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

ID PMID Title PublicationDate abstract
20062996 Etanercept induced organizing pneumonia in a patient with rheumatoid arthritis. 2012 Apr TNF inhibitors are being used in a rapidly expanding number of rheumatoid arthritis (RA) patients due to their effectiveness and acceptable safety profiles. To date, concerns regarding the adverse effects of TNF inhibitors have focused on infections, hematologic malignancies, and demyelinating disorders. Recently, the development of autoantibodies and other autoimmunity has been increasingly reported. Here, we describe a 36-year-old RA patient in whom organizing pneumonia and systemic lupus erythematosus were detected during etanercept treatment.
22985493 Common genetic variants associated with disease from genome-wide association studies are m 2013 Jun WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The link between inflammation and cancer has long been reported and inflammation is thought to play a role in the pathogenesis of many cancers, including prostate cancer (PrCa). Over the last 5 years, genome-wide association studies (GWAS) have reported numerous susceptibility loci that predispose individuals to many different traits. The present study aims to ascertain if there are common genetic risk profiles that might predispose individuals to both PrCa and the autoimmune inflammatory condition, rheumatoid arthritis. These results could have potential public heath impact in terms of screening and chemoprevention. OBJECTIVES: To investigate if potential common pathways exist for the pathogenesis of autoimmune disease and prostate cancer (PrCa). To ascertain if the single nucleotide polymorphisms (SNPs) reported by genome-wide association studies (GWAS) as being associated with susceptibility to PrCa are also associated with susceptibility to the autoimmune disease rheumatoid arthritis (RA). MATERIALS AND METHODS: The original Wellcome Trust Case Control Consortium (WTCCC) UK RA GWAS study was expanded to include a total of 3221 cases and 5272 controls. In all, 37 germline autosomal SNPs at genome-wide significance associated with PrCa risk were identified from a UK/Australian PrCa GWAS. Allele frequencies were compared for these 37 SNPs between RA cases and controls using a chi-squared trend test and corrected for multiple testing (Bonferroni). RESULTS: In all, 33 SNPs were able to be analysed in the RA dataset. Proxies could not be located for the SNPs in 3q26, 5p15 and for two SNPs in 17q12. After applying a Bonferroni correction for the number of SNPs tested, the SNP mapping to CCHCR1 (rs130067) retained statistically significant evidence for association (P = 6 × 10(-4) ; odds ratio [OR] = 1.15, 95% CI: 1.06-1.24); this has also been associated with psoriasis. However, further analyses showed that the association of this allele was due to confounding by RA-associated HLA-DRB1 alleles. CONCLUSIONS: There is currently no evidence that SNPs associated with PrCa at genome-wide significance are associated with the development of RA. Studies like this are important in determining if common genetic risk profiles might predispose individuals to many diseases, which could have implications for public health in terms of screening and chemoprevention.
22841415 A high prevalence of autoimmune indices and disorders in primary nummular headache. 2012 Sep 15 BACKGROUNDS: Nummular headache (NH) is currently considered a form of peripheral neuralgia originating from the terminal branch in epicranial tissue but its etiopathogenesis is still unknown. Since autoimmune disorders often involve the trigeminosensory nerve to provoke craniofacial pain, we hypothesize that autoimmunity aberration may play a role with regard to NH. METHODS: We examined the antibodies to antinuclear factor, ds-DNA, extracted nuclear antigens, rheumatoid factor, as well as antiphospholipid antibodies, in 23 primary NH patients. RESULTS: Among them were 16 patients (69.6%) found as having at least one abnormal autoimmune index, namely, antibodies to antinuclear factor in 8 patients, SSA/La in 6 patients, rheumatoid factor in 4 patients, SSB/Ro in 2 patients, and ds-DNA in 1 patient. An abnormal increase of blood anti-beta2-glycoprotein I antibody was noted in 4 patients and lupus anticoagulant in 1 patient, whereas HLA-B27 seropositivity was detected in 1 patient. Except for 2 patients positive for antinuclear factor without other associated features, 15 patients (65%) were finally diagnosed as having Sjogren/sicca syndrome, rheumatoid arthritis or antiphospholipid antibody syndrome. CONCLUSIONS: A high prevalence of abnormal autoimmune indices and disorders is present in primary NH patients, suggesting a probable relationship between autoimmunity aberration and epicranial neuralgia in NH.
22958181 Associations of systemic diseases, smoking and contact lens wear with severity of dry eye. 2012 Nov PURPOSE: Systemic diseases, smoking, ocular surgeries and contact lens wear have been linked with dry eye but it is not known if these factors are also associated with severity of dry eye. A cross-sectional investigation was conducted on the effect of various systemic and ocular conditions with respect to the severity of dry eye in Asian patients. METHODS: Prospective recruitment of consecutive new referral patients from a dry eye clinic was performed. Medical history, dry eye symptoms and clinical assessment were coded in a standardised form and analysed. RESULTS: Out of 510 patients (25% men), mean ± S.D. age 53.0 ± 14.1 years, 25 had previous diagnosis of rheumatoid arthritis, 30 had diabetic mellitus, 41 had thyroid disease, and 33 were current smokers; 23 and 41 patients had previous LASIK and cataract surgery respectively and 90 were current contact lenses wearers. A previous diagnosis of rheumatoid arthritis was associated with more severe superior corneal fluorescein staining (OR = 11.2, 95% CI 4.6-27.4). CONCLUSION: Generally, with the exception of rheumatoid arthritis, there were no associations between dry eye severity and systemic diseases, smoking, previous ocular surgeries and contact lens wear. Dry eye patients with rheumatoid arthritis tend to have more severe ocular surface damage in the superior cornea.
20570193 Does rain really cause pain? A systematic review of the associations between weather facto 2011 Jan OBJECTIVE: To examine the association between weather and pain in rheumatoid arthritis (RA). METHODS: Systematic review of longitudinal observational studies (up to September 2009) with data on the association between weather variables and severity of pain in RA. The methodological quality was rated independently by the two authors according to an adapted Newcastle-Ottawa Scale. We analyzed the data on an aggregated (group) level with a meta-analysis of correlations between pain and weather, and at an individual level as the proportion of patients for whom pain was significantly affected by the weather. RESULTS: Nine studies were included. Many different weather variables have been studied, but only three (temperature, relative humidity and atmospheric pressure) have been studied extensively. Overall group level analyses show that associations between pain and these three variables are close to zero. Individual analyses from two studies indicate that pain reporting in a minority (<25%) of RA patients is influenced by temperature, relative humidity or atmospheric pressure. We were not able to relate the findings to methodological quality or other aspects of the studies. CONCLUSION: The studies to date do not show any consistent group effect of weather conditions on pain in people with RA. There is, however, evidence suggesting that pain in some individuals is more affected by the weather than in others, and that patients react in different ways to the weather. Thus, the hypothesis that weather changes might significantly influence pain reporting in clinical care and research in some patients with RA cannot be rejected.
22303622 Loneliness in patients with rheumatic diseases: the significance of invalidation and lack 2012 Jan Rheumatic diseases affect about 20% of the population, leading to common symptoms such as joint problems, pain, fatigue, and stiffness. Loneliness is prevalent in individuals with rheumatic diseases. This could be due to not receiving social support and being stigmatized and invalidated, which might be most common in fibromyalgia, a rheumatic disease that lacks medical evidence. The aim of this study was to compare loneliness in distinct rheumatic diseases and to examine the association of loneliness with social support and invalidation. Participants were 927 patients with ankylosing spondylitis (n = 152), fibromyalgia (n = 341), osteoarthritis (n = 150), rheumatoid arthritis (n = 171), or systemic diseases (n = 113). They completed online questionnaires including an 11-point Likert scale assessing loneliness, the Illness Invalidation Inventory (3*1; Kool et al., 2010), and the Social Support Survey (SSS; De Boer, Wijker, Speelman, & De Haes, 1996; Sherbourne & Stewart, 1991). Patients with fibromyalgia experienced significantly more loneliness than patients with ankylosing spondylitis and patients with rheumatoid arthritis. Besides being younger, having lower education, and not working, in multiple regression analyses both lack of social support and invalidation were independently correlated with loneliness. This suggests that to decrease loneliness, therapeutic attention should be given to both increasing social support as well as decreasing invalidation in patients with rheumatic diseases, especially in patients with fibromyalgia.
22838733 Monocyte populations as markers of response to adalimumab plus MTX in rheumatoid arthritis 2012 Jul 27 INTRODUCTION: The treatment of rheumatoid arthritis (RA) patients with anti-tumor necrosis factor alpha (TNFα) biological drugs has dramatically improved the prognosis of these patients. However, a third of the treated patients do not respond to this therapy. Thus, the search for biomarkers of clinical response to these agents is currently highly active. Our aim is to analyze the number and distribution of circulating monocytes, and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16+ subsets in methotrexate (MTX) non-responder patients with RA, and to determine their value in predicting the clinical response to adalimumab plus MTX treatment. METHODS: This prospective work investigated the number of circulating monocytes, and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets, in 35 MTX non-responder patients with RA before and after three and six months of anti-TNFα treatment using multiparametric flow cytometry. The number of circulating monocytes in an age- and sex-matched healthy population was monitored as a control. RESULTS: Non-responder patients with RA show an increased number of monocytes and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets after three months of adalimumab plus MTX treatment that remained significantly increased at six months. In contrast, significant normalization of the numbers of circulating monocytes was found in responders at three months of adalimumab plus MTX treatment that lasts up to six months. CX3CR1 expression is increased in monocytes in non-responders. At three months of anti-TNFα treatment the number of circulating monocytes and their subsets was associated with at least 80% sensitivity, 84% specificity and an 86% positive predictive value (PPV) in terms of discriminating between eventual early responders and non-responders. CONCLUSIONS: The absolute number of circulating monocytes and of their CD14⁺highCD16⁻, CD14⁺highCD16⁺ and CD14⁺lowCD16⁺ subsets at three months of adalimumab plus MTX treatment, have a predictive value (with high specificity and sensitivity) in terms of the clinical response after six months of anti-TNFα treatment in patients with RA.
22846615 Drug-specific Th2 cells and IgE antibodies in a patient with anaphylaxis to rituximab. 2012 Rituximab (RTX) is currently used in the treatment of lymphoproliferative diseases and of several rheumatologic disorders and is a frequent cause of acute infusion reactions, usually classified as cytokine release syndrome (CRS). Some infusion reactions to RTX raise concern for immediate type I hypersensitivity, even if to date RTX-specific IgE antibodies have not been reported. To improve knowledge of the mechanisms of reactions to RTX, we investigated humoral and cellular immune responses to this drug in a patient suffering from rheumatoid arthritis who displayed two immediate infusion-related reactions. RTX-exposed tolerant patients and healthy untreated subjects were used as controls. Non-isotype-specific and IgE anti-RTX antibodies were positive in the serum samples collected from the reactive patient but not in those from the control groups. Only the reactive patient also displayed skin testing positivity with RTX. More importantly, RTX-stimulated peripheral blood mononuclear cells from the reactive patient, but not from the controls, displayed a dose-dependent proliferative response associated with a Th2 cytokine production profile. Our results show the presence of RTX-specific Th2-type cells and IgE antibodies, thus suggesting that type I hypersensitivity may be an additional mechanism to CRS in the development of RTX reactions.
23138557 [Glycosylation-dependent effector function of IgG antibodies]. 2012 Nov The Fc fragments of pathogenic IgG autoantibodies in patients with rheumatoid arthritis are low-galactosylated and low-sialylated. In contrast, high-galactosylated and high-sialylated antigen-specific IgG antibodies are sufficient to inhibit a pro-inflammatory immune response in an antigen-specific manner and might be a promising therapeutic tool to re-establish tolerance against defined self-antigens in autoimmune patients.
21220089 Herbal medicine in the treatment of rheumatic diseases. 2011 Feb Herbal medicines are popular, self-prescribed treatments for rheumatic conditions. A recent US survey suggested that approximately 90% of arthritic patients use alternative therapies such as herbal medicines. This article provides a brief overview of the evidence on herbal medicines for 4 common rheumatic conditions: back pain, fibromyalgia, osteoarthritis, and rheumatoid arthritis.
21724701 CCL20 stimulates proinflammatory mediator synthesis in human fibroblast-like synoviocytes 2011 Sep OBJECTIVE: To compare levels of the chemokine CCL20 and its receptor CCR6 in donor, osteoarthritic (OA), and rheumatoid arthritis (RA) synovium; and to determine the molecular mechanism of cellular activation induced by chemokine/receptor ligation in human fibroblast-like synoviocytes (FLS). METHODS: Synovia and isolated FLS from donor, OA, and RA joints were analyzed for CCL20 and CCR6 expression by RT-PCR and immunohistochemistry. The effect of CCL20 on cytokines and mediators of cartilage degradation was examined by PCR for mRNA expression levels and ELISA, and Western blotting for protein. CCL20-dependent transcriptional and posttranscriptional activation of target genes was monitored using reporter constructs and luciferase assays in transfected donor FLS. RESULTS: CCL20 and CCR6 proteins were abundantly expressed in RA synovial lining cells compared to donor or OA synovia as judged by immunohistochemistry. RT-PCR of synovial extracts confirmed the predominance of CCL20/CCR6 mRNA expression in RA synovium. CCL20 mRNA expression was low in donor FLS, but increased dramatically after stimulation with recombinant human (rh) interleukin 1ß (IL-1ß). rhCCL20 increased mRNA and protein expression of COX-2, IL-1ß, tumor necrosis factor-α, IL-6, and the matrix-destructive metalloprotease MMP-3 in donor FLS cultures. High constitutive levels of IL-6 were released from RA synovia; CCL20-induced expression of IL-6 occurred through an NSAID/COXIB-sensitive process. CCL20-induced expression of COX-2 was mediated by a PLCP1/PKCα/MEK1/2/ERK1/2-dependent pathway involving both transcriptional and posttranscriptional mechanisms. CONCLUSION: CCL20/CCR6 may play an important role in the pathogenesis of RA by assembling the molecular and cellular components orchestrating synovitis.
23255648 Total wrist arthroplasty using the Universal 2 prosthesis. 2012 Dec PURPOSE: To report outcomes of 21 total wrist arthroplasties (TWA) using the Universal 2 prosthesis. METHODS: Five men and 14 women aged 44 to 82 (mean, 62) years underwent 21 total wrist arthroplasties for rheumatoid arthritis (n=19) and post-traumatic arthritis (n=2) by a single surgeon using the Universal 2 prosthesis. Pre- and post-operative pain and function were assessed by a single surgeon using the Disabilities of the Arm, Shoulder and Hand (DASH) score and the patient-rated wrist evaluation (PRWE) score. Range of motion, stability, dislocation rate, and neurovascular status were also assessed. Radiographs were evaluated for implant alignment and fit, screw positioning, and implant loosening. RESULTS: The mean time to assessment of the range of motion was 3.1 (range, 1.8-3.9) years, and the mean time to assessment of the PRWE score was 4.8 (range, 2.1-7.3) years. The range of motion in each direction and the mean DASH and PRWE scores improved significantly following TWA. Two patients had restricted range of motion, which was treated by manipulation under anaesthetic (after 6 months in one and 8 weeks in the other). One patient underwent excision of a palmar bony bridge. One patient endured extensor pollicis longus rupture and underwent tendon transfer after 5 months. Radiographs revealed no evidence of implant loosening, migration, or malalignment. There was no sign of osteonecrosis in the remaining carpals or metacarpals. CONCLUSION: The Universal 2 TWA achieved significant improvement in range of motion and functional outcome of the wrist, with reduced rates of early joint instability, dislocation, and implant loosening, compared to previous implants. The small implant size and cementless design reduce bone loss and osteonecrosis.
22271229 Access to the next wave of biologic therapies (Abatacept and Tocilizumab) for the treatmen 2012 Jun Patients in England and Wales with rheumatoid arthritis (RA) receive treatment from the National Health Service (NHS) with therapies approved by the European Medicines Agency (EMA), under guidance from the National Institute for Health and Clinical Excellence (NICE). This document overviews the current NICE guidelines for the treatment of RA and identifies scenarios when such guidance may not represent the optimum management strategy for individual patients. Specifically, we consider the use of tocilizumab or abatacept as the most appropriate treatments for some patients. In such scenarios, it may be possible for the clinician to secure access to the required therapy through an application procedure known as an 'individual funding request', the process of which is described in detail here. At present, it is unclear the extent to which the proposed reform of the NHS will affect the role of NICE in providing guidance and setting standards of care. Until the full impact of the proposed changes are realized, individual funding requests will remain a valuable way of securing the optimal treatment for all patients suffering from RA.
23070535 Hemorrhagic-acquired factor XIII deficiency associated with tocilizumab for treatment of r 2012 Dec Factor XIII (FXIII) is the final enzyme in the coagulation cascade. Acquired FXIII deficiency is caused by inhibitors of FXIII or decreased synthesis and/or increased consumption of FXIII, which leads to severe bleeding. Recently, we experienced a case of hemorrhagic-acquired factor XIII deficiency that occurred during treatment with the IL-6 inhibitor tocilizumab for rheumatoid arthritis. A 48-year-old man was referred because of right hip pain due to a hematoma. Laboratory findings showed that routine coagulation tests were normal, while FXIII activity was slightly low (52.4 %). The patient was successfully treated with plasma-derived factor XIII concentrates. The time course of recovery suggests that tocilizumab might have inhibited FXIII production. To our knowledge, this is the first report of acquired factor XIII deficiency associated with administering of tocilizumab. When recurrent bleeding is seen during administering of tocilizumab, acquired factor XIII deficiency may have been induced, thus attending physicians should consider this disease in a differential diagnosis.
22453529 Preliminary report on a study of health-related quality of life in patients with rheumatoi 2013 Feb There are studies about health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA), but few studies prospectively assessed HRQoL. The main purpose of this study was to analyze HRQoL in patients hospitalized due to RA exacerbation and observed over a planned 2-year follow-up in an outpatient setting. The study involved 42 women and 9 men, at mean age of 62.5 years (SD ± 12.6). The mean duration of the study was 22-23 months. The HRQoL analysis was performed using the SF-36 survey. At the beginning of the study, basic data on age, sex, selected biochemical (ESR, CRP, GFR, hemoglobin, plasma albumin, plasma protein), and clinical parameters (the duration of RA, VAS, DAS28, BMI, the presence of cardiovascular disease, diabetes, osteoporosis, osteoporotic fractures, osteoarthritis, neoplasm) were collected. Questionnaires were completed at the beginning and end of the study. Statistically significant reductions in HRQoL scores were observed in social functioning (SF; 0.42 vs 0.32, P < 0.05), whereas role-emotional health (RE; 0.48 vs 0.59, P < 0.05) and mental health (MH; 0.47 vs 0.54, P < 0.05) scores were increased. A decrease in the SF was positively correlated with the lack of osteoporosis at baseline (r = 0.35, P > 0.02). An increase in the MH was inversely correlated with BMI (r = -0.31, P < 0.05), and the level of hemoglobin (r = -0.32, P < 0.028) and positively correlated with the presence of osteoarthritis at baseline (r = 0.29, P < 0.05). In RA patients, dimensions of HRQoL as SF, RE, and MH could change within 2 years and these changes could be related to comorbidities. Although preliminary findings are promising, further studies are needed.
22084093 Glucocorticoid therapy of antigen-induced arthritis depends on the dimerized glucocorticoi 2011 Nov 29 Despite several side effects, glucocorticoids (GCs) have been widely used for 60 y to treat rheumatoid arthritis on the basis of their antiinflammatory effects. However, the cells targeted by GCs and the transcriptional mechanisms underlying their actions through the glucocorticoid receptor (GR) in steroid therapy remain poorly defined. Using cell type-specific GR-deficient mice subjected to antigen-induced arthritis (AIA) as a model of human rheumatoid arthritis, we show that GC action on T cells but not myeloid cells is critical for therapeutic intervention in AIA. Furthermore, the resistance of mice expressing a DNA binding-defective GR (GR(dim)) to GC treatment reveals that dimerization of the GR is indispensable for the antiinflammatory effects. In these mice, the GC-induced suppression of T(H)1 and T(H)17 cell-derived proinflammatory cytokines is impaired. Our finding that IL-17A(-/-) mice are resistant to GC therapy, whereas IFN-γ(-/-) mice respond as efficiently as WT mice implies that IL-17-producing T cells and not IFN-γ-producing T cells are the most important targets for an efficient GC therapy. The present study's identification of the critical cell type and the mode of GR action in steroid therapy of AIA significantly advances our understanding of steroid therapy and should lead to therapies with greater efficiency and fewer side effects.
22923182 Subsequent entry biologics/biosimilars: a viewpoint from Canada. 2012 Sep We have reviewed the issues surrounding the advent of biosimilars in the rheumatoid arthritis biologic field. Our proposals emphasize the need to focus primarily on patient safety and to assess the outcomes of therapy both in the short and longer term.
21941174 Certolizumab pegol therapy for rheumatoid arthritis-associated scleritis. 2012 Jan PURPOSE: To report the successful treatment of rheumatoid arthritis (RA)-associated scleritis with the tumor necrosis factor alpha antagonist certolizumab pegol. METHODS: Retrospective case report of therapeutic interventions for a 47-year-old woman with scleritis and RA. After not tolerating treatment with other tumor necrosis factor alpha inhibitors and rituximab, or after that treatment failed, certolizumab pegol was administered in an attempt to achieve better control of her disease process. RESULTS: Six months after beginning the new therapy, it was well-tolerated and the patient's RA and scleritis were quiescent. CONCLUSIONS: Certolizumab pegol may successfully treat RA-associated scleritis, even in a patient who has not tolerated therapy with other tumor necrosis factor alpha antagonists or in whom that treatment has failed.
21787418 Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and h 2011 Jul 25 INTRODUCTION: To examine the effects of tumour necrosis factor (TNF) blocking therapy on the levels of early mitochondrial genome alterations and oxidative stress. METHODS: Eighteen inflammatory arthritis patients underwent synovial tissue oxygen (tpO(2)) measurements and clinical assessment of disease activity (DAS28-CRP) at baseline (T0) and three months (T3) after starting biologic therapy. Synovial tissue lipid peroxidation (4-HNE), T and B cell specific markers and synovial vascular endothelial growth factor (VEGF) were quantified by immunohistochemistry. Synovial levels of random mitochondrial DNA (mtDNA) mutations were assessed using Random Mutation Capture (RMC) assay. RESULTS: 4-HNE levels pre/post anti TNF-α therapy were inversely correlated with in vivo tpO(2) (P < 0.008; r = -0.60). Biologic therapy responders showed a significantly reduced 4-HNE expression (P < 0.05). High 4-HNE expression correlated with high DAS28-CRP (P = 0.02; r = 0.53), tender joint count for 28 joints (TJC-28) (P = 0.03; r = 0.49), swollen joint count for 28 joints (SJC-28) (P = 0.03; r = 0.50) and visual analogue scale (VAS) (P = 0.04; r = 0.48). Strong positive association was found between the number of 4-HNE positive cells and CD4+ cells (P = 0.04; r = 0.60), CD8+ cells (P = 0.001; r = 0.70), CD20+ cells (P = 0.04; r = 0.68), CD68+ cells (P = 0.04; r = 0.47) and synovial VEGF expression (P = 0.01; r = 063). In patients whose in vivo tpO(2) levels improved post treatment, significant reduction in mtDNA mutations and DAS28-CRP was observed (P < 0.05). In contrast in those patients whose tpO2 levels remained the same or reduced at T3, no significant changes for mtDNA mutations and DAS28-CRP were found. CONCLUSIONS: High levels of synovial oxidative stress and mitochondrial mutation burden are strongly associated with low in vivo oxygen tension and synovial inflammation. Furthermore these significant mitochondrial genome alterations are rescued following successful anti TNF-α treatment.
22933072 A murine autoimmune model of rheumatoid arthritis and systemic lupus erythematosus associa 2012 T-helper cell 17 (Th17) cells play an important role in the pathogenesis of many autoimmune disorders including Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). In this chapter we describe a murine model where deregulated production of IL-17 and IL-21 can lead to either lupus-like disease or RA-like symptoms depending on the genetic background. We delineate the key techniques that can be used to dissect the mechanisms responsible for the pathogenesis of these diseases at both a cellular and molecular level including in vitro Th17 cell differentiation, chromatin immunoprecipitation assays, and retroviral transduction experiments. We also describe the methodologies that can be utilized to monitor the classic clinical findings of RA and SLE in murine models. Given the broad involvement of deregulated production of IL-17 and IL-21 in autoimmunity, many of these techniques could also be valuable for the investigation of these pathways in murine models of other autoimmune diseases.