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

ID PMID Title PublicationDate abstract
28399156 Presence of IL-17 in synovial fluid identifies a potential inflammatory osteoarthritic phe 2017 PURPOSE: Osteoarthritis (OA) is a common and heterogeneous arthritic disorder. Patients suffer pain and their joints are characterized by articular cartilage loss and osteophyte formation. Risk factors for OA include age and obesity with inflammation identified as a key mediator of disease pathogenesis. Interleukin-17A (IL-17) is a pro-inflammatory cytokine that has been implicated in inflammatory diseases such as rheumatoid arthritis. IL-17 can upregulate expression of inflammatory cytokines and adipocytokines. The aim of this study was to evaluate IL-17 levels in the synovial fluid of patients with end-stage knee and hip OA in relation to inflammation- and pain-related cytokines and adipocytokines in synovial fluid and serum, and clinical and radiographic disease parameters. METHODS: This is a cross-sectional study of 152 patients undergoing total hip and knee arthroplasty for OA. IL-17, IL-6, leptin, adiponectin, visfatin, resistin, C-C Motif Chemokine Ligand 2 (CCL2), C-C Motif Chemokine Ligand 7 (CCL7) and nerve growth factor (NGF) protein levels were measured in synovial fluid and serum using enzyme-linked immunosorbent assay (ELISA). Baseline characteristics included age, sex, body mass index, co-morbidities, pain and function, and radiographic analyses (OA features, K&L grade, minimal joint space width). RESULTS: 14 patients (9.2%) had detectable IL-17 in synovial fluid. These patients had significantly higher median concentrations of IL-6, leptin, resistin, CCL7 and NGF. Osteophytes, sclerosis and minimum joint space width were significantly reduced in patients with detectable IL-17 in synovial fluid. No differences were found in pain, function and comorbidities. IL-17 concentrations in synovial fluid and serum were moderately correlated (r = 0.482). CONCLUSION: The presence of IL-17 in the synovial fluid therefore identifies a substantial subset of primary end-stage OA patients with distinct biological and clinical features. Stratification of patients on the basis of IL-17 may identify those responsive to therapeutic targeting.
28552625 The current status and unmet needs in the management of psoriatic arthritis: Viewpoint fro 2018 May BACKGROUND/PURPOSE: To analyze the real-world clinical practice for the treatment of psoriatic arthritis (PsA) and to assess physicians' prescription, difficulties in diagnosis, therapeutic strategy, rationales for biologic therapies and unmet needs in Taiwan. METHODS: We conducted a nationwide cross-sectional observational study by face-to-face in depth interviews with 50 rheumatologists and 30 dermatologists who took care of patients with PsA. RESULTS: The major procedures for recognizing PsA included joint, skin and nail examinations, radiographic imaging, and medical history. More dermatologists established the diagnosis when psoriatic patients with arthritis didn't present with rheumatoid factors (p < 0.05). For milder arthritis, physicians tended to prescribe etanercept in combination with conventional disease-modifying antirheumatic drugs (DMARDs). The efficacy, safety, retention rate, and non-parenteral administration are the major concerns of physicians which are also the primary unmet needs in the current management of PsA. CONCLUSION: This survey showed the status quo in Taiwan of the clinical management for PsA including diagnostic difficulties, therapeutic consideration, rationales for biologic DMARDs selection and unmet needs in treatment. It has indicated that interdisciplinary collaboration may further improve the quality for PsA care. These results may help establish new strategy to develop next generation biologics.
28056922 Herbal formula Xian-Fang-Huo-Ming-Yin regulates differentiation of lymphocytes and product 2017 Jan 5 BACKGROUND: Xian-Fang-Huo-Ming-Yin (XFHM), a traditional herbal formula, has been used to treat sores and carbuncles for hundreds of years in Asia. Nowadays, its clinical effects in treatment of rheumatoid arthritis (RA) have been validated. In this study, we want to study its possible molecular mechanisms of regulating the differentiation of lymphocytes and production of pro-inflammatory cytokines in collagen-induced arthritis (CIA) mice for RA treatment. METHODS: A high performance liquid chromatography-electrospray ionization/mass spectrometer (HPLC-ESI/MS(n)) system was used to analyze the constituents of XFHM granules. An arthritics mouse model was induced by collagen and leflunomide (LEF) was used as a positive control medicine. Pathological changes at the metatarsophalangeal joint were studied through Safranin O and immunohistochemical staining. The differentiation of T, B and NK cells was examined by flow cytometry and pro-inflammatory cytokines were assayed using an Inflammation Antibody Array assay. The expression of key molecules of the nuclear factor κB (NF-κB) and Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathways in spleen were studied by western-blot analysis. RESULTS: In our study. 21 different dominant chemical constituents were identified in XFHM. Treatment with XFHM suppressed the pathological changes in arthrosis of CIA. Additionally, XFHM down-regulated the proliferation and differentiation of CD3(+) T cells and CD3(-)CD19(+) B cells significantly. However, XFHM had no significant effect on CD3(-)NK1.1(+) NK cells. Further study showed that the production of pro-inflammatory cytokines had been suppressed by inhibiting the activation of NF-κB and JAK/STAT signaling. CONCLUSIONS: XFHM can regulate and maintain the immunologic balance of lymphocytic immunity and inhibit the production of pro-inflammatory cytokines, thus suppressing the pathological changes of RA. Therefore, XFHM may be used as an application of traditional medicine against RA in modern complementary and alternative therapeutics.
29217121 Diagnostic and treatment effects of sialendoscopy for patients with swelling of the paroti 2018 Aug Between August 2009 and May 2016, 74 patients underwent sialoendoscopic surgery. 32 patients had parotid gland disease and 9 patients had intermittent swelling of the parotid gland and sialoliths were not detected with CT imaging. 4 patients were diagnosed with idiopathic Stensen's duct stenosis. Sialendoscopy directly confirmed Stensen's duct stenosis in 2 patients. However, the sialendoscope was unable to be inserted in the other 2 patients, who had stenosis of the orifice of the Stensen's duct. Balloon expansion of the duct was performed in these 2 patients and a steroid drug was injected into the duct in one patient. Complete remission was archived in one patient treated with sialendoscopy. Three patients had sialolithiasis. Microsialoliths and/or white floating matter was observed and removed using sialendoscopy. All patients experienced complete remission. In cases of Sjögren syndrome and recurrent parotitis, sialendoscopic surgery was performed, but the symptoms showed no improvement. For patients with microsialoliths, sialendoscopy may be most useful for diagnosis and treatment when the sialoliths are not detected with CT imaging. At present, sialendoscopic surgery have limitation in the treatment of Stensen's duct stenosis and may similarly have limitation in the treatment of Sjögren's syndrome and recurrent parotitis.
28390965 Autoantibodies, detection methods and panels for diagnosis of Sjögren's syndrome. 2017 Sep The presence of autoantibodies is one of several hallmarks of Sjögren's Syndrome, the detection of serum autoantibodies has a central role in the diagnosis and classification of Sjögren's syndrome. In this review, we will discuss autoantibodies that are helpful in the diagnosis of Sjögren's syndrome. This includes the traditional autoantibodies for disease classification (ANA, Anti-Ro/SSA, Anti-La/SSB, RF), autoantibodies identified from mouse models (Anti-SP1, Anti- PSP, Anti-CA6, and anti-alpha fodrin) and autoantibodies associated with other autoimmune disease (ACA, AMA, and Anti-CCP). We will also review the methods for the detection of autoantibodies and associated challenges for clinical results reporting. The significance of using an autoantibody panel for the diagnosis of SS will be also be reviewed.
28284305 Autodisplay of the La/SSB protein on LPS-free E. coli for the diagnosis of Sjögren's synd 2017 May The objective of this study was to present an immunoassay for the diagnosis of Sjögren's syndrome based on the autodisplayed La/SSB protein on the outer membrane of intact E. coli (strain UT-5600) and LPS-free E. coli (ClearColi™). As the first step, an autodisplay vector (pCK002) was transfected into intact E. coli and LPS-free E. coli for comparison of efficiency of autdisplay of La/SSB. The maximal level of La/SSB expression was estimated to be similar for LPS-free E. coli and intact E. coli at different optimal induction periods. Intact E. coli was found to grow twofold faster than LPS-free E. coli, and the maximal level of expression for LPS-free E. coli was obtained with a longer induction period. When the zeta potential was measured, both intact E. coli and LPS-free E. coli showed negative values, and the autodisplay of negatively charged La/SSB protein (pI<7) on the outer membrane of intact E. coli and LPS-free E. coli resulted in a slight change in zeta potential values. E. coli with autodisplayed La/SSB protein was used for an immunoassay of anti-La/SSB antibodies for the diagnosis of Sjögren's syndrome. The surface of E. coli with the autodisplayed antigen was modified with rabbit serum and papain to prevent false positive signals because of nonspecific binding of unrelated antibodies from human serum. LPS-free E. coli with autodisplayed La/SSB protein yielded sensitivity and selectivity of 81.6% and 78.6%, respectively. The Bland-Altman test showed that the immunoassays based on LPS-free E. coli and intact E. coli with autodisplayed La/SSB protein were statistically equivalent to a clinical immunoassay for detection of anti-La/SSB antibodies (confidence coefficient 95%).
27538522 Elevated level of circulating CD4(+)Helios(+)FoxP3(+) cells in primary Sjogren's syndrome 2017 Jul OBJECTIVE: This study was designed to investigate the expression of regulatory T cells in primary Sjögren's Syndrome (pSS) and to evaluate the clinical role of CD4 (+) Helios(+) FoxP3(+) cells in pSS patients. METHODS: CD4 (+) FoxP3(+ )T cells in the peripheral blood of 39 pSS patients and 30 healthy controls were measured by flow cytometry and CD25 and Helios expression were also analyzed. The repression ability of CD4 (+) CD25(hi) cells was tested in vitro. Clinical information of pSS patients was retrospectively collected and their correlations with circulating Treg cells were analyzed. Cytokine levels in plasma were measured by ELISA and correlations with Helios(+) FoxP3(+ )cells were also detected. RESULTS: Circulating FoxP3(+ )and Helios(+) FoxP3(+ )cells were elevated in pSS patients compared with controls. The suppression function of CD4 (+) CD25(hi) cells is not different between two groups. There are inverse correlations between Helios(+) FoxP3(+ )percentage and ESR, IgG, IgM and ESSDAI. Anti-SSB(-) patients possess higher level of Helios(+) FoxP3(+ )cells than anti-SSB(+ )patients. IL-6, IFNγ and IFNα levels were increased in pSS plasma and there were positive correlations between the levels of IFNγ/IFNα and percentage of Helios(+) FoxP3(+ )cells. CONCLUSION: Circulating Helios (+) FoxP3(+) cells were elevated in pSS patients and may contribute to suppressing autoimmunity in pSS patients.
28771678 Lymphocytic hidradenitis: A distinctive histopathological finding of annular erythema of S 2018 Aug BACKGROUND/OBJECTIVES: Lymphocytic hidradenitis is a non-specific histopathological feature observed in many dermatoses such as lupus erythematosus, morphea or scleroderma. When it occurs it is usually accompanied by the other distinctive histological features of those conditions. Isolated lymphocytic hidradenitis is uncommon and its clinical features and associated underlying medical conditions are still undetermined. METHODS: We performed a retrospective review of patients who clinically presented with annular erythema between 2000 and 2016. Altogether, 30 patients with a histopathological presentation of isolated lymphocytic hidradenitis were identified. Their following characteristics were recorded: clinical features, number and localisation of lesions, serology and other associated medical conditions. RESULTS: Isolated lymphocytic hidradenitis was found most frequently in middle-aged women. Most patients (n = 28, 93%) presented with many annular erythematous patches and plaques with mild pruritus; 22 (73%) had the SS-A antibody and 17 (57%) met the diagnostic criteria of Sjögren syndrome. Among these patients, 11 had primary and six had secondary Sjögren syndrome associated with systemic lupus erythematosus. Altogether 15 (50%) patients tested positive for a high titre of the antinuclear autoantibody. Other underlying diseases identified during the follow-up period include cryoglobulinaemia, angioimmunoblastic T-cell lymphoma, autoimmune hepatitis, hepatitis C infection and toxic thyroid goitre. CONCLUSIONS: Lymphocytic hidradenitis is a microscopic finding associated with annular erythemas of Sjögren syndrome. Systemic survey for sicca symptoms and work up for autoimmune diseases, including antinuclear antibodies, SS-A, SS-B antibodies, cryoglobulin, lymphoma, viral and autoimmune hepatitis should be performed to facilitate the correct diagnosis.
28564491 Attenuation of Follicular Helper T Cell-Dependent B Cell Hyperactivity by Abatacept Treatm 2017 Sep OBJECTIVE: To assess the effect of abatacept (CTLA-4Ig), which limits T cell activation, on homeostasis of CD4+ T cell subsets and T cell-dependent B cell hyperactivity in patients with primary Sjögren's syndrome (SS). METHODS: Fifteen patients with primary SS treated with abatacept were included. Circulating CD4+ T cell and B cell subsets were analyzed by flow cytometry at baseline, during the treatment course, and after treatment was completed. CD4+ effector T cell subsets and Treg cells were identified based on expression of CD45RA, CXCR3, CCR6, CCR4, CXCR5, programmed death 1, inducible costimulator (ICOS), and FoxP3. Serum levels of anti-SSA/anti-SSB and several T cell-related cytokines were measured. Expression of ICOS and interleukin-21 (IL-21) protein was examined in parotid gland tissue at baseline and after treatment. Changes in laboratory parameters and associations with systemic disease activity (EULAR Sjögren's Syndrome Disease Activity Index [ESSDAI]) over time were analyzed using generalized estimating equations. RESULTS: Abatacept selectively reduced percentages and numbers of circulating follicular helper T (Tfh) cells and Treg cells. Other CD4+ effector T cell subsets were unaffected. Furthermore, expression of the activation marker ICOS by circulating CD4+ T cells and expression of ICOS protein in parotid gland tissue declined. Reduced ICOS expression on circulating Tfh cells correlated significantly with lower ESSDAI scores during treatment. Serum levels of IL-21, CXCL13, anti-SSA, and anti-SSB decreased. Among circulating B cells, plasmablasts were decreased by treatment. After cessation of treatment, all parameters gradually returned to baseline. CONCLUSION: Abatacept treatment in patients with primary SS reduces circulating Tfh cell numbers and expression of the activation marker ICOS on T cells. Lower numbers of activated circulating Tfh cells contribute to attenuated Tfh cell-dependent B cell hyperactivity and may underlie the efficacy of abatacept.
28215033 Anti-mutated citrullinated vimentin antibodies in antiphospholipid syndrome: diagnostic va 2017 Apr Antiphospholipid antibodies (aPLs) are a heterogeneous group of autoantibodies essential for the diagnosis of antiphospholipid syndrome (APS) but do not predict clinical manifestations or disease progression. Hence, the co-presence of other antibodies may prove useful. Autoimmunity directed toward vimentin and other citrullinated peptides was established in rheumatoid arthritis (RA) and in other autoimmune conditions including systemic lupus erythematosus (SLE). We have previously described the presence of autoantibodies directed against vimentin/cardiolipin complex in patients with antiphospholipid syndrome (APS), but there are no data on the role of citrullinated vimentin in APS. Thus, we evaluated the prevalence and clinical significance of anti-MCV in APS patients. The study group consisted of 79 unselected outpatients with APS. Control groups included 25 patients with SLE, 30 patients with RA, and 20 healthy subjects age- and sex-matched. To detect anti-MCV, anti-vimentin, anti-vimentin/cardiolipin, and anti-CCP2 antibodies, commercial or homemade enzyme-linked immunosorbent assays (ELISA) were performed. Anti-MCV antibodies were found in a high percentage of APS patients (26.6%). A significant correlation between anti-MCV and anti-vimentin/cardiolipin serum levels was observed (p = 0.029). Moreover, vimentin reactivity was increased by its citrullination or conjugation with cardiolipin (p = 0.01 and p < 0.001, respectively). Interestingly, anti-MCV was found associated with the presence of arthritis (p = 0.011) and anti-vimentin/cardiolipin was highly specific for the presence of arterial or venous thrombosis in APS (p = 0.003 and p = 0.002, respectively). The detection of additional autoantibodies may contribute to clinical assessment of APS patients. Citrullination may occur in APS and play a role in the pathogenesis of this condition. KEY POINTS: •Anti-MCV antibodies can be found in APS patients and are associated with the presence of arthritis. •Anti-vimentin/cardiolipin is strongly associated with the presence of thrombosis (both arterial and venous). •Citrullination occurs in APS, participate in disease pathogenesis, and influence clinical picture.
29326694 The Fos-Related Antigen 1-JUNB/Activator Protein 1 Transcription Complex, a Downstream Tar 2017 Dysfunction of T helper 17 (Th17) cells leads to chronic inflammatory disorders. Signal transducer and activator of transcription 3 (STAT3) orchestrates the expression of proinflammatory cytokines and pathogenic cell differentiation from interleukin (IL)-17-producing Th17 cells. However, the pathways mediated by STAT3 signaling are not fully understood. Here, we observed that Fos-related antigen 1 (FRA1) and JUNB are directly involved in STAT3 binding to sites in the promoters of Fosl1 and Junb. Promoter binding increased expression of IL-17 and the development of Th17 cells. Overexpression of Fra1 and Junb in mice resulted in susceptibility to collagen-induced arthritis and an increase in Th17 cell numbers and inflammatory cytokine production. In patients with rheumatoid arthritis, FRA1 and JUNB were colocalized with STAT3 in the inflamed synovium. These observations suggest that FRA1 and JUNB are associated closely with STAT3 activation, and that this activation leads to Th17 cell differentiation in autoimmune diseases and inflammation.
28298526 The AP-1 Transcription Factor c-Jun Promotes Arthritis by Regulating Cyclooxygenase-2 and 2017 May 1 Activation of proinflammatory macrophages is associated with the inflammatory state of rheumatoid arthritis. Their polarization and activation are controlled by transcription factors such as NF-κB and the AP-1 transcription factor member c-Fos. Surprisingly, little is known about the role of the AP-1 transcription factor c-Jun in macrophage activation. In this study, we show that mRNA and protein levels of c-Jun are increased in macrophages following pro- or anti-inflammatory stimulations. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment cluster analyses of microarray data using wild-type and c-Jun-deleted macrophages highlight the central function of c-Jun in macrophages, in particular for immune responses, IL production, and hypoxia pathways. Mice deficient for c-Jun in macrophages show an amelioration of inflammation and bone destruction in the serum-induced arthritis model. In vivo and in vitro gene profiling, together with chromatin immunoprecipitation analysis of macrophages, revealed direct activation of the proinflammatory factor cyclooxygenase-2 and indirect inhibition of the anti-inflammatory factor arginase-1 by c-Jun. Thus, c-Jun regulates the activation state of macrophages and promotes arthritis via differentially regulating cyclooxygenase-2 and arginase-1 levels.
28293448 Serum calreticulin as a novel biomarker of juvenile idiopathic arthritis disease activity. 2017 Mar OBJECTIVE: This study aimed to investigate the relations between calreticulin (CRT) serum level and both disease activity and severity parameters in juvenile idiopathic arthritis (JIA). MATERIAL AND METHODS: In this study, 60 children with JIA and 50 age-and-sex-matched healthy subjects were enrolled. The assessment of the disease activity was done using juvenile arthritis disease activity score 27 (JADAS-27). The assessment of disease severity was done via gray-scale ultrasonography (US) and power Doppler US (PDUS). Enzyme-linked immunosorbent assay (ELISA) was used to assay the serum level of human CRT. RESULTS: The mean serum CRT levels in JIA patients was 8.6±1.2 ng/mL and showed a highly significant increase (p=0.001) as compared to the mean serum levels in the controls (5.02±0.77 ng/mL). There were statistically significant positive correlations between the serum CRT levels and disease duration, tender joint count, swollen joint count, visual analog scale, erythrocyte sedimentation rate, JADAS-27, C-reactive protein, rheumatoid factor titer, and ultrasonographic grading for synovitis and neovascularization. CONCLUSION: Elevated serum CRT levels in JIA patients and its correlations with JIA disease activity and severity parameters signified that CRT might be used as a novel biomarker for disease activity and severity in JIA.
29019640 Spine Conditions: Mechanical and Inflammatory Low Back Pain. 2017 Oct Mechanical low back pain (LBP) is an injury or derangement of an anatomic structure in the low back. When evaluating patients with LBP, clinicians should maintain clinical suspicion for vertebral fracture, cancer, and cauda equina syndrome. Management includes patient education focused on exercise, massage, and behavioral approaches such as cognitive behavioral therapy. Acupuncture can be an effective alternative and specific herbal supplements may provide short-term pain relief. The prognosis for patients with mechanical LBP is good. Inflammatory LBP is pain resulting from a systemic inflammatory condition, often referred to as axial spondyloarthritis. Ankylosing spondylitis is chronic inflammatory LBP characterized by early onset (mean age 24 years), with a higher prevalence in men. Five clinical parameters can help identify inflammatory LBP: improvement with exercise, pain at night, insidious onset, onset at younger than 40 years, and no improvement with rest. Management of inflammatory LBP typically includes nonsteroidal anti-inflammatory drugs and structured exercise programs, with emphasis on the involvement of a rheumatology subspecialist. Spondyloarthritis is associated with other rheumatic or autoimmune conditions, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. These should be considered when evaluating patients with inflammatory LBP.
28925103 Autoimmune diseases involving skin and intestinal mucosa are more frequent in adolescents 2017 Dec Evidence has emerged about the relationship between atopic dermatitis (AD) and autoimmune diseases, but the underlying mechanism of this association is complex and still unclear. Recent epidemiological data from the published work suggest a positive correlation. The aim of this review is to analyze the frequency of co-occurrence of AD and autoimmune diseases. Our systematic review included 22 articles from PubMed describing the reciprocal association between AD and autoimmune diseases. Although not all the studies achieved statistically significant results, patients suffering from autoimmune diseases involving skin and intestinal mucosa, such as vitiligo, alopecia areata, celiac disease and inflammatory bowel diseases, showed a higher risk to have AD as comorbidity. In contrast, patients with rheumatological autoimmune disorders did not show a significant correlation with AD. By analyzing the occurrence of autoimmune disorders in patients with AD, we confirmed a positive correlation between AD and autoimmune diseases involving skin and intestinal mucosa, but also with systemic lupus erythematosus, while the association between AD and type 1 diabetes, autoimmune thyroiditis and rheumatoid arthritis showed conflicting results. Further investigations are need to explain the mechanism underlying the observed comorbidity between AD and autoimmune diseases and to develop targeted prevention strategies and treatment.
28697227 Postoperative Pyoderma Gangrenosum Following Video-Assisted Thoracic Surgery. 2017 Jul 1

Pyoderma gangrenosum (PG) is a neutrophilic, ulcerative dermatosis that can develop at sites of cutaneous trauma, including surgical incisions, a phenomenon known as pathergy. The characteristic lesion is a painful, rapidly expanding ulceration with a violaceous undermined border.1 A biopsy taken from the expanding violaceous border shows predominantly neutrophilic dermal inflammation with neutrophilic abscess formation.

The etiology of PG appears to be variable among patients, as about a half of the reported cases are associated with systemic disease such as inflammatory bowel disease, rheumatoid arthritis, or myeloproliferative disorders, while the other half seem to be idiopathic.2 PG is difficult to diagnose as other etiologies, including infectious, vasculitic, and other inflammatory dermatoses, must be excluded.1 Histopathologic and biochemical markers of PG, such as dermal neutrophilic infiltrate or overexpression of interleukin-8,3 respectively, are not pathognomonic. Given that several drugs, such as hydralazine, mesalamine, and sunitinib, are reportedly associated with PG, failure to recognize this association and stop these medications may delay diagnosis and therapy. We report a case of idiopathic postoperative PG following video-assisted thoracic surgery (VATS).

J Drugs Dermatol. 2017;16(7):711-713.

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28664144 Acute toxicity and genotoxicity of fermented traditional medicine oyaksungi-san. 2017 Jun BACKGROUND: The traditional medicine oyaksungi-san (OY) has been prescribed in East Asia for hundreds of years for the treatment of stroke, paralysis, and ataxia. OY also has therapeutic effects on arthralgia, myalgia, and rheumatoid arthritis, and recent studies have shown its protective effects against apoptosis of hippocampal cells and its anti-inflammatory effects on the peripheral blood cells of patient with cerebral infarction. Many studies have explored the use of traditional medicine and herb materials in the development of safe, novel, and effective pharmaceuticals with fewer side effects. These efforts commonly adopt a bioconversion tool for fermentation with beneficial microbes. However, only pharmaceuticals with high levels of safety and low levels of toxicity can be used in healthcare system. METHODS: OY water extract was fermented with Lactobacillus and assayed for acute toxicity and genotoxicity. Single dose acute toxicity, bacterial reverse mutation, chromosome aberrations, and micronucleus were observed and assayed in rats, histidine/tryptophan auxotrophic bacteria, Chinese hamster ovary fibroblast cells, and mice bone marrow cells, respectively. RESULTS: All the experimental animals showed no abnormal behavior, clinical signs, body weight increases, or mortality. In the bacterial cultures, no revertant colonies were observed. Morphological and numerical chromosomal aberrations were not found in all metaphases examined. Frequency of induced micronuclei was not significantly increased in all doses applied. CONCLUSION: As a whole, no acute toxicity or genotoxicity were observed in all the assays examined. Therefore, fermented OY is considered to be a safe material that can be used for development of complementary and alternative medicine using bioconversion.
27454420 A quantitative enzyme-linked immunosorbent assay for quantification of secretory immunoglo 2017 Secretory immunoglobulin A (SIgA) in serum is possibly the best index of SIgA presence in mucosal secretions in digestive tract and the mirror of its immunologic barrier against many pathogenic aggressions. The measurement of salivary SigA alone may be affected by total salivary secretion and its final concentration in the gland lumen is probably not useful as an appropriate index of mucosal secretions in the digestive tract. The usefulness of the determination of SigA against various epitopes in serum from patients with various autoimmune disease has been demonstrated. The aetiology of many digestive related disorders could be triggered by an alteration of mucose SIgA barrier. The determination of Igs is important for different liver diseases and specifically the SIgA in autoimmune diseases such as rheumatoid arthritis. We developed an easy and efficient immunologic assay to quantify SIgA in serum samples.
28701761 Antigen-specific immunotherapies in rheumatic diseases. 2017 Sep The main goal of antigen-specific immunotherapy (ASI) in autoimmune and rheumatic diseases is to reprogramme or remove autoreactive cells and/or induce immune tolerance to self-antigens. Current therapies in these diseases either treat symptoms or slow down disease progression but are not yet curative or preventative - disease-specific treatments are urgently needed. In contrast to the nonspecific treatments in current use that induce generalized immune suppression, which is associated with several adverse effects including increased risk of infections, ASIs target a restricted subset of B cells or T cells, and thus do not compromise systemic immunity and host defence. This Review provides a summary of novel approaches for identifying autoepitopes and detecting and targeting autoreactive cells that might help in the development of ASIs. Promising approaches include the use of tolerizing peptides coupled to MHC constructs and/or nanocompounds, tolerizing dendritic cells and antigen-specific vaccines. Following studies in animal models of rheumatoid arthritis and systemic lupus erythematosus, several of these strategies have now entered clinical trials. However, to use these approaches in humans, several important limitations must first be addressed, such as; selecting the proper immunodominant autoantigen; identifying the optimal timing, dosing and route of administration; finding biomarkers for monitoring the therapy; and optimizing methodology.
28532196 Fetal and neonatal involvement in maternal rheumatologic disease. 2018 Aug A pregnancy complicated with rheumatologic diseases can have various influences on the fetus and/or neonate. Maternal systemic lupus erythematosus (SLE) may cause preterm and/or small for gestational age (SGA) delivery and neonatal lupus (NL). Some neonates with NL have congenital heart block (CHB) with increased morbidity and mortality, even requiring pacemakers. Antiphospholipid syndrome may occur with SLE and affect fetal and/or neonatal outcomes. Pregnancy involving primary Sjögren's syndrome (pSS) tends to result in preterm delivery and low birthweight infants. Moreover, CHB is the most challenging complication for neonates delivered by women with pSS. Pregnant women with rheumatoid arthritis (RA) are at an increased risk for delivering a preterm or SGA neonate. In addition, RA drugs may have adverse effects on the fetus and breast-fed neonate. With dermatomyositis/polymyositis, pregnancies are at increased risk for spontaneous abortion, perinatal death, and preterm delivery. At present, overall neonatal survival rates are good for pregnancies involving systemic sclerosis, despite an increased frequency of premature and SGA neonates. In conclusion, maternal rheumatological diseases require careful monitoring to ensure the best possible management for fetal and neonatal outcomes.