Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
---|---|---|---|---|
26106442 | Life events, emotional responsiveness, and the functional prognosis of patients with rheum | 2015 | BACKGROUND: Stressors may differently affect human physiological systems according to the host properties relevant to psycho-behavioral processes that the stressors invoke. In a Japanese multicenter cohort study of patients with rheumatoid arthritis (RA), we examined if major life events differently contribute to the patients' functional prognosis according to their ability to identify emotions as manifest feelings when encountering the events (emotional responsiveness). METHODS: 460 patients with RA completed a self-administered baseline questionnaire about psychosocial factors including emotional responsiveness. Two years later, they checked on a list of positive/negative personal events that happened during the two-year study period. Rheumatologists evaluated their functional status at baseline and follow-up using the ACR classification system. RESULTS: In a multiple logistic regression model that included baseline demographic, disease activity/severity-related, therapeutic, and socioeconomic factors as covariates, none of the counts of positive, negative, or all life events was associated with the functional status at follow-up. In the subgroup with poor emotional responsiveness, however, these life event counts were all associated with a poorer functional prognosis (odds ratio of ACR class 3-4 vs. 1-2 associated with one increment in the all life-event count = 2.39, 95 % confidence interval = 1.27-4.48, p = .007), while no such relationship was evident for the rest of the patients. CONCLUSIONS: Major life events, whether positive or negative in nature, may have an impact on the disease course of patients with RA when the patient has poor emotional responsiveness to the event(s). | |
26002456 | Imaging Methods of Joint Damage in Early Rheumatoid Arthritis. | 2015 | Rheumatoid arthritis (RA) is an autoimmune connective tissue disease of unknown etiology with development of persistent and erosive arthritis ultimately resulting in disability. The prevalence of RA is about 0.5-1% in adults worldwide. Radiographic changes in the joints at early stages of the disease are often absent. Accordingly, there is a need for instrumental methods of diagnosis with greater sensitivity. These include magnetic resonance imaging and ultrasound of joints. The paper reviews the instrumental methods of diagnosis of joint damage in early RA according to the existing literature of PubMed database. Selection criteria were original articles in the English language reporting «X-ray», «MRI» and «ultrasound» in patients with early RA. | |
26210125 | New Classification Criteria for Systemic Sclerosis (Scleroderma). | 2015 Aug | The American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria for the classification of systemic sclerosis (SSc) were developed to classify more patients with SSc for studies and improve on previous criteria. The new classification criteria have the following criteria: skin thickening of the fingers extending proximal to the metacarpophalangeal joints. Seven additive items are each given a numerical weight: skin thickening, fingertip lesions, telangiectasia, abnormal nail fold capillaries, lung involvement, Raynaud's phenomenon, and SSc-related autoantibodies. The ACR/EULAR classification criteria for SSc have good sensitivity and specificity but do not substitute for diagnostic criteria. | |
27022536 | EVALUATION OF THE CERVICAL SPINE AMONG PATIENTS WITH RHEUMATOID ARTHRITIS. | 2010 Mar | OBJECTIVE: To evaluate the prevalence of cervical spine abnormalities among patients with rheumatoid arthritis and correlate the imaging findings with the clinical state. METHODS: A cross-sectional study on 35 patients was carried out at the School of Medicine of the Federal University of Goiás (UFG) in 2004. The following were evaluated: age, use of medications and the clinical picture of pain and neurological characteristics. The erythrocyte sedimentation rate (ESR) and rheumatoid factor were tested, and radiographs of the cervical spine were produced in anteroposterior, lateral and dynamic views. To evaluate the influence of the variables on the emergence of instabilities, univariate and multivariate logistic regression tests were used (p < 0.05). RESULTS: Among the 35 patients evaluated, 13 (37.1%) presented a stable cervical spine. Out of the 22 patients with instability, six presented more than one type. Atlantoaxial instability was found in 15 patients, with a mean anterior atlantodental distance of 3.40 mm in the neutral lateral radiographic view and 6.54 mm in the lateral view with flexion. Basilar invagination was found in five patients and subaxial subluxation in seven patients. Two thirds of the asymptomatic patients had instabilities. Bicipital hyperreflexia presented statistically significant correlations with atlantoaxial instability (p = 0.024) and subaxial instability (p = 0.01). Age at diagnosis correlated with subaxial instability (p = 0.02). CONCLUSIONS: The prevalence of cervical instability was 62.9 % (22/35). The most frequent instabilities were: atlantoaxial subluxation (42.9 %), subaxial subluxation (20%) and basilar invagination (14.3%). The correlation between instabilities and clinical signs and symptoms was poor. The patients with subaxial subluxation presented disease onset at a younger age. Dynamic radiography was important for diagnosing atlantoaxial subluxation. | |
27843575 | Effectiveness and safety of TNF inhibitors in adults with juvenile idiopathic arthritis. | 2016 | INTRODUCTION: Many children with juvenile idiopathic arthritis (JIA) continue to have active disease into adulthood. Adults with JIA are a heterogeneous group, and the effects of tumour necrosis factor inhibitor (TNFi) therapies are not well described. This analysis aims to describe treatment outcomes among patients with JIA starting TNFi for the first time in adulthood. METHODS: Patients with arthritis onset <16 years starting their first TNFi therapy were identified from the British Society of Rheumatology Biologics Register. Disease activity outcomes (using 28-joint Disease Activity Score (DAS28) and Health Assessment Questionnaire (HAQ)) are presented at 1 year after start of therapy according to disease pattern. Incidence rates (IR) of adverse events per 1000 person-years (pyrs) were calculated. Outcomes in patients with polyarticular JIA were compared with a cohort (weighted for age and gender) of patients with rheumatoid arthritis (RA). RESULTS: In 443 adults with JIA starting a first TNFi, disease activity over 1 year improved across all measures. There were 58 first serious infections (IR 22.3/1000 pyrs); 4 cardiovascular events (IR 1.4/1000 pyrs); 11 uveitis events (IR 4.0/1000 pyrs) and 16 malignancies (IR 3.9/1000 pyrs). Compared with the weighted RA cohort, disease activity improvement was similar; malignancy rates were lower and uveitis rates much higher. While crude IR were similar, JIA patients had a lower risk of serious infection (HR 0.5 (95% CI 0.3 to 0.9)). CONCLUSIONS: This is the largest study to describe disease activity and safety outcomes in adults with JIA receiving TNFi. Disease activity improved after 1 year in all disease patterns, suggesting TNFi is an effective therapy in this population. | |
27075423 | Rumpel-Leede Phenomenon in a Patient with Laboratory Markers Positive for Sjögren Disease | 2016 Jun 1 | Rumpel-Leede phenomenon is a rare clinical sign involving the appearance of purpura after application of a tourniquet or in noninvasive arterial blood pressure monitoring. This sign has been most commonly associated with hypertensive and diabetic microvascular fragility and thrombocytopenia. We describe a case of Rumpel-Leede phenomenon in an otherwise healthy patient with positive laboratory markers for Sjögren disease, a previously undescribed relationship. We aim to inform physicians of this potential complication in patients with Sjögren disease and suggest special consideration be given to patients with autoimmune diseases with secondary vascular or dermal manifestations. | |
26054431 | Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations w | 2015 Aug | Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation. | |
25466610 | APRIL promotes proliferation, secretion and invasion of fibroblast-like synoviocyte from r | 2015 Mar | Fibroblast-like synoviocyte (FLS) is the ultimate effectual cells in the pathogenesis of rheumatoid arthritis (RA). The current study was undertaken to investigate whether a proliferation-inducing ligand (APRIL) mediates the function of FLS in an animal model of RA. Rat adjuvant-induced arthritis (AA) was induced by intradermal injection of 0.1 ml complete Freund's adjuvant. Synovium APRIL expression was detected by immunohistochemical analysis. The level of APRIL and matrix metalloproteinase (MMP)-9 were assayed by enzyme-linked immunosorbent assay. The expression of APRIL and its receptors (TACI, BCMA and BAFF-R) were assessed by immunofluorescence staining, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and real-time RT-PCR. The effects of APRIL on the function of FLS were investigated by MTT, Quantibody Rat Inflammation Array 1 and transwell assays, respectively. A higher concentration of APRIL was detected in AA synovium homogenate compared with normal group. AA FLS expressed APRIL, TACI, BAFF-R and BCMA at the mRNA levels, whereas only APRIL and BCMA were confirmed to be expressed on membrane by flow cytometry. APRIL stimulated AA FLS proliferation, migration and invasion and the secretion of proinflammatory factors. In addition, FLS cocultured with APRIL-treated B cells or T cells had a significantly greater proliferation than FLS cultured alone. Neutralization of APRIL by the TACI-Ig fusion protein attenuated these stimulating effects of APRIL on FLS. Our data indicate that APRIL may act as an important mediator for facilitating the function of FLS. Blockade of APRIL thus may be a valuable adjunct in the treatment of RA. | |
27318181 | IgG4-related sialadenitis and Sjögren's syndrome. | 2017 Mar | IgG4-related disease (IgG4-RD) has emerged as a new entity in the last decade. It comprises numerous conditions previously thought to be unrelated. Macroscopically, these diseases cause diffuse organ swelling and formation of pseudotumorous masses. Histopathologically, they are characterized by a lymphoplasmacytic infiltrate with increased IgG4+ plasma cells and storiform fibrosis. Despite rapid progress within the last years, our knowledge on these conditions is still fragmented. To date, more than forty organs have been reported to be included in IgG4-RD, and salivary gland involvement is amongst the most common organs affected [IgG4-related sialadenitis (IgG4-RS)]. Interestingly, IgG4-RS shares commonalities with Sjögren's syndrome (SS), like glandular enlargement, sicca symptoms, arthralgias, hypergammaglobulinemia, hypocomplementemia, and circulating antinuclear antibodies. Nonetheless, they differ in that the incidence of anti-Ro and anti-La reactivity is not frequently found in patients with IgG4-RS, their salivary glands are infiltrated by a large number of IgG4+ plasma cells and IgG4-RS symptoms respond promptly to steroids. The aim of this review was to describe the clinical, serological, histopathological and pathophysiological aspects of IgG4-RS in the context of IgG4-RD and highlight the differences between IgG4-RS and SS. | |
26362815 | Biomarkers for Primary Sjögren's Syndrome. | 2015 Aug | Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease with exocrine gland dysfunction and multi-organ involvement. Recent progress in understanding the pathogenesis of pSS offers an opportunity to find new biomarkers for the diagnosis and assessment of disease activity. Screening noninvasive biomarkers from the saliva and tears has significant potential. The need for specific and sensitive biomarker candidates in pSS is significant. This review aims to summarize recent advances in the identification of biomarkers of Sjögren syndrome, trying to identify reliable, sensitive, and specific biomarkers that can be used to guide treatment decisions. | |
27050672 | The EULAR Sjögren's Syndrome Patient-Reported Index is an independent determinant of heal | 2016 Jul | OBJECTIVES: This study was undertaken to evaluate the health-related quality of life (HRQoL) in patients with primary Sjögren's syndrome (pSS) and to identify its predictors among various clinical parameters. METHODS: The EuroQoL-5 dimension (EQ-5D) was used to measure the patients' HRQoL. The utility values of 178 patients with pSS enrolled in a prospective pSS cohort in Korea were analysed and compared with the Korean normative data. The associations among the clinical parameters and utility values were evaluated. RESULTS: The mean utility value of the pSS patients was significantly lower than that of the Korean general population (0.773±0.138 vs. 0.944±0.095, p<0.001). The proportion of patients with problems in the 4 dimensions was significantly higher in the pSS patients than in the general population (anxiety/depression 70.2 vs. 24.2%, pain 78.7 vs. 28.8%, usual activities 37.6 vs. 9.8%, and mobility 40.4 vs. 12.5%, p<0.001). Bivariate correlation analyses revealed that the degree of pain, fatigue, and patient global assessment of the disease was positively correlated with the utility value. The xerostomia inventory score, ocular surface disease index, and the EULAR Sjögren's syndrome patient-reported index (ESSPRI) also correlated with the utility value. On multiple regression analysis, only the ESSPRI remained in the model after stepwise selection adjusted for age and sex (coefficient β =-0.053, p<0.001). CONCLUSIONS: The HRQoL of pSS patients is significantly lower than that of the general population, and the ESSPRI is an independent predictor of the HRQoL in pSS patients. | |
25413736 | Severe hyperferritinemia--a clue for severe hepatitis in a patient with adult-onset Still' | 2016 Mar | A 19-year old previously healthy man developed the adult-onset Still's disease (AOSD) with high ferritin levels. Corticosteroids induced clinical remission with resolution of fever, arthritis, and rash. While tapering corticosteroids, the patient developed severe liver enzymes elevation, very high ferritin levels and, subsequently, acute liver failure. After other causes of liver disease (infections, metabolic, autoimmune hepatitis, lymphoma, and hemophagocytosis) were excluded, severe hepatitis was attributed to AOSD itself. Cyclosporine induced rapid normalization of liver enzymes and reduction in ferritin levels. Severe hepatitis and very high ferritin levels could be the only manifestation of disease activity in AOSD; therefore, monitoring of liver enzymes and ferritin levels is recommended even after resolution of the clinical symptoms of AOSD. Prompt initiation of cyclosporine can improve liver function and prevent progression to liver failure. | |
25288784 | Psychological profiles in patients with Sjögren's syndrome related to fatigue: a cluster | 2015 May | OBJECTIVE: Fatigue is a highly prevalent and debilitating symptom in the autoimmune disease SS. Although the disease process plays a role in fatigue, psychological factors may influence fatigue and the ability to deal with its consequences. Profiles of co-occurring psychological factors may suggest potential targets for the treatment of fatigue. The aim of this study was to identify psychological profiles in patients with SS and the accompanying levels of fatigue. METHODS: Three hundred patients with primary SS (mean age 57 years, 93% female) completed questionnaires on fatigue (multidimensional fatigue inventory), physical activity cognitions (TAMPA-SK), illness cognitions, cognitive regulation, emotion processing and regulation [Toronto Alexithymia Scale 20, Emotion Regulation Questionnaire (ERQ), Berkeley Expressivity Questionnaire], coping strategies (Brief COPE) and social support. RESULTS: Principal axis factor analysis (oblimin rotation) yielded six psychological factors: social support, negative thinking, positive thinking, emotional expressivity, avoidance and alexithymia (i.e. the inability to differentiate emotions). Using cluster analyses, these factors were grouped in four psychological profiles: functional (39%), alexithymic (27%), self-reliant (23%) and dysfunctional (11%). Irrespective of the psychological profile, the level of fatigue was substantially higher in patients than in the general population. Patients with a dysfunctional or an alexithymic profile reported more fatigue than those with a self-reliant profile. CONCLUSION: Our study in SS yielded four psychological profiles that were differentially associated with fatigue. These profiles can be used to examine determinants and prognosis of fatigue as well as the possibility of customizing cognitive behavioural interventions for chronic fatigue. | |
25586964 | Anti-inflammatory activity of sappanchalcone isolated from Caesalpinia sappan L. in a coll | 2015 Jun | Sappanchalcone, a bioactive flavonoid isolated from the heartwood of Caesalpinia sappan L. possesses anti-inflammatory effects. We studied the efficacy of sappanchalcone in attenuating collagen-induced arthritis (CIA) in a mouse model of rheumatoid arthritis. Sappanchalcone was purified to homogeneity from the chloroform fraction of the methanolic extract of C. sappan, and identified using mass spectrometry and (1)H-nuclear magnetic resonance spectroscopy. CIA-induced male DBA/1J mice were divided into control, sappanchalcone-treated, and methotrexate-treated groups (n = 10 per group). Paw swelling, arthritis severity, radiographic and histomorphometric changes were assessed to measure the protective role of sappanchalcone against chronic disease progression. Sappanchalcone administration significantly reduced clinical arthritis and inflammatory edema in paws. Bone mineral density and trabecular structure were maintained in CIA mice administered sappanchalcone. The levels of pro-inflammatory cytokines (TNF-α, IL-6, and 1L-1β) were significantly lower in the serum of sappanchalcone-treated mice as compared with the control group. Our results suggest that sappanchalcone could be used as an anti-inflammatory and bone-protective agent during the treatment of rheumatoid arthritis. | |
25593329 | Coagulation takes center stage in inflammation. | 2015 Jan 15 | In this issue of Blood, Raghu et al provide exciting new data implicating transglutaminase factor XIII (fXIII) in rheumatoid arthritis in mice. The study presents compelling evidence demonstrating that fXIII contributes to arthritis pathogenesis through distinct mechanisms linked to inflammation and destructive bone loss. | |
28053390 | Effectiveness of arthroscopic elbow synovectomy in rheumatoid arthritis patients: Long-ter | 2016 Oct | OBJECTIVE: To determine the long-term clinical and functional results of arthroscopic elbow synovectomy in rheumatoid arthritis patients with refractory elbow synovitis in terms of improvement in pain, function, and active range of motion (AROM) or arc of motion. METHOD: Fifteen rheumatoid elbows in 13 patients, not responding to DMARD therapy and with radiological changes not more than Larsen grade 3 were taken, who underwent arthroscopic elbow synovectomy. The main outcome measured in forms of Mayo Elbow Performance Scale (MEPS) score, measurement of pain using a Visual Analogue Scale (VAS), radiological angles of elbow, disease activity score (DAS-28), arc of motions (AOM) and complications, which were assessed at follow-up periods of 6 months, 24 months, and 30 months. Statistical analysis was done both qualitatively and quantitatively. Mann-Whitney U test, chi-square test, and Student t test were used as the statistical test for determining significance. RESULTS: In the study group, the improvement was sustained and significant as compared to baseline (VAS 1.28, MEPS 81.07 and mean flexion range 85°) (p value <0.001). No significant complications were encountered postoperatively after elbow synovectomy. CONCLUSION: The study assesses the long-term results of arthroscopic synovectomy in elbow synovitis secondary to rheumatoid arthritis with significant results favoring arthroscopic synovectomy. | |
25936608 | Recommendations on the use of biosimilars by the Brazilian Society of Rheumatology, Brazil | 2015 Sep | The Brazilian Societies of Rheumatology (SBR) and Dermatology (SBD), the Brazilian Federation of Gastroenterology (FBG) and the Brazilian Study Group on Inflammatory Bowel Disease (GEDIIB) gathered a group of their respective specialists on the topic of interest to discuss the most relevant issues regarding the clinical use of biosimilar medicines in Brazil. The main aim of that meeting was to prepare a document with recommendations to guide medical specialists and to help the national regulatory and policy-making agencies as concerns the authorization for marketing biosimilars used in autoimmune diseases, such as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, Crohn's disease, juvenile idiopathic arthritis and ulcerative colitis. In addition to considerations on the typical differences between innovator medicines and biosimilars, the specialists established a set of seven recommendations on regulatory advances related to clinical studies, indication extrapolation, nomenclature, interchangeability, automatic substitution and pharmacovigilance. | |
26671547 | The role of high-mobility group box protein 1 in collagen antibody-induced arthritis is de | 2016 Apr | High-mobility group box 1 (HMGB1) has been implicated in angiogenesis and rheumatoid arthritis (RA). The aim of this study was to define more clearly the role of HMGB1 in the synovial angiogenesis and pathogenesis of an immune model of arthritis. BALB/c mice were injected with monoclonal anti-collagen antibody cocktail followed by lipopolysaccharide to induce arthritis. HMGB1 and vascular endothelial growth factor (VEGF) were over-expressed in the areas of the synovium where more inflammation and neoangiogenesis were present. The selective blockade of HMGB1 or VEGF resulted alternatively in a lower severity of arthritis evaluated by the arthritis index. Furthermore, exogenous HMGB1 administration caused a worsening of arthritis, associated with VEGF up-regulation and increased synovial angiogenesis. The selective inhibition of VEGF also resulted in no induction of arthritis in mice receiving exogenous HMGB1. Cytokine enzyme-linked immunosorbent assay (ELISA) analyses performed on peripheral blood and synovial fluid demonstrated a significant reduction of interleukin (IL)-1β, IL-6 and tumour necrosis factor (TNF)-α in mice where HMGB1 and VEGF pathways were blocked. Interestingly, the selective blockade of HMGB1 and VEGF resulted in an increase of the peripheral IL-17A concentration. The development of arthritis mediated by HMGB1 and the synovial angiogenesis can be blocked by inhibiting the VEGF activity. The proinflammatory and proangiogenic cytokine IL-17A was increased when HMGB1 is inhibited, but the synovial angiogenesis was nevertheless reduced in this model of arthritis. Taken together, these findings shed new light on the role of this nuclear protein in the pathogenesis of arthritis in an RA-like model. | |
27698704 | Anti-angiogenic effect of total saponins of Rhizoma Dioscorea nipponica on collagen induce | 2016 Oct | Rheumatoid arthritis (RA) is a common chronic autoimmune and incurable disease. The aim of the present study was to investigate the therapeutic effect and mechanism of the total saponins of Rhizoma Dioscorea nipponica (TSRDN) in RA. A collagen induced-arthritis (CIA) rat model was established. CIA rats were randomly divided into three groups and lavaged with an equal volume of solvent (CIA group), TSRDN (25 mg/kg/day, RDN group) and tripterygium (TP; 12 mg/kg/day, TP group) for 21 days, respectively. Normal rats served as a control group. Hematoxylin-eosin (HE) staining was used to observe the histopathological injury of synovial tissues. The level of CD31, which used for marking and counting, micro vessel density (MVD) and the expression levels of vascular endothelial growth factor (VEGF) and signal transducer and activator of transcription 3 (STAT3) were detected by immunohistochemical analysis. Additionally, the DNA-binding activity of nuclear factor-κB (NF-κB) was determined using an ELISA kit. HE staining showed obvious synovial hyperplasia, inflammatory cell infiltration, pannus formation, cartilage and bone erosion in the CIA group rats. In addition, compared with control group, the level of MVD, the expression of VEGF and STAT3, and the DNA-binding activity of NF-κB were all increased in CIA group rat synovial tissue (all P<0.01); however, TSRDN or tripterygium were able to inhibit these changes (all P<0.01). It was speculated that TSRDN may prevent angiogenesis by inhibiting the expression of STAT3 and the DNA-binding activity of NF-κB p65, thereby potentially improving CIA. | |
26352162 | TSP-1 Deficiency Alters Ocular Microbiota: Implications for Sjögren's Syndrome Pathogenes | 2015 Sep | PURPOSE: The potential role of commensals as triggering factors that promote inflammation in dry eye disease has not been explored. The objective of this study was to evaluate whether ocular microbiota changes with the onset of dry eye disease in thrombospondin-1-deficient (TSP-1(-/-)) mice, a strain that develops Sjögren's syndrome-like disease. METHODS: Conjunctival swabs were collected from TSP-1(-/-) and C57BL/6 mice and analyzed for bacterial presence. Opsonophagocytosis of the bacterial conjunctival isolates derived from the aged TSP-1(-/-) mice by neutrophils derived from either TSP-1(-/-) or C57BL/6 bone marrow was evaluated. The bactericidal activities of TSP-1-derived peptide were examined. RESULTS: We found that in TSP-1(-/-) mice, the conjunctival colonization with Staphylococcus aureus and coagulase negative staphylococci sp (CNS) species was significantly increased with aging and preceded that of the wild-type C57BL/6 control mice. This correlated with increased neutrophil infiltration into the conjunctiva of the TSP-1(-/-) mice, suggesting that TSP-1 plays a significant role in regulating immunity to commensals. Accordingly, the TSP-1(-/-) PMNs opsonophagocytozed the ocular commensals less efficiently than the TSP-1-sufficient neutrophils. Furthermore, a TSP-1-derived peptide, 4N1K, exhibited significant antimicrobial activity when compared to a control peptide against commensal sp. CONCLUSION: These studies illustrate that alterations in the commensal frequency occur in the early stages of development of Sjögren's-like pathology and suggest that interventions that limit commensal outgrowth such as the use of TSP-1-derived peptides could be used for treatment during the early stages of the disease to reduce the commensal burden and ensuing inflammation. |