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ID PMID Title PublicationDate abstract
26613766 Autoantibodies to citrullinated proteins induce joint pain independent of inflammation via 2016 Apr OBJECTIVE: An interesting and so far unexplained feature of chronic pain in autoimmune disease is the frequent disconnect between pain and inflammation. This is illustrated well in rheumatoid arthritis (RA) where pain in joints (arthralgia) may precede joint inflammation and persist even after successful anti-inflammatory treatment. In the present study, we have addressed the possibility that autoantibodies against citrullinated proteins (ACPA), present in RA, may be directly responsible for the induction of pain, independent of inflammation. METHODS: Antibodies purified from human patients with RA, healthy donors and murinised monoclonal ACPA were injected into mice. Pain-like behaviour was monitored for up to 28 days, and tissues were analysed for signs of pathology. Mouse osteoclasts were cultured and stimulated with antibodies, and supernatants analysed for release of factors. Mice were treated with CXCR1/2 (interleukin (IL) 8 receptor) antagonist reparixin. RESULTS: Mice injected with either human or murinised ACPA developed long-lasting pronounced pain-like behaviour in the absence of inflammation, while non-ACPA IgG from patients with RA or control monoclonal IgG were without pronociceptive effect. This effect was coupled to ACPA-mediated activation of osteoclasts and release of the nociceptive chemokine CXCL1 (analogue to human IL-8). ACPA-induced pain-like behaviour was reversed with reparixin. CONCLUSIONS: The data suggest that CXCL1/IL-8, released from osteoclasts in an autoantibody-dependent manner, produces pain by activating sensory neurons. The identification of this new pain pathway may open new avenues for pain treatment in RA and also in other painful diseases associated with autoantibody production and/or osteoclast activation.
27747567 Analysis and Breakdown of Overall 1-Year Costs Relative to Inpatient and Outpatient Care A 2015 Sep BACKGROUND: The economic burden linked to rheumatoid arthritis (RA) has greatly increased since the inclusion of biotherapies in the therapeutic arsenal. OBJECTIVES: This study aimed first to look at the breakdown of the rheumatoid arthritis patients on biotherapy in Alsace, France, in 2012, then to evaluate the annual cost per treated patient for each management pathway: inpatient care with intravenous biotherapies and/or outpatient care through the use of subcutaneous drugs, and finally to conduct a cost comparison with a focus on infliximab, adalimumab and etanercept. METHODS: This observational study was conducted in Alsace using 2012 health claims data from the DCIR (Données de Consommation Inter Régime) and PMSI (Programme de Médicalisation des Systèmes d'Information) databases, taking into account direct medical and non-medical costs in a real-life setting and from a National Health Insurance perspective. RESULTS: There were 5702 RA patients, i.e. 0.31 % of the Alsace population in 2012, including 1075 subjects (18.85 %) receiving biotherapy treatment. The most frequently prescribed biotherapies were etanercept and adalimumab. The estimated overall cost of care of these 5702 patients was €30.3 million, with about 50 % for the care of the 18.85 % patients on biotherapy. Average costs for inpatient, outpatient and mixed care ranged from €14,197 to €16,873 per patient per year. Annual average cost for management of a single RA patient with infliximab was significantly higher than with adalimumab and etanercept: €16,480 versus €14,116 and €14,338, respectively. CONCLUSION: These findings confirm the trends of initial modelling approaches and quantify the cost difference between various biotherapy management pathways.
25575936 Emerging drugs for the treatment of axial and peripheral spondyloarthritis. 2015 Mar INTRODUCTION: The topic under discussion is of strong relevance to the field of spondyloarthritis (SpA) because, in addition to established biological, there are new promising compounds. The reason for the review is to put all available data together to allow for an overview on recent developments and to especially inform readers about emerging drugs, biologics and small molecules in the field of SpA. AREAS COVERED: This review on new therapies in axial and peripheral SpA comprising psoriatic arthritis (PsA) shows, that, in addition to the established anti-TNF agents infliximab, etanercept, adalimumab, golimumab, certolizumab and the first biosimilar approved in the EU, there are at least two emerging biologics in the field of SpA: ustekinumab, a compound targeting IL12/IL-23 via the p40 subunit of both cytokines works for psoriasis and PsA and probably also for Crohn's disease, and the anti-IL-17 antibody secukinumab which has also been shown to work in psoriasis, both compounds seem to also work in ankylosing spondylitis. In addition, the potential of two small molecules, apremilast a phoshodiesterase4 inhibitor and tofacitinib, a januskinase inhibitor is discussed. EXPERT OPINION: Since, in contrast to rheumatoid arthritis, the therapeutic array in SpA is currently limited to TNF-blockers, and since there is still an unmet need because some patients do not respond to anti-TNF therapy at all or they loose response, new agents with a different mechanism of action are eagerly awaited.
25427620 Metabolic syndrome and chronic arthritis: effects of anti-TNF-α therapy. 2015 Nov TNF-α plays a key role in the inflammatory cytokine cascade involved in the pathogenesis of chronic arthritis, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Systemic inflammation and the increased production of pro-inflammatory cytokines in these patients may favor the onset of metabolic syndrome. In patients affected by chronic arthritis, TNF-α is considered as one of the factors responsible for favouring insulin resistance and dyslipidemia, which are important features of the metabolic syndrome. Even if TNF-α is a single player in the great molecular cauldron of inflammation, the use of TNF-α inhibitors may be an important approach for not only treating articular and cutaneous symptoms but also for ameliorating glucose and lipid metabolism. Nevertheless, further research and clinical trials are needed to better determine the effects of biologic therapies on metabolic components in chronic arthritis patients and to identify the most appropriate strategies on the basis of the comorbidities in these patients.
27035125 Extracts of Bauhinia championii (Benth.) Benth. attenuate the inflammatory response in a 2016 May Rheumatoid arthritis is considered a serious public health problem, which is commonly treated with traditional Chinese or herbal medicine. The present study evaluated the effects of Bauhinia championii (Benth.) Benth. extraction (BCBE) on a type II collagen-induced arthritis (CIA) rat model. Wistar rats with CIA received either 125 or 500 mg/kg BCBE, after which, paw swelling was markedly suppressed compared with in the model group. In addition, BCBE significantly ameliorated pathological joint alterations, including synovial hyperplasia, and cartilage and bone destruction. The protein and mRNA expression levels of interleukin (IL)‑6, IL‑8, tumor necrosis factor‑α and nuclear factor‑κB in synovial tissue were determined by immunohistochemical staining, western blot analysis and reverse transcription‑polymerase chain reaction. The results demonstrated that the expression levels of these factors were significantly downregulated in the BCBE‑treated group compared with in the model group. These results indicated that BCBE may exert an inhibitory effect on the CIA rat model, and its therapeutic potential is associated with its anti-inflammatory action.
25839035 Assessment of the body composition and parameters of the cardiovascular risk in juvenile i 2015 The study was aimed to evaluate cardiovascular risk parameters, body mass index (BMI) centiles for sex and age, and body fat percentage using the electric bioimpedance method in children with juvenile idiopathic arthritis (JIA). 30 children with JIA participated in the study. A control group included 20 children. Patients were well matched for the age and sex. The body mass and body fat percentage were determined using the segmental body composition analyser; the BMI centiles were determined. All patients had the following parameters determined: lipid profile, hsCRP, homocysteine, and IL-6. The intima media thickness (IMT) was measured. Patients with JIA had significantly lower body weight, BMI, and the BMI centile compared to the control group. The IL-6 levels were significantly higher in patients with JIA compared to the control group. There were no differences between two groups with regard to the lipid profile, % content of the fat tissue, homocysteine levels, hsCRP, and IMT. Further studies are necessary to search for reasons for lower BMI and BMI centile in children with JIA and to attempt to answer the question of whether lower BMI increases the cardiovascular risk in these patients, similarly as in patients with rheumatoid arthritis (RA).
27343199 MZ B cells migrate in a T-bet dependent manner and might contribute to the remission of co 2016 Sep In mice, marginal zone (MZ) B cells are found principally in the MZ of the spleen and characterized as CD23-negative cells, primarily express polyreactive BCRs, high levels of complement receptor-2 and TLRs. Collagen-induced arthritis (CIA) is a commonly used animal model of human rheumatoid arthritis, considered as a Th1-mediated disease. Although the importance of MZ B cells in the initiation of CIA is well established, their role in remission is unexplored. Besides, playing a central role in Th1 cell development, T-box transcription factor (T-bet) has important functions in B cells. T-bet is regulated by IFN-γ and through the BCR and TLR9, the signals that have an impact on regulatory IL-10 production. In this work, we aimed to analyze the contribution of T-bet to the function of IL-10-positive MZ B cells. We demonstrate that during the remission phase of CIA, MZ B cells express an elevated level of T-bet and confirm the existence of IL-10/T-bet coexpressing cells. Moreover, we show that T-bet-expressing MZ B cells migrate toward CXCR3 ligand and secrete IL-10 by inflammatory stimuli. Our data suggest that T-bet might contribute to the remission of CIA by facilitating the regulatory potential of IL-10-positive MZ B cells.
25178696 Anti-inflammatory effects of recombinant human PDCD5 (rhPDCD5) in a rat collagen-induced m 2015 Feb Programmed cell death 5 (PDCD5) was first identified as a gene upregulated in cells undergoing apoptosis. We recently demonstrated the inhibitory effect of PDCD5 on experimentally induced autoimmune encephalomyelitis. In this study, we investigated the anti-inflammatory effects of recombinant human PDCD5 (rhPDCD5) in a rat collagen-induced arthritis (CIA) model. We find that vaccination of collagen II (CII) induced CIA rats with rhPDCD5 significantly delayed the occurrence and reduced the severity of CIA rats. rhPDCD5 also restored the loss of Foxp3(+) regulatory T (Treg) cells and decreased the population of Th1 and Th17 in CIA rats. Simultaneously, rhPDCD5 treatment suppressed the production of pro-inflammatory cytokines (interleukin (IL)-6, IL-17A, tumor necrosis factor-α (TNF-α), and interferon gamma (IFN-γ)) and increased the secretion of anti-inflammatory cytokines (transforming growth factor beta 1 (TGF-β1) and IL-10) in CIA rats. In addition, rhPDCD5 inhibited the ability of CII to induce proliferation of splenocytes and lymph node cells (LNCs) and promoted the CII-activated CD4(+) cell apoptosis. These results of rhPDCD5-treated CIA rats were similar with those of recombinant human TNF-α receptor IgG Fc (rhTNFR:Fc). Thus, to our knowledge, we provide the first evidence that rhPDCD5 may be an efficient approach to diminishing exacerbated immune responses in CIA, indicating its therapeutic potential in the treatment of rheumatoid arthritis and other autoimmune diseases.
26748661 Tetrandrine suppresses articular inflammatory response by inhibiting pro-inflammatory fact 2016 Sep Targeting activated macrophages using anti-inflammatory phytopharmaceuticals has been proposed as general therapeutic approaches for rheumatic diseases. Besides macrophages, chondrocytes are another promising target of anti-inflammatory agents. Tetrandrine is a major bisbenzylisoquinoline alkaloid isolated from Stephania tetrandrae S. Moore which has been used for 2,000 years as an antirheumatic herbal drug in China. Although, the anti-inflammatory effect of tetrandrine has been demonstrated, the mechanism has not been clearly clarified. In this study, we designed a comprehensive anti-inflammatory evaluation system for tetrandrine, including complete Freund's adjuvant (CFA)-induced arthritis rat, LPS-induced macrophage RAW 264.7 cells, and chondrogenic ATDC5 cells. The results showed that tetrandrine alleviated CFA-induced foot swelling, synovial inflammation, and pro-inflammatory cytokines secretion. Tetrandrine could inhibit IL-6, IL-1β, and TNF-α expression via blocking the nuclear translocation of nuclear factor (NF)-κB p65 in LPS-induced RAW 264.7 cells. Moreover, ATDC5 cells well responded to LPS induced pro-inflammatory mediators secretion and tissue degradation, and tetrandrine could also inhibit the production of nitric oxide and prostaglandin E2 , as well as the expression of matrix metalloproteinase (MMP)-3 and tissue inhibitor of metalloproteinase (TIMP)-1 via inhibiting IκBα phosphorylation and degradation. In conclusion, the results showed that one of the anti-inflammatory mechanisms of tetrandrine was inhibiting IκBα and NF-κB p65 phosphorylation in LPS-induced macrophage RAW 264.7 cells and chondrogenic ATDC5 cells. Moreover, we introduce a vigorous in vitro cell screening system, LPS-induced murine macrophage RAW 264.7 cells coupling chondrogenic ADTC5 cells, for screening anti-rheumatic drugs. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1557-1568, 2016.
25854487 Cogan's syndrome and other ocular vasculitides. 2015 Apr The clinical presentation of Cogan's syndrome has been classified as typical and atypical. Like other forms of ocular vasculitis, Cogan's syndrome has been found to have autoimmune origins with antibodies against the cornea, inner ear, and endothelial antigens. Antineutrophil cytoplasmic antibody (ANCA) and rheumatoid factor (RF) have been associated with Cogan's syndrome as well as ocular-involving vasculitides not as strongly associated with the audiovestibular manifestations such as granulomatosis with polyangiitis and rheumatoid arthritis. The mainstay of therapy has been corticosteroids although other methods have been described in recalcitrant disease and to prevent development of systemic sequelae.
26411139 DOES VITAMIN D DEFICIENCY CONTRIBUTE TO THE SEVERITY OF ASTHMA IN CHILDREN AND ADULTS? 2015 Apr Role of vitamin D in the health of bones has been well established for over decades; It was known that its deficiency caused rickets in children and osteomalacia in adults. Later it was discovered that these can be corrected by giving vitamin D. Researchers discovered that vitamin D can be synthesized by exposure to sun. Hence it was also named "the sunshine vitamin". As time passed it was observed that low levels of vitamin D were associated with multiple diseases. This sparked the interest of the scientific community to further the research on vitamin D which led to the studies that started associating vitamin D with various diseases like cancers (prostate, colon and breast), autoimmune diseases (rheumatoid arthritis), infectious diseases (tuberculosis, hepatitis B, hepatitis C, HIV), cardiovascular diseases, mental illnesses (schizophrenia), diabetes mellitus (type 1, type 2 and gestational) and allergic conditions like asthma. With time, more studies were carried out relating levels of vitamin D to development of asthma, asthma exacerbations and risk factors leading to development of asthma like respiratory tract infections with positive associations. A number of studies were carried out which tried to explain the possible molecular mechanisms relating deficiency of vitamin D in pathogenesis of asthma. This review summarizes the role of vitamin D in development of asthma and probable mechanisms relating vitamin D to the pathogenesis of asthma.
26762707 Clinical practice guidelines for oral management of Sjögren disease: Dental caries preven 2016 Apr BACKGROUND: Salivary dysfunction in Sjögren disease can lead to serious and costly oral health complications. Clinical practice guidelines for caries prevention in Sjögren disease were developed to improve quality and consistency of care. METHODS: A national panel of experts devised clinical questions in a Population, Intervention, Comparison, Outcomes format and included use of fluoride, salivary stimulants, antimicrobial agents, and nonfluoride remineralizing agents. The panel conducted a systematic search of the literature according to pre-established parameters. At least 2 members extracted the data, and the panel rated the strength of the recommendations by using a variation of grading of recommendations, assessment, development, and evaluation. After a Delphi consensus panel was conducted, the experts finalized the recommendations, with a minimum of 75% agreement required. RESULTS: Final recommendations for patients with Sjögren disease with dry mouth were as follows: topical fluoride should be used in all patients (strong); although no study results link improved salivary flow to caries prevention, the oral health community generally accepts that increasing saliva may contribute to decreased caries incidence, so increasing saliva through gustatory, masticatory, or pharmaceutical stimulation may be considered (weak); chlorhexidine administered as varnish, gel, or rinse may be considered (weak); and nonfluoride remineralizing agents may be considered as an adjunct therapy (moderate). CONCLUSIONS AND PRACTICAL IMPLICATIONS: The incidence of caries in patients with Sjögren disease can be reduced with the use of topical fluoride and other preventive strategies.
27852384 [Clinical analysis of fourteen cases with neuromyelitis optica spectrum disorders]. 2016 Nov 8 Objective: To analysis the clinical manifestation, radiological data, laboratory findings of neuromyelitis optica spectrum disorders (NMOSD) to help physicians have a deeper understanding of the disease. Methods: The clinical manifestations, radiological data, laboratory findings of NMOSD patients from People's Hospital of Zhengzhou University between June 2015 and June 2016 were retrospectively analyzed. Results: Fourteen patients with NMOSD were enrolled, consisting of 3 males and 11 females. The onset age ranged from 15 to 62 years, in average 39.64. Among them, there was 1 case with history of hyperthyroidism, 3 cases with Sjögren syndrome (SS). Major clinical manifestations were vision loss in 4 cases, nausea and vomiting in 4 cases, limbs numbness and weakness in 6 cases. All the 14 patients were received the cerebrospinal fluidcell surface antigen antibody detection, and the results were strong positive 6 cases (6/14), positive 7 cases (7/14), weak positive 1 case (1/14). Abnormal signals in the thirdventricle, midbrain aqueduct, oblongata, pons and cervical, thoracic spinal cord were found by Magnetic Resonance Imaging (MRI). Fourteen patients were treated with glucocorticoid, among them 8 received immunosuppressive therapy. All the 14 patients were followed up, and 9 patients had different degrees of sequelae, including vision decline in 4 cases, numbness and weakness in 5 cases. Conclusions: Neuromyelitis optica spectrum disorders frequently occur in young female. Clinicians need to consider the possibility of NMOSD for acute or subacute blurred vision, nausea, vomiting, numbness and weakness of limbs or trunk and psychiatric symptoms. NMOSD can not be easily excluded for those special patients with atypical clinical manifestations, and relevant inspections should be performed as far as possible in order to make the correct diagnosis.
26812559 Features of childhood Sjögren's syndrome in comparison to adult Sjögren's syndrome: cons 2016 Mar OBJECTIVES: To describe the clinical features of childhood Sjögren's syndrome (SS) in comparison to adult SS and to evaluate possible child-specific modifications to existing adult criteria for use in diagnosing childhood SS. METHODS: We retrospectively identified children (age <18 years) with SS and compared the clinical, laboratory, and histopathological features of these children based on presence or absence of parotitis. We compared these features to adults with SS and evaluated the applicability of existing classification criteria in diagnosing childhood SS. Child-specific modifications to existing criteria were evaluated. RESULTS: Twenty-six children were included in our childhood SS group. Sixteen children had parotitis at or before presentation. Absence of parotitis was associated with greater degree of organ damage based on SS disease damage index. Compared to 413 adult SS patients, childhood SS was more commonly associated with parotitis, positive serologies, neurologic and nephrologic manifestations, and non-specific features (fever, lymphadenopathy) but less commonly associated with dry mouth and dry eyes. Only a minority of these children met previously established criteria for adult SS. Inclusion of child-specific features such as parotitis and the presence of any focal lymphocytic sialadenitis on minor salivary gland biopsy increased the proportion of children meeting these criteria. CONCLUSIONS: Childhood SS features may be different than adult SS features necessitating child-specific criteria for better diagnosis of childhood SS, a key step towards better understanding the features, prognosis, and outcomes in this disease.
24697199 Successful tocilizumab therapy in seven patients with refractory adult-onset Still's disea 2016 To evaluate the effects of tocilizumab (TCZ) on adult-onset Still's disease (AOSD), we reviewed medical records of seven patients with refractory AOSD treated with TCZ at our institution. TCZ therapy might allow rapid corticosteroid tapering and help maintain remission status, that is, resolution of clinical symptoms and normalization of biomarkers such as CRP and ferritin. Patients, however, should be monitored for the development of macrophage activation syndrome when TCZ is administered for active AOSD.
27872417 Virtual Touch Quantification of the Salivary Glands for Diagnosis of Primary Sjögren Synd 2016 Dec OBJECTIVES: To investigate the value of salivary gland stiffness measured by Virtual Touch quantification (VTQ; Siemens Medical Solutions, Erlangen, Germany) for assessment of primary Sjögren syndrome. METHODS: Fifty-four patients with primary Sjögren syndrome, 35 patients without primary Sjögren syndrome (patients with dry mouth and dry eye symptoms), and 52 healthy control volunteers were included in this study. Patients with primary Sjögren syndrome were classified as early or advanced stage by labial gland biopsies. All participants underwent B-mode sonography, on which the salivary glands (parotid and submandibular) were identified and VTQ measurements of shear wave velocity (SWV) were obtained. The diagnostic performance of SWV was evaluated by sensitivity and specificity at the optimum cutoff point and the area under the receiver operating characteristic curve. RESULTS: For submandibular glands, the mean SWV ± SD values were 2.25 ± 0.34 m/s in patients with early-stage primary Sjögren, 1.84 ± 0.20 m/s in patients without primary Sjögren syndrome, and 1.82 ± 0.27 m/s in healthy controls (P< .001). With cutoff values of 2.15 and 2.10 m/s to separate patients with early-stage primary Sjögren syndrome from those without Sjögren syndrome and healthy controls, the sensitivity and specificity were 77.1% and 85.4% and 79.2% and 83.9%, respectively. For parotid glands, the SWV values were 2.78 ± 0.82 m/s in patients with early-stage primary Sjögren syndrome, 1.93 ± 0.33 m/s, in patients without primary Sjögren syndrome, and 1.85 ± 0.31 m/s in healthy controls (P < .001). With cutoff values of 2.18 and 2.10 m/s to separate patients with early-stage primary Sjögren syndrome from those without Sjögren syndrome and healthy controls, the sensitivity and specificity were 89.3 % and 75.3% and 91.4% and 80.0%. CONCLUSIONS: The VTQ technique might be a useful noninvasive strategy for assessment of salivary glands in the early stage of primary Sjögren syndrome.
27622909 Aquaporin modulators: a patent review (2010-2015). 2017 Jan Since the discovery of aquaporin-1 (AQP1) as a water channel, more than 2,000 articles, reviews and chapters have been published. The wide tissue expression, functional and biological roles have documented the major and essential physiological importance of these channels both in health and disease. Thus, over the years, studies have revealed essential importance of aquaporins in mammalian pathophysiology revealing aquaporins as potential drug targets. Areas covered: Starting from a brief description of the main structural and functional features of aquaporins, their roles in physiology and pathophysiology of different human diseases, this review describes the main classes of small molecules and biologicals patented, published from 2010 to 2015, able to regulate AQPs for diagnostic and therapeutic applications. Expert opinion: Several patents report on AQP modulators, mostly inhibitors, and related pharmaceutical formulations, to be used for treatments of water imbalance disorders, such as edema. Noteworthy, a unique class of gold-based compounds as selective inhibitors of aquaglyceroporin isoforms may provide new chemical tools for therapeutic applications, especially in cancer. AQP4-targeted therapies for neuromyelitis optica, enhancement of AQP2 function for nephrogenic diabetes insipidus and AQP1-5 gene transfer for the Sjogren's syndrome represent promising therapies that deserve further investigation by clinical trials.
27225247 Elevated high-mobility group B1 levels in active adult-onset Still's disease associated wi 2016 Aug High-mobility group box-1 (HMGB1) is a nuclear protein, and such prototypical damage-associated molecular patterns mediate the immune response in the noninfectious inflammatory response. Adult-onset Still's disease (AOSD) is a systemic inflammatory disorder involved in the dysregulation of innate immunity. We investigated the serum HMGB1 level in patients with AOSD and evaluated its clinical significance. Blood samples were collected from 40 patients with active AOSD and 40 healthy controls (HC). Of the patients with AOSD, follow-up samples were collected from 16 patients after a resolution of AOSD disease activity. Serum HMGB1 levels in patients with AOSD were higher than those of the HC (10.0 ± 5.85 vs. 5.15 ± 1.79 ng/mL, p < 0.001). Serum HMGB1 levels were found to be correlated with C-reactive protein (CRP) and the systemic score. The AOSD patient who had a sore throat showed a higher serum HMGB1 level than those patients who did not, and the patient with a skin rash had higher levels than the patients without. In addition, the serum HMGB1 levels were decreased after the resolution of disease activity in the AOSD patients who were followed up. The serum HMGB1 levels were elevated in AOSD patients compared to the HC and were correlated with both CRP and the systemic score. The HMGB1 levels were associated with skin rash and a sore throat in AOSD patients. After the resolution of disease activity, serum HMGB1 levels were found to have decreased.
26901532 Autoantibodies against the Second Extracellular Loop of M3R Do neither Induce nor Indicate 2016 OBJECTIVES: Anti-muscarinic acetylcholine type-3 receptor (anti-M3R) autoantibodies have been suggested to be pathogenic for primary Sjögren's syndrome (pSS), and the second extracellular loop of M3R is suspected to carry a disease-promoting epitope. In this study, we aimed to evaluate the pathogenicity of autoantibodies against peptides derived from the second extracellular loop of M3R in mice and to determine whether those autoantibodies could be used as biomarker for pSS. METHODS: BALB/c mice were immunized with modified linear or cyclic peptides of the second extracellular loop of M3R. The function of exocrine glands was evaluated by measuring the secretion of saliva and tears. The histological evaluations were performed by using H&E staining or direct immunofluorescence staining. Autoantibodies against linear or cyclic peptides of the second extracellular loop of M3R in human and mice were determined using ELISA. RESULTS: Immunization induced mice to produce autoantibodies against the linear or cyclic peptides of the second extracellular loop of M3R, and those autoantibodies could bind onto salivary glands. However, those mice showed neither impairment in the secretion of tears or saliva nor histological abnormality in the exocrine glands. Furthermore, passive transfer of the IgG isolated from the immunized mice into healthy mice did not induced the dysfunction of the exocrine glands. The prevalence of autoantibodies against the peptides of the second extracellular loop of M3R was low in pSS patients, and it did not differ significantly from that in healthy controls. CONCLUSIONS: Our results suggest that the autoantibodies against peptides of the second extracellular loop of M3R are not pathogenic in vivo and they are not suitable as biomarkers for pSS diagnosis.
26568188 Renal involvement in primary Sjögren syndrome. 2016 Feb Primary Sjögren syndrome (pSS) is an autoimmune disorder characterized by lymphoplasmacytic infiltration of the exocrine (salivary and lachrymal) glands that results in sicca symptoms (dryness of the eyes and mouth). Systemic complications can occur in pSS, but renal involvement is rare, affecting <10% patients. The most frequent form of nephropathy in pSS is tubulointerstitial nephritis (TIN), in which infiltration of the kidney by plasma cells is a key feature and shows similarity to the lymphoplasmacytic infiltration of the salivary glands. Electrolyte disturbances may occur in pSS, such as renal distal tubular acidosis, diabetes insipidus, Gitelman syndrome or Fanconi syndrome. Glomerular involvement is less frequently detected in patients with pSS, but usually takes the form of membranoproliferative glomerulonephritis secondary to cryoglobulinaemia. The renal prognosis in patients with pSS and TIN or glomerular disease is usually favourable, but the risk of chronic kidney disease remains high in patients with TIN. Appropriate screening must be performed at least once a year in patients with systemic pSS in order to facilitate the early detection of renal complications. In this Review we discuss the epidemiology, pathophysiology, differential diagnosis and treatment of renal disease in pSS.