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ID PMID Title PublicationDate abstract
23584834 A database for curating the associations between killer cell immunoglobulin-like receptors 2013 The killer cell immunoglobulin-like receptors (KIR) play a fundamental role in the innate immune system, through their interactions with human leucocyte antigen (HLA) molecules, leading to the modulation of activity in natural killer (NK) cells, mainly related to killing pathogen-infected cells. KIR genes are hugely polymorphic both in the number of genes an individual carries and in the number of alleles identified. We have previously developed the Allele Frequency Net Database (AFND, http://www.allelefrequencies.net), which captures worldwide frequencies of alleles, genes and haplotypes for several immune genes, including KIR genes, in healthy populations, covering >4 million individuals. Here, we report the creation of a new database within AFND, named KIR and Diseases Database (KDDB), capturing a large quantity of data derived from publications in which KIR genes, alleles, genotypes and/or haplotypes have been associated with infectious diseases (e.g. hepatitis C, HIV, malaria), autoimmune disorders (e.g. type I diabetes, rheumatoid arthritis), cancer and pregnancy-related complications. KDDB has been created through an extensive manual curation effort, extracting data on more than a thousand KIR-disease records, comprising >50 000 individuals. KDDB thus provides a new community resource for understanding not only how KIR genes are associated with disease, but also, by working in tandem with the large data sets already present in AFND, where particular genes, genotypes or haplotypes are present in worldwide populations or different ethnic groups. We anticipate that KDDB will be an important resource for researchers working in immunogenetics. Database URL: http://www.allelefrequencies.net/diseases/.
24468670 Standardized ethyl acetate fraction from the roots of Brassica rapa attenuates the experim 2014 Apr This study was undertaken to investigate the anti-arthritic potential of a standardized ethyl acetate fraction from the roots of Brassica rapa (EABR) and to explore the molecular mechanisms in adjuvant-induced arthritic rats and macrophages. In AIA-induced arthritic rats, EABR significantly reduced paw swelling, an arthritic index, serum rheumatoid factor, and tissue expression ratio of RANKL/OPG versus vehicle-administered group. This was found to be well correlated with significant suppressions in productions of PGE2, NO, and pro-inflammatory cytokines and in activations of NF-κB in AIA-induced paw tissues and LPS-induced macrophages. EABR attenuated NF-κB activation by reducing the nuclear translocation and phosphorylation of the p65 NF-κB, which were accompanied by parallel reductions in the degradation and phosphorylation of IκBα after blocking the phosphorylation mediated IKK activation. The findings suggest EABR exerts its anti-arthritic and anti-inflammatory properties via NF-κB inactivation in vitro and in vivo, and that EABR is a potential therapeutic for the treatment of arthritis and inflammation-associated disorders.
25354654 Risk factors for fracture among current, persistent users of bisphosphonates. 2015 Feb SUMMARY: Bisphosphonate therapy reduces fracture risk but does not eliminate fracture occurrence. We determined the fracture incidence and risk factors for fractures among 14,674 bisphosphonate users in a community setting. Bisphosphonate users remained at risk of fracture, and additional measures to prevent fractures in these patients would be beneficial. INTRODUCTION: Bisphosphonate therapy reduces but does not eliminate fracture occurrence. The incidence of fracture and risk factors for fractures among persistent, current users of bisphosphonates in a community setting have not been well studied. METHODS: We conducted a retrospective cohort study of 14,674 bisphosphonate users in a health maintenance organization. Patients were followed until a 3-month gap in therapy, creating a pool of highly compliant [mean medication possession ratio (MPR) of 94%] current users. We used Cox proportional hazards models to identify risk factors for fractures among these persistent, current users. RESULTS: There were 867 fractures over the period of observation or 3.7 fractures per 100 users per year. Older patients who take multiple medications, have lower bone mineral density, have a history of prior fracture, and suffer from particular comorbidities (i.e., dementia, chronic kidney disease, and rheumatoid arthritis) are at higher risk of fracture while taking bisphosphonates. CONCLUSION: Persistent, current bisphosphonate users remain at risk of fracture, and additional measures to prevent fractures in these patients would be of benefit.
25300969 Pharmacogenetics of etanercept: role of TNF-α gene polymorphisms in improving its efficac 2014 Dec INTRODUCTION: During the last decade, many new biological immune modulators have entered the market as new therapeutic principles. Biologics, including TNF-α inhibitors, are the new frontier in the treatment of immune-mediated or inflammatory diseases, such as rheumatoid arthritis, systemic lupus erythematosus, Crohn's disease, ankylosing spondylitis, systemic sclerosis, disseminated granuloma annulare, psoriasis and/or psoriatic arthritis. TNF-α inhibitors have demonstrated efficacy and are well tolerated in large, randomized, controlled clinical trials. However, a substantial proportion of patients do not respond to these agents and potential adverse drug reactions may be associated with its use. AREAS COVERED: Pharmacogenetics has the potential of increasing drug efficiency by identifying genetic factors responsible for lack of response or toxicities to TNF-α inhibitors. In this review, we analyze the influence of several polymorphisms upon the efficacy and safety of TNF-α inhibitors. EXPERT OPINION: Several polymorphisms have been proven to influence the response to etanercept. Among them, single nucleotide polymorphisms (SNPs) -308 G/G, -857 C/T, +489 GG and GA, HLA-DRB1-encoding SE (allele *0404 and allele *0101) favor the response to etanercept, whereas SNP -308 A/A and TNFR1A AA decrease the response. Large clinical studies are needed to confirm the relevance of these associations in order to tailor treatment and to decrease unnecessary toxicity.
24807846 Sacroiliac joint involvement in systemic sclerosis. 2015 Jan AIM: One of the major problems for systemic sclerosis (SSc) patients is suggested to be articular involvement. Mostly involved joints in SSc were reported as wrist, carpometacarpal-interphalangeal, foot, knee, hip and shoulder; however, there has been little knowledge on the sacroiliac joint. Our aim was to evaluate sacroiliac joint involvement in SSc. METHODS: Fifty-seven SSc patients, 54 rheumatoid arthritis patients and 64 healthy subjects were included. Anteroposterior pelvic radiographs were obtained and graded twice by three blinded rheumatologists. One competent radiologist has re-evaluated the X-ray results. The ASAS (Assessment of Spondylo Arthritis International Society) scoring method was applied for grading sacroiliac involvement. Inflammatory back pain was also evaluated. Other clinical and laboratory data were collected as proposed by the European Study Group. RESULTS: In the SSc group sacroiliitis was found in 13 patients (23%) and was significantly different from RA patients (two patients, 4%), P = 0.003; and the healthy control group (one participant, 2%), P < 0.001. The frequency of inflammatory back pain in SSc patients with sacroiliitis (8/13 patients, 62%) was significantly higher in SSc patients without sacroiliitis (4/44 patients, 9%), P < 0.001. The SSc patients with sacroiliitis and with inflammatory back pain (8/57 patients, 14%) were regarded as axial spondyloarthritis overlap. Male gender, diffuse subtype, inflammatory back pain and high C-reactive protein levels (odds ratio: 1.069, 1.059, 1.059 and 3.698, respectively) were found to be the significant risk factors for sacroiliitis. CONCLUSION: We suggest that, sacroiliitis may be a concern to be considered in SSc practice.
24819891 Summary health statistics for U.S. adults: national health interview survey, 2012. 2014 Feb OBJECTIVES: This report presents detailed tables from the 2012 National Health Interview Survey (NHIS) for the civilian noninstitutionalized adult population, classified by sex, age, race and Hispanic origin, education, current employment status, family income, poverty status, health insurance coverage, marital status, and place and region of residence. Estimates (frequencies and percentages) are presented for selected chronic conditions and mental health characteristics, functional limitations, health status, health behaviors, health care access and utilization, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age-adjusted and unadjusted versions. DATA SOURCE: NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2012, data were collected on 34,525 adults in the Sample Adult questionnaire. The conditional response rate was 79.7%, and the final response rate was 61.2%. The health information for adults in this report was obtained from one randomly selected adult per family. HIGHLIGHTS: In 2012, 61% of adults aged 18 and over had excellent or very good health. Eleven percent of adults had been told by a doctor or other health professional that they had heart disease, 24% had been told on two or more visits that they had hypertension, 9% had been told that they had diabetes, and 21% had been told that they had some for of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia. Eighteen percent of adults were current smokers and 21% were former smokers. Based on estimates of body mass index, 35% of adults were overweight and 28% were obese.
24576397 Association of painful musculoskeletal conditions and migraine headache with mental and sl 2014 Feb 27 INTRODUCTION: The aim of this study was to determine the prevalence of painful musculoskeletal conditions and migraine headache or any other headache in a sample of Spanish adults with disabilities and their association with anxiety, depression, and sleep disorders. METHODS: This cross-sectional study analyzed data from the Spanish national disability and dependence survey (2007-2008) of 16,932 adults aged 18 or older who have disabilities. The prevalence (95% confidence interval [CI]) of painful musculoskeletal conditions was determined according to a diagnosis of arthritis, osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, muscular dystrophy, and neck or back pain. The prevalence of migraine or other headache was also calculated. Factors associated with these painful conditions were analyzed separately for men and women by using a logistic regression model. RESULTS: The prevalence of painful musculoskeletal conditions was 66.9% (95% CI, 66.2%-67.6%) and that of migraine or other headache was 23.4% (95% CI, 22.8%-24.1%), both of which were higher in women than in men. Factors associated with these conditions in both men and women included older age, a sleep disorder, and concomitant chronic anxiety and/or depression. CONCLUSION: The prevalence of painful musculoskeletal conditions and migraine or other headache is high in people with disability in Spain, especially in women, and these conditions often coexist with depression, anxiety, and/or a sleep disorder. To design programs for rehabilitating and improving the quality of life of adults with disability and painful conditions, treatments for mental and/or sleep disorders should be considered in addition to conventional treatments.
24106233 Cardiac tissue characterization and the diagnostic value of cardiovascular magnetic resona 2014 Jan OBJECTIVE: Accurate diagnosis of cardiovascular involvement in connective tissue diseases (CTDs) remains challenging. We hypothesized that cardiovascular magnetic resonance (CMR) demonstrates cardiac lesions in symptomatic CTD patients with normal echocardiography. METHODS: CMR from 246 CTD patients with typical cardiac symptoms (TCS; n = 146, group A) or atypical cardiac symptoms (ATCS; n = 100, group B) was retrospectively evaluated. Group A included 9 patients with inflammatory myopathy (IM), 35 with sarcoidosis, 30 with systemic sclerosis (SSc), 14 with systemic lupus erythematosus (SLE), 10 with rheumatoid arthritis (RA), and 48 with small vessel vasculitis. Group B included 25 patients with RA, 20 with SLE, 20 with sarcoidosis, 15 with SSc, 10 with IM, and 10 with small vessel vasculitis. CMR was performed by 1.5T; left ventricular ejection fraction, T2 ratio (edema imaging), and late gadolinium enhancement (LGE; fibrosis imaging) were evaluated. Acute and chronic lesions were characterized as LGE positive plus T2 ratio >2 and T2 ratio ≤2, respectively. According to LGE, lesions were characterized as diffuse subendocardial, subepicardial, and subendocardial/transmural due to vasculitis, myocarditis, and myocardial infarction, respectively. A stress study by dobutamine echocardiography or stress, nuclear, or adenosine CMR was performed in CTD patients with negative rest CMR. RESULTS: Abnormal CMR was identified in 32% (27% chronic) and 15% (12% chronic) of patients with TCS and ATCS, respectively. Lesions due to vasculitis, myocarditis, and myocardial infarction were evident in 27.4%, 62.6%, and 9.6% of CTD patients, respectively. Stress studies in CTD patients with negative CMR revealed coronary artery disease in 20%. CONCLUSION: CMR in symptomatic CTD patients with normal echocardiography can assess disease acuity and identify vasculitis, myocarditis, and myocardial infarction.
25488380 Sparing effect of hemiplegia on skin fibrosis and microvascular involvement: reports of tw 2015 Apr OBJECTIVES: The sparing effect of hemiplegia in rheumatic diseases has been described, but reports on systemic sclerosis (SSc)-spectrum disorders are unusual. SSc-spectrum disorders are complex diseases of unknown origin characterized by multisystem involvement, skin and organ fibrosis, microvascular alterations, and immunologic abnormalities. We describe two cases of patients with hemiplegia who developed Raynaud׳s phenomenon and skin fibrosis of the non-paretic limb. METHODS: Clinical, laboratory, and investigation findings of two cases with hemiplegia who developed scleroderma spectrum disorders of the non-paretic limb are presented. A review of the medical literature was performed in PubMed for all articles in English. RESULTS: A total of 46 reports from 1935 to 2012 were identified, especially on osteoarthritis and rheumatoid arthritis. Only two case reports on patients with SSc describe asymmetric SSc skin involvement and unilateral acro-osteolysis on x-ray images of the non-paretic limb. By contrast, we report the first description of capillaroscopic microvascular changes in patients with hemiplegia and asymmetric SSc skin involvement. CONCLUSIONS: Our cases point out the potential role of a "cross-talk" between the nervous system and the skin in SSc-spectrum disorders and suggest future directions for research in studies of pathogenesis.
25036352 Association between IRF5 polymorphisms and autoimmune diseases: a meta-analysis. 2014 Jun 16 In this study, we investigated the association between 5 interferon regulatory factor-5 (IRF5) single nucleotide polymorphisms (SNPs) and autoimmune diseases using the Medline citation index. Twenty-eight studies with 74 comparisons, including 16 rheumatoid arthritis (RA), 43 systemic lupus erythematous (SLE), 2 juvenile idiopathic arthritis (JIA), 6 multiple sclerosis (MS), and 5 systemic sclerosis (SSc) studies, were examined in the meta-analysis. The SNP rs2004640 was significantly associated with SLE, MS, and SSc, but not with JIA [odds ratio (OR)=1.06, 95% confidence interval (CI)=0.90-1.24, P=0.48] or RA (OR=1.03, 95%CI=0.95-1.11, P=0.44). A significant association was observed between rs2280714 and SLE, MS, and SSc, but not RA (OR=1.01, 95%CI=0.94-1.09, P=0.80). Rs10954213 was associated with the pathogenesis of SLE, RA, MS, and SSc. rs2070197 and the exon 6 insertion were significantly associated with SLE. Haplotypes containing rs2004640T and rs2280714T were significantly associated with an increased risk of SLE, but not with RA. This meta-analysis certified that IRF5 polymorphisms confer susceptibility to SLE, MS, and SSc. To further confirm the correlations between polymorphisms of IRF5 and autoimmune disease susceptibility, studies involving a larger number of patients worldwide are necessary.
23602915 Brazilian propolis ameliorates trinitrobenzene sulfonic acid-induced colitis in mice by in 2013 Jun BACKGROUND: Propolis is a resinous substance collected by honeybees from leaf buds and cracks in the bark of various plants. We previously demonstrated the inhibitory activity of Brazilian propolis ethanolic extract against the differentiation process of Th17 cells and pathogenesis of collagen-induced arthritis, which is an experimental animal model of rheumatoid arthritis. Th1 cells are also involved in several autoimmune and inflammatory diseases, such as inflammatory bowel disease. In the present study, we demonstrated for the first time that Brazilian propolis significantly inhibited the generation of Th1 cells. Furthermore, we hypothesized that the administration of propolis to a murine model of colitis would suppress Th1 cell differentiation and ultimately ameliorate colitis. MATERIALS AND METHODS: CD4 T cells were stimulated under Th1-polarizing conditions (immobilized anti-CD3 and anti-CD28 antibodies with IL-12 plus an anti-IL-4 monoclonal antibody for 5days) with or without the propolis ethanolic extract. Cells were characterized for helper T cell subsets by flow cytometric analysis. Furthermore, we investigated the effects of propolis on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis in a mouse model. RESULTS: Propolis dose-dependently reduced the frequency of IFNγ-producing CD4 T cells under Th1-polarizing conditions. Furthermore, the inhibitory effect of propolis on Th1 differentiation was demonstrated in vivo. The severity of colitis in mice fed propolis was significantly lower than that of mice fed the control diet. CONCLUSION: These findings suggest that the suppressive effect of Brazilian propolis on Th1 differentiation may be useful in controlling unbalanced cytokine networks in autoimmune diseases.
23097303 Need for online information and support of patients with systemic sclerosis. 2013 Apr OBJECTIVE: Interactive health communication applications (IHCAs) offer interesting possibilities to support systemic sclerosis (SSc) patients, since SSc is an uncommon, severe disease that needs a multidisciplinary treatment. This study aimed to investigate patients' needs for a hospital-based IHCA. METHODS: A survey study was conducted among a large sample (n = 429) of SSc patients of the University Medical Centre St. Radboud in Nijmegen, The Netherlands. Patients were asked about their current disease-related internet use, their perceived importance of diverse information topics, and their usefulness of 8 widely used online health services. To examine how disease specific their needs were, the results of SSc patients were compared with the results of a sample of rheumatoid arthritis (RA) patients (n = 1,284). RESULTS: In total, 746 patients (44% of the approached patients) returned a completed questionnaire and fulfilled all of the inclusion criteria. Of them, 569 (76%) had internet access. SSc patients used the internet especially for information (85%), and they expressed a need for information on physical, psychological, and social consequences of the disease. Concerning a hospital-based IHCA, e-consults, information about disease and treatment, and home access to their electronic medical records were perceived as most useful. SSc patients were more positive about the usefulness of the online applications than were RA patients, especially for e-consults and peer support forums. CONCLUSION: It would be valuable to offer SSc patients a hospital-based IHCA, including the online information and support they desire. When taking the needs of patients into account, an IHCA could become a valuable addition to their regular treatment.
25004838 Carcinoma cuniculatum in course of etanercept: blocking autoimmunity but propagation of ca 2014 Apr Carcinoma cuniculatum (CC) or verrucous squamous cell carcinoma is a rare variant of squamous cell carcinoma with low incidence of metastasis. It mainly affects men during the fifth-sixth decade of life, arising mostly on the weight-bearing surface of the foot, but it can also be found in other body areas. The favorable effects on the psoriatic, rheumatoid, juvenile polyarthritis as well as the ankylosing spondylitis after the application of Tumour Necrosis Factor (TNF)-alpha inhibitors, like etanercept, presume the availability of similarity between the etiopathogenetic mechanisms which are responsible for the generation of the inflammatory cascade. According to the latest studies, the sensitivity of the patients to TNF-alpha inhibitors could be genetically determined and may also be due to certain genetic polymorphisms of the NLP3 and CARD8 zones of the inflammasome. The blocking of the inflammatory reaction within the borderlines of the psoriatic arthritis could also be accepted as something of a double edged sword. There is a growing volume of literary data which informs us of the clinical manifestation, not only of skin, but also of other types of tumors after the application of TNF-alpha inhibitors. This inevitably generates the hypothesis that within a certain group of patients the TNF-alpha inhibitors have some additional, and currently obscure, effects on presumably key regulatory proteins of the so-called extrinsic apoptotic pathway. Other proteins of the human inflammasome could be also implicated in the regulation of the programmed cell death and the carcinogenesis - there are speculations, that the adapter protein, ASC/TMS1, could be one of these. The present study describes the case of a patient who developed a rare form of skin tumor - epithelioma cuniculatum - whilst undergoing etanercept therapy for psoriatic arthritis. Under discussion are the possible critical connections in the complex regulatory networks of the inflammatory processes, the programmed cell death (apoptosis) and the carcinogenesis which, in the near or distant future, could become the objects of a targeted therapy.
25488989 Ig gene analysis reveals altered selective pressures on Ig-producing cells in parotid glan 2015 Jan 15 In this study, we sought to understand the selective pressures shaping the Ig-producing cell repertoire in the parotid glands of primary Sjögren's syndrome (pSS) patients before and after rituximab treatment (RTX). In particular, we evaluated the role of potential N-glycosylation motifs acquired by somatic hypermutation (ac-Nglycs) within Ig H chain V region (IGHV) genes as alternative selective pressures for B cells in pSS. Five pSS patients received RTX. Sequential parotid salivary gland biopsies were taken before RTX, at 12 wk and at 36-52 wk after treatment. Parotid biopsies from four non-pSS patients served as controls. Sequence analysis was carried out on the IgA and IgG RNA transcripts expressing IGHV3 genes in all parotid biopsies. Both IgG and IgA sequences from pSS patients exhibited no evidence for positive Ag-driven selection pressure in their CDRs in contrast to non-pSS controls. The prevalence of IgG sequences with ac-Nglycs was significantly higher in pSS patients than in non-pSS controls. Selection pressures shaping the IgG and IgA repertoire within pSS patients' parotid glands are distinct from those in non-pSS controls, with very little evidence for positive (auto)antigen selection. The higher prevalence of ac-Nglycs on pSS-IgG compared with non-pSS IgG indicates that ac-Nglycs could be an alternative form of selection pressure. We speculate that B cell hyperproliferation within parotid glands of pSS patients may result from Ag-independent interactions such as that between glycosylated B cell receptors and lectins within the microenvironment rather than (auto)antigen-specific stimulation. Our study brings a new perspective into research on pSS.
25388964 sCD163 in AOSD: a biomarker for macrophage activation related to hyperferritinemia. 2014 Dec Ferritin has a key role in Adult-onset Still's disease (AOSD). Its production seems related to macrophage activation of which sCD163 is a major serum marker. Thus, we aimed at evaluating the role of sCD163 in AOSD and its relationship with ferritin. Furthermore, we determined the expression of CD163 and ferritin in a lymph-node from an AOSD patient. sCD163 and serum ferritin were measured in 34 patients with AOSD (21 active, 13 non-active), 18 sepsis and 22 healthy controls (HC). Immunohistology was performed on a lymph-node from an AOSD patient in order to detect CD163 and ferritin. A tonsil from an HC was used as control. Mean sCD163 (8.6 ± 5.4 mg/L) was higher in active AOSD than "non-active" patients (4.6 ± 2.7 mg/L, p = 0.02). The mean sCD163 in AOSD (6.9 ± 4.9 mg/L) and sepsis (7.1 ± 5.6 mg/L) were higher than in HC (2.56 ± 1.17 mg/L, p < 0.001), but no difference between AOSD and sepsis was detected. sCD163 positively correlated with ferritin (p = 0.0045; r = 0.4755) only in AOSD. Serum ferritin (mean 3,640.1 ± 6,896.9 µg/L) was higher in active AOSD than in sepsis (1,720.2 ± 3,882.1 µg/L, p < 0.007). CD163 was equally distributed in the B and T areas of both lymph-node and tonsil. Differently from the tonsil, ferritin was expressed only in the lymph-node B area. sCD163 is a marker of disease activity in AOSD. The correlation with ferritin may lead to hypothesize a macrophage activation related to hyperferritinemia. Ferritin was found expressed only in the B area of the AOSD lymph-node, suggesting a role for this molecule as an antigen in the disease pathogenesis.
25110401 Drug retention rates and treatment discontinuation among anti-TNF-α agents in psoriatic a 2014 OBJECTIVE: The study aim was to determine treatment persistence rates and to identify causes of discontinuation in psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients in clinical practice. METHODS: Patients treated with adalimumab (ADA), etanercept (ETA), or infliximab (INF) were retrospectively included. Treatment persistence rates were analyzed by means of a stepwise logistic regression. Differences between therapy duration were assessed by means of an analysis of variance model (ANOVA), while a chi-square test was used to evaluate relationships between therapies and causes of treatment discontinuation and the administration of concomitant disease-modifying antirheumatic drugs (DMARDs) among therapies and types of disease considering completed courses of therapy versus courses that were discontinued. RESULTS: 268 patients received a total of 353 anti-TNF treatment courses (97 ADA, 180 ETA, and 76 INF). Comparison among therapies showed significant difference regarding the treatment persistence rates due to the contrast between ETA and INF (P = 0.0062). We observed that 84.7% of patients were still responding after 6 months of follow-up. Comparison among diseases showed that there were significant differences between PsA and AS (P = 0.0073) and PsA and PsA with predominant axial involvement (P = 0.0467) in terms of duration of the therapy, while there were no significant differences with regard to the persistence rate. CONCLUSIONS: In this cohort, anti-TNF-α therapy was associated with high drug persistence rates. As in rheumatoid arthritis, switching to another anti-TNF-α agent can be an effective option when, during the treatment of AS or PsA, therapy is suspended because of inefficacy or an adverse event. Combination therapy with DMARDs was associated with a better persistence rate.
23800367 Peripheral regulatory cells immunophenotyping in primary Sjögren's syndrome: a cross-sect 2013 INTRODUCTION: IL-10-producing B cells, Foxp3-expressing T cells (Tregs) and the IDO-expressing dendritic cells (pDC) are able to modulate inflammatory processes, to induce immunological tolerance and, in turn, to inhibit the pathogenesis of autoimmune disease. The aim of the study was to characterize and to enumerate peripheral IL-10--producing B cells, Tregs and pDCregs in primary Sjögren's Syndrome (pSS) patients in regard of their clinical and serologic activity. METHODS: Fifty pSS patients and 25 healthy individuals were included in the study. CD19⁺-expressing peripheral B lymphocytes were purified by positive selection. CD19⁺/CD24(hi)/CD38(hi)/IL-10-producing B cells, CD4⁺/CD25(hi)/Foxp3⁺ and CD8⁺/CD28⁺/Foxp3⁺ Tregs, as well as CCR6⁺/CD123⁺/IDO⁺ DCs, were quantitated by flow cytometry. RESULTS: Immature/transitional circulating IgA⁺ IL-10-producing B cells had higher levels in pSS patients versus control group, whereas CD19⁺/CD38(hi)/IgG⁺/IL-10⁺ cells had lower percentage versus control. Indeed CD19⁺/CD24(hi)/CD38(hi)/CD5⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD10⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD20⁺/IL-10⁺, CD19⁺/CD24(hi)/CD38(hi)/CD27⁻/IL-10⁺, and CD19⁺/CD24(hi)/CD38(hi)/CXCR7⁺/IL-10⁺ cells had higher frequency in clinical inactive pSS patients when compared with control group. Remarkably, only percentages of CD19⁺/CD24(hi)/CD38(hi)/CD10⁺/IL-10⁺ and CD19⁺/CD24(hi)/CD38(hi)/CD27⁻/IL-10⁺ subsets were increased in pSS serologic inactive versus control group (P < 0.05). The percentage of IDO-expressing pDC cells was higher in pSS patients regardless of their clinical or serologic activity. There were no statistically significant differences in the percentage of CD4⁺/CD25(hi)/Foxp3⁺ Tregs between patient groups versus controls. Nonetheless, a decrease in the frequency of CD8⁺/CD28⁻/Foxp3⁺ Tregs was found in inactive pSS patients versus controls (P < 0.05). CONCLUSIONS: The findings of this exploratory study show that clinical inactive pSS patients have an increased frequency of IL-10--producing B cells and IDO-expressing pDC cells.
23725286 The future of B cell-targeted therapies in Sjögren's syndrome. 2013 Jun Primary Sjögren's syndrome is a systemic autoimmune disease characterized by progressive exocrine gland destruction, resulting clinically in eyes and mouth dryness. To date, no treatment has been proven effective to modify the course of this slow-evolving disease. B cells are now considered to play a central role in the pathogenesis of primary Sjögren's syndrome because their functions are not restrained to antibody production. Thus, several B-cell targeting therapies are under clinical investigation. Rituximab, a monoclonal antibody directed to CD20 and leading to transient blood B-cell depletion, has shown partial improvements in subjective and objective sicca symptoms in small studies. However, the results of two large controlled trials are awaited before considering its use in large populations of patients. Several other therapeutic strategies are being studied, targeting other B-cell surface proteins (epratuzumab and anti-CD22) or major cytokines of B-cell homeostasis (e.g., BAFF, IL-6 and lymphotoxin-β). Although great hope is generated by the trials of these specific therapies, another challenge for clinical researchers is the development of reliable tools to assess the activity of Sjögren's syndrome and its response to treatment.
24447326 High prevalence of Chlamydophila psittaci subclinical infection in Italian patients with S 2014 Jan OBJECTIVES: To assess Chlamydophila psittaci (Cp) subclinical infection in patients with Sjögren's syndrome (SS). METHODS: Seventy-four SS patients (55.4 ±13.4 yrs; 94.6% females) were studied. Among them, 18 had salivary gland mucosa-associated lymphoid tissue (MALT) B-cell lymphoma, 20 myoepithelial sialoadenitis (MESA), and 36 no lymphoproliferative disorders (LPD). The presence of Cp DNA was assessed in peripheral blood of all patients by specific PCR protocols. Paired salivary gland samples were also investigated whenever available (34 cases), including lymphomatous and non-lymphomatous samples, as well as major and minor salivary gland tissues. As controls, 225 blood donors were analysed in the peripheral blood. RESULTS: Overall, Cp DNA was detected in 11/74 (14.9%) SS patients vs. 1/225 (0.4%) controls (p<0.0001). Cp was detected at higher frequency in MALT lymphoma patients (6/18, 33.3%), as compared with MESA (3/20, 15%) or patients without LPD (2/36, 5.6%), (MALT lymphomas vs. others: p=0.02). A similar Cp prevalence was observed in blood vs. salivary gland tissues, however with a higher frequency in the major than in the minor salivary glands (5/18, 27.8%, vs. 1/17, 5.9%, p=0.18). Cp-positive patients were all rheumatoid factor positive (11/11, 100% vs. 40/63, 63.5% Cp-negative; p=0.014), while no difference was noticed for anti-SSA/SSB positivity. CONCLUSIONS: In the light of accepted models of MALT B-cell lymphomagenesis and considering previous data implicating Cp infection in ocular adnexa MALT lymphoma, our results suggest that Cp infection could be involved also in a fraction of patients with SS developing lymphoma. The potential therapeutic implications of these findings appear worthwhile.
24308009 Abnormal nerve conduction study findings indicating the existence of peripheral neuropathy 2013 OBJECTIVE: Chronic inflammatory demyelinating polyneuropathy (CIDP) has been reported in patients with multiple sclerosis (MS). However, there have been limited reports of peripheral neuropathy as a complication of neuromyelitis optica (NMO). In this paper, we showed the characteristics and differences between peripheral neuropathy as a complication of MS and NMO. METHOD: We analyzed a series of 58 MS and 28 NMO patients and evaluated nerve conduction studies (NCS) in 21 MS and 5 NMO patients. RESULTS: Six of the 58 MS and 3 of the 28 NMO patients revealed abnormal NCS findings. Three (5.2%) of the 58 MS patients fulfilled the criteria for CIDP. One (3.6%) of the 28 NMO patients showed peripheral neuropathy at the same time of NMO relapse, although CIDP was not seen in NMO. The other 5 (3 MS and 2 NMO) patients were complicated with neuropathy caused by concomitant diabetes mellitus and Sjögren's syndrome. CONCLUSION: Frequency of abnormal NCS findings might exhibit no significant difference between MS and NMO, although the cause and pathophysiology of peripheral neuropathy were different in MS and in NMO. There might be a group of NMO who were affected simultaneously in the central and peripheral nervous tissues.