatment of these two diseases.
24650284 Antidepressant use among persons with recent-onset rheumatoid arthritis: a nationwide regi 2014 OBJECTIVES: The aim of this study was to investigate antidepressant use in a nationwide cohort of persons with incident rheumatoid arthritis (RA) in 2000-2007 in Finland. METHOD: Register data from the Social Insurance Institution of Finland were used to evaluate antidepressant use in ≥ 50-year-old incident RA patients (n = 10,356) and the same-age general population. RESULTS: Of the RA patients, 10.0% (n = 1034) had used antidepressants during the year preceding RA diagnosis. The cumulative incidence of antidepressant initiations after RA diagnosis was 11.4% [95% confidence interval (CI) 10.0-12.9] for men and 16.2% (95% CI 14.9-17.5) for women at the end of follow-up (mean 4.4 years). Female gender [age-adjusted hazard ratio (HR) 1.39, 95% CI 1.21-1.60] and increasing number of comorbidities (p for linearity < 0.001) predicted antidepressant initiations. In the last follow-up year, antidepressant use was at the same level among men with RA [prevalence rate ratio (PRR) 0.93, 95% CI 0.82-1.06] but lower among women (PRR 0.89, 95% CI 0.83-0.95) when compared to the general population. CONCLUSIONS: Antidepressant initiations in early RA were associated with female gender and comorbidity. Although depression is stated to be a sizeable problem in RA, the prevalence of antidepressant use did not exceed the population level.
24718487 Correlation of oxidant status with oxidative tissue damage in patients with rheumatoid art 2014 Nov Rheumatoid arthritis (RA) is a debilitating autoimmune disease whose etiology remains unknown, but studies have consistently implicated a plethora of inflammatory mechanisms culminating in chronic symmetric and erosive synovitis. Importantly, reactive oxygen species (ROS) have been attributed to directly contribute towards the destructive, proliferative synovitis evident in RA. Accordingly, this study aimed to establish whether the degree of oxidative stress and disease activity score (DAS28) correlated with the downstream effects of oxidative damage. The redox status of neutrophils sourced from synovial fluid (SF) was measured by flow cytometry in terms of total ROS and hydroxyl radicals. Among the molecular damage markers, protein carbonylation and lipid peroxidation were detected by spectrophotometry and S-nitrosothiols by fluorimetry. Neutrophils constituted the major cellular component of the SF of patients with RA and their levels of ROS and hydroxyl radicals correlated strongly with protein carbonylation and lipid peroxidation. However, all the oxidative damage markers correlated positively with DAS28. Taken together, in patients with RA, the strong correlation between levels of ROS and DAS28 with markers of oxidative damage suggests that measurement of oxidative stress could serve as a biomarker for monitoring disease severity in RA.
23450275 What's in the black box of arthritis rehabilitation? A comparison of rehabilitation practi 2013 May BACKGROUND: In evaluating complex interventions, it is a challenge for researchers to provide transparent reporting of the intervention content with sufficient detail and clarity such that effects can be compared across studies or countries. OBJECTIVE: To describe and compare the content of current rehabilitation for patients with inflammatory arthritis across 4 northern European countries. PATIENTS AND METHODS: A total of 731 patients with inflammatory rheumatic diseases participated in a multicentre, longitudinal observational study carried out in Sweden, The Netherlands, Denmark and Norway. Data on context, structure and process were reported by patients and teams at the different participating study sites according to the Scandinavian Team Arthritis Register-European Team Intiative for Care Research (STAR-ETIC) framework. RESULTS: Although large similarities were found in the context, there were important differences between the Netherlands and the Scandinavian countries. Regarding structure, there were considerable differences in the length of the rehabilitation period across settings and countries. The most evident differences concerned process variables, especially the type and dosage of individual treatment modalities. CONCLUSION: The variation in important aspects of arthritis rehabilitation found in the present study underline the need for transparent and standardized description of these variables when comparing effects across settings and countries. A standardized description of current practice can be achieved by the STAR-ETIC framework.
24925692 Health Assessment Questionnaire disability progression in early rheumatoid arthritis: syst 2014 Oct OBJECTIVE: The Health Assessment Questionnaire is widely used for patients with inflammatory polyarthritis (IP) and its subset, rheumatoid arthritis (RA). In this study, we evaluated the progression of HAQ scores in RA (i) by systematically reviewing the published literature on the methods used to assess changes in functional disability over time and (ii) to study in detail HAQ progression in two large prospective observational studies from the UK. METHODS: Data from two large inception cohorts, ERAS and NOAR, were studied to determine trajectories of HAQ progression over time by applying latent class growth models (LCGMs) to each dataset separately. Age, sex, baseline DAS28, symptom duration, rheumatoid factor, fulfilment of the 1987 ACR criteria and socio-economic status (SES) were included as potential predictors of HAQ trajectory subgroup membership. RESULTS: The literature search identified 49 studies showing that HAQ progression has mainly been based on average changes in the total study population. In the HAQ progression study, a LCGM with four HAQ trajectory subgroups was selected as providing the best fit in both cohorts. In both the cohorts, older age, female sex, longer symptom duration, fulfilment of the 1987 ACR criteria, higher DAS28 and lower SES were associated with increased likelihood of membership of subgroups with worse HAQ progression. CONCLUSION: Four distinct HAQ trajectory subgroups were derived from the ERAS and NOAR cohorts. The fact that the subgroups identified were nearly identical supports their validity. Identifying distinct groups of patients who are at risk of poor functional outcome may help to target therapy to those who are most likely to benefit.
24219063 The association between serum vitamin D Level and disease activity in Thai rheumatoid arth 2016 Apr BACKGROUND: Serum vitamin D level was inversely associated with the risk of developing new onset rheumatoid arthritis (RA) and disease activity, but some conflicting results have been reported. OBJECTIVE: To examine the serum vitamin D status in Thai RA patients and possible independent factors affecting serum 25 hydroxyvitamin vitamin D (25(OH)D) and the associations of serum 25(OH)D level and the disease activity and functional status in Thai RA patients. METHODS: A cross-sectional study was performed in 239 Thai RA patients. The blood levels of 25(OH)D2 and D3 were measured by chemiluminescent immunoassay. Disease activity was assessed according to tender and swollen joint counts, erythrocyte sedimentation rate (ESR), visual analog scale for global patient assessment, Disease Activity Score-28 (DAS-28) and Thai Health Assessment Questionnaire (Thai HAQ). RESULT: The mean vitamin D level was 28.79 ng/mL. There were no associations between 25(OH)D levels and number of tender and swollen joint counts, DAS-28 score, HAQ score or rheumatoid factor (RF) and/or anti-cyclic citrulinated peptide (CCP) positivity. After multivariated analysis, Bangkok residents, non-farmer, obesity and non-vitamin D supplementation were the predictors for vitamin D insufficiency in Thai patients with RA. CONCLUSION: There are no associations of serum 25(OH)D levels with disease activity or functional status in Thai RA patients. The factors associated with vitamin D insufficiency are Bangkok resident, non-farmer, obesity and not taking vitamin D supplementation.
23725416 Trait emotional intelligence and inflammatory diseases. 2014 Researchers have become increasingly interested in the psychological aspects of inflammatory disorders. Within this line of research, the present study compares the trait emotional intelligence (trait EI) profiles of 827 individuals with various inflammatory conditions (rheumatoid arthritis [RA], ankylosing spondylitis, multiple sclerosis, and RA plus one comorbidity) against 496 healthy controls. Global trait EI scores did not show significant differences between these groups, although some differences were observed when comparisons were carried out against alternative control groups. Significant differences were found on the trait EI factors of Well-being (where the healthy group scored higher than the RA group) and Sociability (where the healthy group scored higher than both the RA group and the RA plus one comorbidity group). The discussion centers on the multifarious links and interplay between emotions and inflammatory conditions.
25128513 Tocilizumab treatment increases left ventricular ejection fraction and decreases left vent 2014 Oct OBJECTIVE: The aim of our pilot study was to prospectively evaluate the effect of inhibiting interleukin 6 on the left ventricular (LV) structure and function in patients with rheumatoid arthritis (RA) without cardiac symptoms, using cardiac magnetic resonance (CMR). METHODS: Female patients with RA with active disease and healthy controls were enrolled. Cardiac symptoms were absent in all subjects. Tocilizumab (TCZ; 8 mg/kg IV every 4 weeks) was prescribed for patients with RA with an inadequate clinical response to methotrexate. All subjects underwent baseline evaluation of LV function and structure measured by CMR. We compared measures of LV geometry and function between patients with RA and patients without RA controls at baseline, and changes in the same variables between baseline and after 52 weeks of treatment among the group with RA. RESULTS: Twenty women with RA were compared with 20 women without RA of similar mean age. In patients with RA at baseline, ejection fraction (EF) was significantly lower (-3.7%) and LV mass index (LVMI) significantly higher (+9.2%) compared with controls. TCZ treatment resulted in a significant decrease in the Simplified Disease Activity Index (SDAI) after 52 weeks of treatment, paralleling a significant increase in EF (+8.2%) and a significant decrease in LVMI (-24.4%) over the same period. The percentage change in LVMI correlated strongly with the percentage change in SDAI (r = -0.63, p = 0.0028). LV geometry in the group with RA at baseline showed eccentric hyper-trophy compared with the group without RA, a condition that normalized after TCZ treatment. CONCLUSION: TCZ treatment significantly increased EF and decreased LVMI associated with disease activity.
23399692 Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis. 2013 Mar Currently, five anti-TNF biologic agents are approved for the treatment of rheumatoid arthritis (RA): adalimumab, infliximab, etanercept, golimumab and certolizumab pegol. Formation of anti-drug antibodies (ADA) has been associated with all five agents. In the case of adalimumab and infliximab, immunogenicity is strongly linked to subtherapeutic serum drug levels and a lack of clinical response, but for the other three agents, data on immunogenicity are scarce, suggesting that further research would be valuable. Low ADA levels might not influence the efficacy of anti-TNF therapy, whereas high ADA levels impair treatment efficacy by considerably reducing unbound drug levels. Immunogenicity is not only an issue in patients treated with anti-TNF biologic agents; the immunogenicity of other therapeutic proteins, such as factor VIII and interferons, is well known and has been investigated for many years. The results of such studies suggest that investigations to determine the optimal treatment regimen (drug dosing, treatment schedule and co-medication) required to minimize the likelihood of ADA formation might be an effective and practical way to deal with the immunogenicity of anti-TNF biologic agents for RA.
24293566 Associations of smoking and alcohol consumption with disease activity and functional statu 2014 Jan OBJECTIVE: To investigate the associations of smoking and alcohol consumption with disease activity and functional status in rheumatoid arthritis (RA). METHODS: We conducted a prospective study consisting of 662 patients with RA who were followed up to 7 years from the Brigham and Women's Hospital Rheumatoid Arthritis Sequential Study. Smoking and alcohol consumption were assessed through yearly questionnaires. The disease activity and functional status were measured annually by the Disease Activity Score examined in 28 commonly affected joints using C-reactive protein (DAS28-CRP3) and the Modified Health Assessment Questionnaire (MHAQ). Linear mixed models were developed to assess the longitudinal effects of smoking and alcohol consumption on DAS28-CRP3 and MHAQ after adjustment for potential confounders. The HLA-DRB1 shared epitope (HLA-SE) by smoking and alcohol interactions were also evaluated in the analysis. RESULTS: The median followup time of the cohort was 4 years. Current smoking was not associated with DAS28-CRP3 in our study, but was associated with a higher MHAQ than nonsmokers with seropositive RA (p = 0.05). Alcohol consumption showed an approximate J-shaped relationship with MHAQ, with the minima occurring at 5.1-10.0 g/day. Compared to no alcohol use, alcohol consumption of 5.1-10.0 g/day was associated with a significant decrease of MHAQ (p = 0.02). When stratified by HLA-SE, the effect of alcohol consumption appeared to be stronger in HLA-SE-positive RA than HLA-SE-negative RA. CONCLUSION: We found that current smoking was associated with a worse functional status, while moderate alcohol consumption was associated with a better functional status in RA. Replications of these findings in other prospective studies are needed.
23092582 The interaction between CXCL10 and cytokines in chronic inflammatory arthritis. 2013 Mar There are several chemokines and their receptors involved in the pathogenesis of chronic inflammatory arthritis. Of those, CXCL10 and its receptor, CXCR3, are increased in many kinds of chronic inflammatory arthritis, especially in rheumatoid arthritis (RA). CXCL10 and CXCR3 play important roles in leukocyte homing to inflamed tissues and in the perpetuation of inflammation, and therefore, tissue damage. In addition to its chemotactic effect, CXCL10 may have pleiotropic functions. Our recent studies show that the crosstalk between CXCL10 and receptor activator of NF-κB ligand (RANKL) in inflamed synovial tissue may induce and perpetuate bone destruction in RA. The interaction between CXCL10 and tumor necrosis factor-α (TNF-α) can also contribute to sustained inflammation in RA. One human trial with anti-CXCL10 monoclonal antibody showed therapeutic potential of blocking CXCL10 in RA treatment. Understanding the novel interaction between this chemokine and other chemokines or cytokines may add possible therapeutic applications in inflammatory arthritis.
23430370 Pulmonary Mycobacterium abscessus disease in a patient receiving low-dose methotrexate for 2013 Dec A 70-year-old woman with methotrexate (MTX)-refractory rheumatoid arthritis (RA) was referred to our hospital for introduction of biological therapy. On high-resolution computed tomography scans, the patient exhibited abnormal findings such as bronchiectasis and centrilobular small nodules, which were highly suggestive of pulmonary nontuberculous mycobacterial (NTM) disease. Although mycobacterial cultures of sputum specimens yielded negative results, cultures of bronchoalveolar lavage fluids grew Mycobacterium abscessus. Frequent follow-up chest radiographs indicated that the patient's pulmonary disease became rapidly worse in 1 month following dose escalation of MTX and administration of low-dose prednisolone. Oral clarithromycin and levofloxacin, chosen on the basis of in vitro susceptibility testing, led to a dramatic recovery from this potentially life-threatening complication. Through our experience with this case, we have learned that (1) pulmonary M. abscessus disease can progress rapidly, even during nonbiological anti-RA therapy; (2) regular follow-up chest radiographs are useful to ensure timely implementation of anti-NTM treatment; (3) bronchoscopic testing should be considered when patients are suspected of pulmonary NTM disease but do not meet the diagnostic criteria; and (4) early isolation, identification, and susceptibility testing of causative NTM species are critical for favorable outcomes.
24286267 Vulnerability to traumatic stress in fibromyalgia patients: 19 month follow-up after the g 2013 Sep 23 INTRODUCTION: The aim of this study was to investigate vulnerability and long-term influence of traumatic stress caused by the Great East Japan Disaster which occurred on March 11, 2011, in patients with fibromyalgia, which is a chronic pain syndrome probably involving central sensitization. METHODS: A total of 60 female patients with fibromyalgia were compared with female patients with rheumatoid arthritis (RA, n = 23) as another chronic pain disease, and with female healthy controls (HC, n = 26) in the observational study. To evaluate responses to traumatic stress, the scores of Impact of Event Scale-Revised (IES-R) were assessed one month after the disaster and every six months until 19 months after the disaster. We also evaluated levels of depression during the study period. To know the score of IES-R of patients with fibromyalgia during usual living, we assessed IES-R in another population of fibromyalgia patients without exposure to a great disaster. RESULTS: The mean score of IES-R one month after the disaster in the fibromyalgia group (24.6 [SD 18.9]) was significantly higher than that of RA group (13.4 [SD 14.5]) or HC group (9.1 [9.2]) (F = 9.96, p < 0.0001). However, the mean score of IES-R in fibromyalgia patients without exposure to a great disaster was (20.3 [SD 18.7]), which was almost the same value as the fibromyalgia group seven months after the disaster (20.2 [SD 19.5]). Repeated measures analysis of variance showed significant effect of time course in the depression-related symptoms (F = 6.68, P = 0.001), and a post-hoc test revealed that the number of depression-related symptoms one month before the disaster was significantly different from other time points until 19 months after the disaster, respectively. CONCLUSIONS: Although response to acute stress induced by the great earthquake was likely to be settled within seven months after the disaster, depression-related symptoms have been increasing for more than one year after the disaster, despite exclusion of patients with major depression at baseline. This long-lasting worsening of depression-related symptoms may have been in response to chronic stress induced by the fear of radiation due to the nuclear power disaster. These findings suggest that patients with fibromyalgia are vulnerable to chronic stress rather than acute stress.
23181974 Utility of combined high-resolution bone SPECT and MRI for the identification of rheumatoi 2013 Feb OBJECTIVES: To evaluate the utility of sequentially acquired, post hoc fused, magnetic resonance imaging (MRI) and multi-pinhole single photon emission computed tomography (MPH-SPECT) with technetium-99m-labeled disphosphonates (Tc99m-DPD) for the identification of finger joints with later erosive progression in early rheumatoid arthritis (ERA) patients. METHODS: Ten consecutive ERA patients prospectively underwent MPH-SPECT and MRI of metacarpophalangeal (MCP) joints prior to and after 6 months methotrexate therapy. Tc99m-DPD uptake was measured at proximal and distal MCP sites using regional analysis. The course of joint pathologies was scored according to the Rheumatoid Arthritis MRI Score (RAMRIS) criteria. RESULTS: The frequency of increased Tc99m-DPD uptake, synovitis and bone marrow edemadecreased under MTX therapy; but the number of bone erosions increased. Joints with progressive and new erosions on follow-up had a higher baseline Tc99m-DPD uptake (2.64 ± 1.23 vs. 1.43 ± 0.91) (p=0.02). CONCLUSIONS: Joints with erosive progression are characterized by an early increased Tc99m-DPD uptake, even in absence of MRI bone pathologies. Tc99m-DPD MPH-SPECT might thus be of additional value to morphological MRI for the identification of RA patients with a high risk for erosive progression.
24901704 Association of cross-reactive antibodies targeting peptidyl-arginine deiminase 3 and 4 wit 2014 BACKGROUND: A subset of rheumatoid arthritis (RA) patients have detectable antibodies directed against the peptidyl-arginine deiminase (PAD) enzyme isoforms 3 and 4. Anti-PAD3/4 cross-reactive antibodies (anti-PAD3/4XR) have been shown to lower the calcium threshold required for PAD4 activation, an effect potentially relevant to the pathogenesis of RA-associated interstitial lung disease (ILD). METHODS: RA patients underwent multi-detector computed tomography (MDCT) of the chest with interpretation by a pulmonary radiologist for ILD features. A semi-quantitative ILD Score (range 0-32) was calculated. Concurrent serum samples were assessed for antibodies against PAD by immunoprecipitation with radiolabeled PAD3 and PAD4. RESULTS: Among the 176 RA patients studied, any ILD was observed in 58 (33%) and anti-PAD3/4XR was detected in 19 (11%). The frequency of any ILD among those with anti-PAD3/4XR was 68% vs. 29% among those with no anti-PAD (crude OR = 5.39; p = 0.002) and vs. 27% among those with anti-PAD4 that was not cross-reactive with PAD3 (crude OR = 5.74; p = 0.001). Both associations were stronger after adjustment for relevant confounders (adjusted ORs = 7.22 and 6.61, respectively; both p-values<0.01). Among ever smokers with anti-PAD3/4XR, the adjusted frequency of any ILD was 93% vs. 17% for never smokers without the antibody (adjusted OR = 61.4; p = 0.001, p-value for the interaction of smoking with anti-PAD3/4XR<0.05). CONCLUSIONS: The prevalence and extent of ILD was markedly higher among RA patients with anti-PAD3/4 cross-reactive antibodies, even after accounting for relevant confounders, particularly among ever smokers. These findings may suggest etiopathologic mechanisms of RA-ILD, and their clinical utility for predicting ILD warrants additional study.
24295447 Synovial membrane immunohistology in early-untreated rheumatoid arthritis reveals high exp 2013 INTRODUCTION: We aimed to investigate the expression and therapeutic modulation of the receptor activator of the NF-κB ligand (RANKL) system in early-untreated rheumatoid arthritis (RA). METHODS: In this study, 15 patients with newly diagnosed RA (median symptom duration 7 months) were started on methotrexate (MTX) 20 mg weekly. Synovial biopsies were obtained by needle arthroscopy at baseline and 8 weeks after initiation of therapy. X-rays of the hands and feet were obtained at baseline and 1 year after diagnosis. Immunohistochemistry was performed to detect RANKL, receptor activator of nuclear factor-κB (RANK) and osteoprotegerin (OPG) in the synovial biopsies. The in vitro effect of MTX was tested on RA-derived primary fibroblasts and the osteoblasts-like osteosarcoma cell line (rtPCR, Western blot and ELISA) and in osteoclasts (tartrate-resistant acid phosphatase staining and dentine pit formation assay). RESULTS: MTX decreased synovial cellularity as well as RANK expression and the RANKL/OPG ratio. We confirmed this effect by a decrease of the mRNA and protein RANKL/OPG ratio in synovial-derived fibroblasts and osteoblasts-like tumoral cells exposed in vitro to methotrexate. Supernatants from MTX treated osteoblasts-like tumoral cells prevented pre-osteoclast formation in the absence of exogenous RANKL. Furthermore, MTX blocked osteoclastogenesis from peripheral blood mononuclear cells despite the presence of macrophage colony stimulating factor and RANKL, which indicates that MTX directly inhibits osteoclastogenesis. CONCLUSIONS: The synovial membrane of early-untreated RA is characterized by a high RANKL/OPG ratio that can be reversed by methotrexate.
24215346 Calpain-1 inhibitors for selective treatment of rheumatoid arthritis: what is the future? 2013 Nov Effective small-molecule treatment of inflammatory diseases remains an unmet need in medicine. Current treatments are either limited in effectiveness or invasive. The latest biologics prevent influx of inflammatory cells to damaged tissue. Calpain-1 is a calcium-activated cysteine protease that plays an important role in neutrophil motility. It is, therefore, a potential target for intervention in inflammatory disease. Many inhibitors of calpains have been developed but most are unselective and so unsuitable for drug use. However, recent series of α-mercaptoacrylate inhibitors target regulatory domains of calpain-1 and are much more specific. These compounds are effective in impairing the cell spreading mechanism of neutrophils in vitro and raise the possibility of treating rheumatoid arthritis with a pill; however, challenges still remain. Improved bioavailability is needed and solution of their precise mode of action should prompt the development of specific calpain-1 screens for novel classes of inhibitors.
23869084 Long-term remission of T-cell large granular lymphocyte leukemia associated with rheumatoi 2013 Aug 29 T-cell large granular lymphocyte leukemia (LGLL) is a rare clonal disease often associated with rheumatoid arthritis (RA) and manifests chiefly as neutropenia and recurrent infections. Immunosuppressive agents are the mainstay of treatment, but long-term remissions are rare. We report 2 cases of LGLL in patients with RA successfully treated with rituximab, a monoclonal antibody specific of B cells and approved for treating RA. The first patient experienced a complete LGLL remission that was sustained during the 8-year follow-up after the first rituximab infusion. In the second patient, rituximab therapy was followed by immediate neutropenia recovery and then by marked shrinkage of the LGLL clone 1 year later. The paradoxical efficacy of this specific anti-B-cell drug on a monoclonal T-cell disease suggests that some cases of LGLL may be reactive manifestations of chronic autoantigen stimulation rather than true malignancies.