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ID PMID Title PublicationDate abstract
29624878 Elastographic ultrasound: an additional image tool in Sjögren's syndrome. 2018 Jun AIM: To evaluate the stiffness of parotid and submandibular glands using elastography ultrasound and to correlate it with B-mode ultrasonographical, clinical and serological features, salivary profibrotic and inflammatory chemokines, and salivary gland fibrosis. METHODS: We performed B-mode and elastography ultrasound of major salivary glands of 26 patients with primary Sjögren's syndrome. We registered the shear wave velocity (SWV) and correlated it with the morphologic ultrasonographic changes assessed by the Hocevar scale. We assessed the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI), EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI), non-stimulated whole salivary flow rate (NSWSF), C3 and C4 levels, anti-Ro/La antibodies, salivary inflammatory (C-X-C motif ligand 13 [CXCL13], CXCL10, CXCL8, C-C motif ligand 2 [CCL2], interleukin 10 [IL-10] and IL-6) and pro-fibrotic (CXCL14, CCL28, tumor necrosis factor-related apoptosis-inducing ligand and transforming growth factor β) chemokines and cytokines and evaluated the presence of fibrosis in the minor salivary gland. RESULTS: Ninety-two percent of patients were women; mean age was 51.1 ± 11 years; median disease duration was 6.1 years; 92.3% had oral symptoms and 26.9% fibrosis. The median B-mode score was 22.2 points and the median SWV 2.5 m/s (τ = 0.53, P = 0.001). The SWV correlated with the NSWSF (τ = -0.53, P = 0.001), ESSDAI (τ = 0.31, P = 0.03), glandular ESDDAI domain (τ = 0.36, P = 0.02), C4 levels (τ = -0.32, P = 0.04), salivary CXCL13 (τ = 0.29, P = 0.03) and CXCL10 (τ = 0.30, P = 0.003), but not with age and fibrosis. CONCLUSION: WV correlated with the B-mode ultrasound score, systemic and glandular activity and in a large degree with CXCL10, an inflammatory chemokine, but not with fibrosis. An increased SWV might represent chronic glandular inflammation rather than fibrotic changes in these patients.
30132383 Effect of Bone Morphogenetic Protein 6 on Immunomodulatory Functions of Salivary Gland-Der 2018 Nov 15 Sjögren's syndrome (SS) is characterized by autoimmune activation and loss of function in the salivary glands. Recent studies reported that bone morphogenetic protein 6 (BMP6), which is a member of transforming growth factor beta (TGF-β) superfamily, was highly expressed in SS patients. To investigate the role of BMP6 in SS, we treated the salivary gland-derived mesenchymal stem cells (SGMSCs) with BMP6 and found that BMP6 could impair immunomodulatory properties of normal SGMSCs by downregulating the Prostaglandin E2 synthase through DNA-binding protein inhibitor-1. Neutralizing the BMP6 could significantly restore the SGMSC's immunoregulatory function in vitro and delay the SS disease activity in vivo. In conclusion, BMP6 could not only affect the secreting function of epithelial cells in the salivary gland but also influence the immunomodulatory properties of SGMSCs, which may trigger or enhance the autoimmune reflection in SS.
28124612 Unique Phenotypes and Functions of Follicular Helper T Cells and Regulatory T Cells in Sjà 2018 Sjogren's syndrome (SS) is a T cell-mediated autoimmune disease of the systemic exocrine glands, such as salivary and lacrimal glands. A variety of T-cell subpopulations maintain immune tolerance in the thymus and periphery through complex immune responses including cellular and humoral immunity. The T-cell subpopulations exhibiting abnormal or unique phenotypes and impaired functionality have been reported to play important roles in the cellular mechanisms of autoimmunity in SS patients and animal models of SS. In this review, we focused on follicular helper T cells related to antibody production and regulatory T cells to control immune tolerance in the pathogenesis of SS. The unique roles of these T-cell subpopulations in the process of the onset or development of SS have been demonstrated in this review of recent publications. The clinical application of these T-cell subpopulations will be helpful for the development of new techniques for diagnosis or treatment of SS in the future.
29605220 Lymphocytic focus score is positively related to airway and interstitial lung diseases in 2018 Apr OBJECTIVE: Although high-resolution computed tomography (HRCT) is useful for the characterization of minute morphological changes in the lungs, no study has investigated risk factors for lung involvement detected by HRCT in patients with Sjögren's syndrome with or without respiratory symptoms. The aim of the current study was to investigate risk factors for lung involvement in patients with primary Sjögren's syndrome detected by HRCT, with a particular focus on airway and interstitial lung diseases. METHODS: We performed a retrospective cohort study of patients with primary Sjögren's syndrome and investigated risk factors for lung involvement detected by HRCT. A total of 101 patients with primary Sjögren's syndrome with initial HRCT examinations were enrolled. RESULTS: Higher age, dry mouth, and higher labial gland biopsy focus scores (≥4) were risk factors for airway diseases (odds ratio [OR] 1.064 confidence interval [CI] 1.026-1.102, OR 8.795 CI 2.317-33.378 and OR 3.261 CI 1.100-9.675, respectively) in the multivariable analysis. Higher age, male sex, and higher labial gland biopsy focus scores (≥4) were risk factors for interstitial lung diseases (OR 1.078 CI 1.032-1.127, OR 12.178 CI 1.121-132.307 and OR 3.954 CI 1.423-10.987, respectively) in the multivariable analysis. The presence of anti-T-lymphotropic virus type 1 antibodies was significantly more common in patients with airway diseases. CONCLUSIONS: This study showed significant associations of labial gland biopsy focus scores and dry mouth with pulmonary manifestations in patients with primary Sjögren's syndrome. Focus scores as well as dry mouth may reflect lymphoproliferative activity in the lungs in patients with primary Sjögren's syndrome.
29534223 Impaired IRE1α/XBP-1 pathway associated to DNA methylation might contribute to salivary g 2018 Jun 1 OBJECTIVES: Labial salivary glands (LSGs) of SS patients show alterations related to endoplasmic reticulum stress. Glandular dysfunction could be partly the consequence of an altered inositol-requiring enzyme 1α (IRE1α)/X box-binding protein 1 (XBP-1) signalling pathway of the unfolded protein response, which then regulates genes involved in biogenesis of the secretory machinery. This study aimed to determine the expression, promoter methylation and localization of the IRE1α/XBP-1 pathway components in LSGs of SS patients and also their expression induced by IFN-γ in vitro. METHODS: IRE1α, XBP-1 and glucose-regulated protein 78 (GRP78) mRNA and protein levels were measured by qPCR and western blot, respectively, in LSGs of SS patients (n = 47) and control subjects (n = 37). Methylation of promoters was evaluated by methylation-sensitive high resolution melting, localization was analysed by immunofluorescence and induction of the IRE1α/XBP-1 pathway components by IFN-γ was evaluated in 3D acini. RESULTS: A significant decrease of IRE1α, XBP-1u, XBP-1s, total XBP-1 and GRP78 mRNAs was observed in LSGs of SS patients, which was correlated with increased methylation levels of their respective promoters, and consistently the protein levels for IRE1α, XBP-1s and GRP78 were observed to decrease. IFN-γ decreased the mRNA and protein levels of XBP-1s, IRE1α and GRP78, and increased methylation of their promoters. Significant correlations were also found between IRE1α/XBP-1 pathway components and clinical parameters. CONCLUSION: Decreased mRNA levels for IRE1α, XBP-1 and GRP78 can be partially explained by hypermethylation of their promoters and is consistent with chronic endoplasmic reticulum stress, which may explain the glandular dysfunction observed in LSGs of SS patients. Additionally, glandular stress signals, including IFN-γ, could modulate the expression of the IRE1α/XBP-1 pathway components.
29381843 Efficacy of Epratuzumab, an Anti-CD22 Monoclonal IgG Antibody, in Systemic Lupus Erythemat 2018 May OBJECTIVE: EMBODY 1 (ClinicalTrials.gov identifier: NCT01262365) and EMBODY 2 (ClinicalTrials.gov identifier: NCT01261793) investigated the efficacy and safety of epratuzumab, a CD22-targeted humanized monoclonal IgG antibody, in patients with systemic lupus erythematosus (SLE). The studies showed no significant difference from placebo in primary or secondary clinical outcome measures but did demonstrate B cell-specific immunologic activity. The aim of this post hoc analysis was to determine whether epratuzumab had a different clinical efficacy profile in SLE patients with versus those without an associated diagnosis of Sjögren's syndrome (SS). METHODS: The efficacy and safety of epratuzumab were compared between 2 patient subpopulations randomized in EMBODY 1 and 2: SLE patients with and those without a diagnosis of associated SS. British Isles Lupus Assessment Group (BILAG) total score, BILAG-based Combined Lupus Assessment (BICLA) clinical response to treatment, biologic markers (including B cells, IgG, IgM, and IgA), and safety were assessed. RESULTS: A total of 1,584 patients were randomized in the EMBODY 1 and EMBODY 2 trials; 113 patients were anti-SSA positive and had a diagnosis of associated SS, and 1,375 patients (86.8%) had no diagnosis of associated SS (918 patients were randomized to receive epratuzumab and 457 to receive placebo). For patients with associated SS, but not those without associated SS, a higher proportion of patients receiving epratuzumab achieved a BICLA response and a reduction from baseline in BILAG total score. B cell reduction was faster in patients with associated SS. The sensitivity of B cells to epratuzumab as measured by the mean concentration producing 50% of the maximum B cell count depletion was lower for patients with associated SS (9.5 μg/ml) versus the total EMBODY population (87.1 μg/ml). No difference in the frequency of adverse events in those receiving placebo was reported. CONCLUSION: Patients with SLE and associated SS treated with epratuzumab showed improvement in SLE disease activity, which was associated with bioactivity, such as decreases in B cell number and IgM level.
33655144 A Novel Treatment of Acne Fulminans with Adalimumab: A Case Report. 2018 Sep 26 Acne fulminans (AF) is a rare and highly inflammatory severe form of acne most commonly seen in adolescent males. Unlike acne vulgaris, AF presents with associated systemic manifestations including, but not limited to, malaise, myalgia, arthralgia, fever, anorexia, and weight loss. It is often an extremely painful condition of sudden onset and can occur years after mild or moderate acne vulgaris. While the inciting agent for this condition has been postulated to be an explosive hypersensitivity reaction to the bacterium Propionobacterium acnes, increased androgens, namely testosterone, have also been reported to play a role in the pathogenesis of this disease process. Additionally, environmental triggers such as air pollution and exposure to halogenated hydrocarbons during occupational activities in enclosed, high temperature settings have been identified as possible etiologies or exacerbating factors. AF is primarily a clinical diagnosis. Isotretinoin, in combination with systemic steroids, are generally the treatments of choice for this disease entity. A Caucasian male in his early 40's presented to the authors' clinic with a chief complaint of painful acneiform nodules, cysts, papules, pustules, and abscesses on his back, chest, neck, shoulders, upper arms, and thighs for several months. This case report demonstrates a refractory case of AF with significant clinical improvement after six weeks of topical treatment with subcutaneous adalimumab in combination with oral doxycycline. This case provides evidence supporting the role of Adalimumab in the treatment of AF in addition to the other inflammatory conditions currently FDA approved for treatment with this tumor-necrosis factor (TNF) alpha inhibitor. These conditions include plaque psoriasis, Crohn's disease, hidradenitis suppurativa, psoriatic arthritis, and rheumatoid arthritis.
30143962 Correction to: Development and application of a questionnaire to assess patient beliefs in 2018 Oct The original version of this article was revised due to a retrospective Open Access order.
31316589 Scoping review: Diagnosis and management of periprosthetic joint infection in elbow arthro 2019 Aug BACKGROUND: Total elbow arthroplasty is an effective treatment for patients with painful elbow arthritis. Infection can be a serious complication. The aim of this scoping review was to document the available evidence on periprosthetic elbow infection. METHODS: A search of Medline, Embase and PubMed was performed; two authors screened results independently. Systematic reviews, randomised controlled trials, cohort studies, case-control studies and case series including periprosthetic elbow infection were eligible. RESULTS: A total of 46 studies were included. The median rate of periprosthetic elbow infection reported from recent published studies is 3.3%. The most commonly identified causative organisms are Staphylococcus aureus and Staphylococcus epidermidis. Risk factors include younger age, rheumatoid arthritis, obesity, previous surgery or infection to the elbow, and postoperative wound complications. Debridement, antibiotics and implant retention results in implant survival rates of 50-90%. Two-stage revision results in improved functional outcome scores, but with recurrent infection rates of 12-28%. CONCLUSIONS: Total elbow arthroplasty carries a higher risk of infection when compared to other major joint replacements. The current body of literature is limited and is almost exclusively low volume retrospective case series. The best management of periprosthetic elbow infection is difficult to determine, but two-stage revision appears to be the gold standard.
30025850 Comparative study of anti-VEGF Ranibizumab and Interleukin-6 receptor antagonist Tocilizum 2018 Oct 1 Although the precise etiology of Rheumatoid arthritis (RA) remains obscure, heightened immune response is thought to play a vital role in provoking joint inflammation and bone erosion. This study aims at comparatively evaluating the effects of two monoclonal antibodies Ranibizumab (RANI) as anti-VEGF antibody and Tocilizumab (TCZ) as interleukin-6 receptor (IL-6R) antagonist, against adjuvant induced arthritis in rats. CFA-induced arthritic rats were treated for three consecutive weeks with Methotrexate (MTX), TCZ and RANI monotherapy. Clinical assessment of RA, bone erosion, inflammatory, angiogenic and apoptotic markers were determined to assess the anti-arthritic effect. Liver enzymes and histopathological examination of liver and spleen were assessed to evaluate the toxicity profile of the tested therapeutic agents. MTX, TCZ and RANI monotherapy significantly enhanced the anti-arthritic parameters in comparison with the Complete Freund's Adjuvant (CFA)-induced arthritic rats through significant reduction of ankle and paw swelling. Also, they significantly reduced inflammatory, angiogenic and apoptotic markers. Importantly, Ranibizumab showed better effect than the standard anti-rheumatic drugs Methotrexate (MTX) or Tocilizumab (TCZ) in bone protection and cartilage health; hence proves to be a promising new therapeutic agent for RA.
29780656 Primary Leiomyosarcoma of the Colon: A Report of Two Cases, Review of the Literature, and 2018 Primary leiomyosarcomas (LMS) of the colon are rare and aggressive neoplasms and have been infrequently reported in the literature. These tumors are more aggressive and have poorer prognoses than adenocarcinoma of the colon and are often mistaken as such on initial evaluation. While the former has a clear association with inflammatory bowel disease (IBD), this correlation is not known to exist with LMS and IBD. Nor is there a known link between LMS and the immunosuppression for IBD, despite the known association between malignancy and immunosuppression for other diseases. Due to the low prevalence of this disease entity, there is limited knowledge and literature on the approach to diagnosing and treating these neoplasms, especially in the setting of the aforementioned comorbidities. Here, we describe two cases of this rare entity, presenting in two different circumstances: one in the setting of immunosuppression for IBD and arthritis, with a synchronous urothelial carcinoma, and the second appearing as the source of an acute abdomen. Both diagnoses were established following pathologic analysis.
29112801 Value of the Routine Assessment of Patient Index Data 3 in Patients With Psoriatic Arthrit 2018 Aug OBJECTIVE: To analyze the Routine Assessment of Patient Index Data 3 (RAPID3), a patient-reported, composite index, designed initially for feasibility in clinical care. RAPID3 was developed in rheumatoid arthritis, but has been found useful in many rheumatic diseases. We analyzed RAPID3 in patients with psoriatic arthritis (PsA). METHODS: Post hoc analyses were performed on 2 independent data sets, the Tight Control of Psoriatic Arthritis (TICOPA) clinical trial, and the Long-Term Outcome in Psoriatic Arthritis Study (LOPAS II), an observational cohort. RAPID3 (range 0-30) is the total of three 0-10 scores for the Health Assessment Questionnaire disability index (recalculated from 0-3), pain visual analog scale (VAS), and global VAS. RAPID3 scores were compared to the Psoriatic Arthritis Disease Activity Score (PASDAS), the Disease Activity in Psoriatic Arthritis (DAPSA), and other available clinical measures, according to Spearman's correlation coefficients, standardized response mean, SEM, smallest detectible difference, minimally important difference (in patients who improved), and receiver operating characteristic curves. RAPID3 remission was compared to criteria for both standard minimal disease activity (MDA) and very low disease activity (VLDA). RESULTS: RAPID3 was correlated significantly with PASDAS in TICOPA (r = 0.79, P < 0.01) and with DAPSA in LOPAS II (ρ = 0.59, P < 0.01), and with most other measures in both data sets. RAPID3 discriminated between tight control and standard care in TICOPA at 48 weeks at levels comparable to DAPSA and the PASDAS (P < 0.01). RAPID3 remission discriminated treatment groups in TICOPA intermediate between MDA and VLDA criteria. CONCLUSION: RAPID3 appears comparably informative to PASDAS and DAPSA in PsA, with greater feasibility for routine clinical care.
30008454 Tongue Atrophy in Sjögren Syndrome Patients with Mucosa-associated Lymphoid Tissue Lympho 2018 Nov OBJECTIVE: Primary Sjögren syndrome (pSS), an autoimmune epithelitis, bears the risk of evolving to non-Hodgkin lymphoma and most frequently to the mucosa-associated lymphoid tissue (MALT) subtype. Based on the observation that pSS patients with MALT present a more atrophic and more intensely fissured tongue, we aimed to semiquantify severity of tongue atrophy and clinically assess lingual appearance in pSS patients with and without MALT, and investigate whether tongue atrophy and fissured appearance could serve as clinical indicators/signs of MALT. METHODS: A blinded complete oral examination was performed in pSS patients with and without MALT. Tongue atrophy was scored using a semiquantified atrophy score. Clinical and laboratory variables were recorded for all patients. RESULTS: After excluding pSS patients with oral candidiasis, iron deficiency, and megaloblastic anemia, 19 pSS patients with salivary MALT were matched 1:3 for age, sex, and disease duration with 57 pSS patients without MALT. The pSS-MALT patients had increased prevalence of salivary gland enlargement, lymphadenopathy, monoclonal gammopathy, rheumatoid factor positivity, higher focus and Tarpley scores in the minor salivary gland biopsy, and hyposalivation, compared to the pSS non-MALT patients. A significantly higher prevalence of tongue atrophy (68% vs 30%, p = 0.006) and fissured tongue (89% vs 33%, p < 0.001) was observed in the former group. Multivariate analysis showed that fissured tongue appearance, hyposalivation, and lymphadenopathy associate independently with salivary MALT in pSS. CONCLUSION: These results suggest that pSS patients with lymphoid malignancy exhibit a more atrophic and more fissured tongue. This particular clinical tongue appearance can serve as an additional clinical sign for salivary MALT lymphoma in pSS patients.
29445174 A spatial gradient of bacterial diversity in the human oral cavity shaped by salivary flow 2018 Feb 14 Spatial and temporal patterns in microbial communities provide insights into the forces that shape them, their functions and roles in health and disease. Here, we used spatial and ecological statistics to analyze the role that saliva plays in structuring bacterial communities of the human mouth using >9000 dental and mucosal samples. We show that regardless of tissue type (teeth, alveolar mucosa, keratinized gingiva, or buccal mucosa), surface-associated bacterial communities vary along an ecological gradient from the front to the back of the mouth, and that on exposed tooth surfaces, the gradient is pronounced on lingual compared to buccal surfaces. Furthermore, our data suggest that this gradient is attenuated in individuals with low salivary flow due to Sjögren's syndrome. Taken together, our findings imply that salivary flow influences the spatial organization of microbial communities and that biogeographical patterns may be useful for understanding host physiological processes and for predicting disease.
28928271 The value of (18)F-FDG-PET/CT in identifying the cause of fever of unknown origin (FUO) an 2018 Jan BACKGROUND: Fever of unknown origin (FUO) and inflammation of unknown origin (IUO) are diagnostically challenging conditions. Diagnosis of underlying disease may be improved by (18)F-fluorodesoxyglucose positron emission tomography ((18)F-FDG-PET). METHODS: Prospective study to test diagnostic utility of (18)F-FDG-PET/CT in a large cohort of patients with FUO or IUO and to define parameters that increase the likelihood of diagnostic (18)F-FDG-PET/CT. Patients with FUO or IUO received (18)F-FDG-PET/CT scanning in addition to standard diagnostic work-up. (18)F-FDG-PET/CT results were classified as helpful or non-helpful in establishing final diagnosis. Binary logistic regression was used to identify clinical parameters associated with a diagnostic (18)F-FDG-PET/CT. RESULTS: 240 patients were enrolled, 72 with FUO, 142 with IUO and 26 had FUO or IUO previously (exFUO/IUO). Diagnosis was established in 190 patients (79.2%). The leading diagnoses were adult-onset Still's disease (15.3%) in the FUO group, large vessel vasculitis (21.1%) and polymyalgia rheumatica (18.3%) in the IUO group and IgG(4)-related disease (15.4%) in the exFUO/IUO group. In 136 patients (56.7% of all patients and 71.6% of patients with a diagnosis), (18)F-FDG-PET/CT was positive and helpful in finding the diagnosis. Predictive markers for a diagnostic (18)F-FDG-PET/CT were age over 50 years (p=0.019), C-reactive protein (CRP) level over 30 mg/L (p=0.002) and absence of fever (p=0.001). CONCLUSION: (18)F-FDG-PET/CT scanning is helpful in ascertaining the correct diagnosis in more than 50% of the cases presenting with FUO and IUO. Absence of intermittent fever, higher age and elevated CRP level increase the likelihood for a diagnostic (18)F-FDG-PET/CT.
28765121 Novel therapies for immune-mediated inflammatory diseases: What can we learn from their us 2018 Feb The past three decades have witnessed remarkable advances in our ability to target specific elements of the immune and inflammatory response, fuelled by advances in both biotechnology and disease knowledge. As well as providing superior treatments for immune-mediated inflammatory diseases (IMIDs), such therapies also offer unrivalled opportunities to study the underlying immunopathological basis of these conditions.In this review, we explore recent approaches to the treatment of IMIDs and the insights to pathobiology that they provide. We review novel biologic agents targeting the T-helper 17 axis, including therapies directed towards interleukin (IL)-17 (secukinumab, ixekizumab, bimekizumab), IL-17R (brodalumab), IL-12/23p40 (ustekinumab, briakinumab) and IL-23p19 (guselkumab, tildrakizumab, brazikumab, risankizumab, mirikizumab). We also present an overview of biologics active against type I and II interferons, including sifalumumab, rontalizumab, anifrolumab and fontolizumab. Emerging strategies to interfere with cellular adhesion processes involved in lymphocyte recruitment are discussed, including both integrin blockade (natalizumab, vedolizumab, etrolizumab) and sphingosine-1-phosphate receptor inhibition (fingolimod, ozanimod). We summarise the development and recent application of Janus kinase (JAK) inhibitors in the treatment of IMIDs, including first-generation pan-JAK inhibitors (tofacitinib, baricitinib, ruxolitinib, peficitinib) and second-generation selective JAK inhibitors (decernotinib, filgotinib, upadacitinib). New biologics targeting B-cells (including ocrelizumab, veltuzumab, tabalumab and atacicept) and the development of novel strategies for regulatory T-cell modulation (including low-dose IL-2 therapy and Tregitopes) are also discussed. Finally, we explore recent biotechnological advances such as the development of bispecific antibodies (ABT-122, COVA322), and their application to the treatment of IMIDs.
29443033 A Method for the Measurement of Salivary Gland Function in Mice. 2018 Jan 25 Patients with Sjögren's syndrome, an autoimmune disease affecting the exocrine glands, develop salivary gland inflammation and have reduced saliva production. Similarly, saliva production is severely compromised in patients receiving radiation treatment for head and neck cancers. Rodent models, developed to mimic these clinical conditions, facilitate an understanding of the disease pathogenesis and allow for the development of new therapeutic strategies. Therefore, the ability to accurately, reproducibly, and repeatedly measure salivary gland function in animal models is critical. Building on procedures previously described in the literature, a method was developed that meets these criteria and was used to evaluate salivary gland function in mice. An additional advantage of this new method is that it is easily mastered, and has little inter-operator variation. Salivary gland function is evaluated as the amount (weight or volume) or rate (mL/min) of saliva produced in response to pilocarpine stimulation. The collected saliva is a good source for the analyses of protein content, immunoglobulin concentrations, and other biomolecules.
29378778 Deficiency in T follicular regulatory cells promotes autoimmunity. 2018 Mar 5 T follicular regulatory (Tfr) cells are a new subset of regulatory T (T reg) cells localized in the germinal center to limit the humoral response. Until now, the physiological function of Tfr cells has been largely unknown. In this study, we developed a Bcl6(fl/fl)Foxp3Cre mouse to analyze the function of Tfr cells in immune and autoimmune responses. These mice exhibited enhanced immunity to influenza virus; moreover, Bcl6(fl/fl)Foxp3Cre/Cre mice developed late-onset spontaneous autoimmune diseases, affecting the salivary glands with lymphocyte infiltration and antibody deposition. In a mouse experimental Sjögren's syndrome model, ablation of Bcl6 in T reg cells greatly enhanced disease development. Conversely, Bcl6(fl/fl)Cd4Cre mice were protected in the model. Thus, our study indicates that Tfr cells control autoimmune diseases and can be targeted in infectious and autoimmune disease.
28904255 Predictors of Favorable Responses to Immunosuppressive Treatment in Pulmonary Arterial Hyp 2018 Jan 25 BACKGROUND: The potential efficacy of immunosuppressive (IS) treatment has been reported in patients with pulmonary arterial hypertension (PAH) associated with connective tissue disease (CTD), but its positioning in the treatment algorithm remains uncertain. The aim of this study was to identify predictors of favorable responses to first-line IS treatment.Methods and Results:This single-center retrospective study included 30 patients with PAH accompanied by systemic lupus erythematosus (SLE), mixed CTD (MCTD), or primary Sjögren's syndrome (SS) who received first-line IS treatment alone or in combination with pulmonary vasodilators. When short-term treatment response was defined as an improvement in World Health Organization functional class at 3 months, 16 patients (53%) were short-term responders. Simultaneous diagnosis of PAH and CTD, and the use of immunosuppressants, especially intravenous cyclophosphamide, in addition to glucocorticoids were identified as independent predictors of a short-term response (P=0.004 and 0.0002, respectively). Cumulative rates free of PAH-related death were better in short-term responders than non-responders (P=0.04), and were best in patients with a simultaneous diagnosis of PAH and CTD who were treated initially with a combination of glucocorticoids and immunosuppressants. CONCLUSIONS: Patients with a simultaneous diagnosis of PAH and CTD, including SLE, MCTD, and primary SS, should receive intensive IS treatment regimens to achieve better short- and long-term outcomes.
28529117 New Markers for Adult-Onset Still's Disease. 2018 May Adult-onset Still's disease (AOSD) is a rare systemic auto-inflammatory disorder (SAID). Although the pathogenesis of the disease is complex and far from being fully understood, recent progresses in pathophysiological knowledge have paved the way to new diagnostic approaches. Indeed, AOSD diagnosis can be a real challenge, owing to its infrequency, and to the lack of specificity of the principal clinical features (high fever, arthralgia or arthritis, skin rash) and laboratory findings (elevated acute phase reactants, hyperleukocytosis≥10,000 cells/mm(3) with neutrophils≥80%). None of these manifestations is disease-specific, so clinicians must first rule out neoplastic, infectious or inflammatory conditions. Besides these diagnostic difficulties, several other challenges remain. AOSD is very heterogeneous in terms of clinical presentation, evolution and severity. Thus, new biomarkers are required to assess: (i) disease activity; (ii) disease severity (through the identification of patients at risk of severe organ failure, and eventually of life-threatening complications, such as reactive haemophagocytic lymphohistiocytosis); (iii) disease evolution (which can be monophasic, relapsing, or progressive, with either systemic inflammation or chronic erosive arthritis); (iv) and treatment efficacy. The identification of new markers can only be done through a better understanding of the pathogenesis of the disease. After a short focus on the current AOSD pathophysiological knowledge, this article reviews the main biomarkers that have been proposed in the literature over the last few years.