A novel mutation of indoleamine 2,3-dioxygenase 1 causes a rapid proteasomal degradation and compromises protein function.
Abstract Indoleamine 2,3-dioxygenase 1 (IDO1) - the enzyme catalyzing the rate-limiting step of tryptophan catabolism along the kynurenine pathway - belongs to the class of inhibitory immune checkpoint molecules. Such regulators of the immune system are crucial for maintaining self-tolerance and thus, when properly working, preventing autoimmunity. A dysfunctional IDO1 has recently been associated with a specific single nucleotide polymorphism (SNP) and with the occurrence of autoimmune diabetes and multiple sclerosis. Many genetic alterations of IDO1 have been proposed being related with dysimmune disorders. Howe...
Source: Journal of Autoimmunity - June 27, 2020 Category: Allergy & Immunology Authors: Mondanelli G, Di Battista V, Pellanera F, Mammoli A, Macchiarulo A, Gargaro M, Mavridou E, Matteucci C, Ruggeri L, Orabona C, Volpi C, Grohmann U, Mecucci C Tags: J Autoimmun Source Type: research

Primaquine elicits Foxp3+ regulatory T cells with a superior ability to limit CNS autoimmune inflammation.
Abstract Multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) are neuroinflammatory conditions where inflammatory CD4+ T cells play a major role. Forkhead box P3 (Foxp3)+ regulatory T (Treg) cells suppress inflammation and an increase in their numbers and activity is beneficial for MS and EAE. However, studies have shown that Treg cells can transdifferentiate to pathogenic Th17 cells under inflammatory conditions. Drugs that stimulate Treg cell induction and their resistance to inflammatory stimuli are necessary to develop effective therapies to treat MS. Here, we show that primaquine (...
Source: Journal of Autoimmunity - June 25, 2020 Category: Allergy & Immunology Authors: Thome R, Casella G, Lotfi N, Ishikawa LWL, Wang Q, Ciric B, Zhang GX, Rostami A Tags: J Autoimmun Source Type: research

Autoimmunity to neuroretina in the concurrent absence of IFN- γ and IL-17A is mediated by a GM-CSF-driven eosinophilic inflammation.
Autoimmunity to neuroretina in the concurrent absence of IFN-γ and IL-17A is mediated by a GM-CSF-driven eosinophilic inflammation. J Autoimmun. 2020 Jun 24;:102507 Authors: Bing SJ, Silver PB, Jittayasothorn Y, Mattapallil MJ, Chan CC, Horai R, Caspi RR Abstract IFN-γ and IL-17A can each elicit ocular autoimmunity independently of the other. Since absence of IFN-γ or IL-17A individually failed to abolish pathology of experimental autoimmune uveitis (EAU), we examined EAU development in the absence of both these cytokines. Ifng-/-Il17a-/- mice were fully susceptible to EAU with a cha...
Source: Journal of Autoimmunity - June 24, 2020 Category: Allergy & Immunology Authors: Bing SJ, Silver PB, Jittayasothorn Y, Mattapallil MJ, Chan CC, Horai R, Caspi RR Tags: J Autoimmun Source Type: research

Comparison of conventional immunosuppressive drugs versus anti-TNF- α agents in non-infectious non-anterior uveitis.
CONCLUSION: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency. PMID: 32586650 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 22, 2020 Category: Allergy & Immunology Authors: Leclercq M, Langlois V, Girszyn N, Le Besnerais M, Benhamou Y, Levesque H, Muraine M, Gueudry J Tags: J Autoimmun Source Type: research

VISTA deficiency protects from immune complex-mediated glomerulonephritis by inhibiting neutrophil activation.
on MG Abstract V-type immunoglobulin domain-containing suppressor of T-cell activation (VISTA) is a negative checkpoint regulator of T cells. We assessed VISTA deficient mice in the murine nephrotoxic nephritis models of acute and chronic immune-complex mediated glomerulonephritis. We show that VISTA deficiency protects from crescentic glomerulonephritis, with no effect on the nephritogenic adaptive immune response. The early neutrophil influx was unaffected but proteinuria was reduced suggesting a reduction in neutrophil activation. In vivo, there was reduced neutrophil degranulation in VISTA deficienct mice and,...
Source: Journal of Autoimmunity - June 22, 2020 Category: Allergy & Immunology Authors: Tham EL, Freeley SJ, Bearder S, Barros FF, Cragg MS, Mócsai A, Robson MG Tags: J Autoimmun Source Type: research

LAG3 (CD223) and autoimmunity: Emerging evidence.
Abstract Immune checkpoint molecules play pivotal roles in maintaining the immune homeostasis. Targeting these molecules, such as the classical Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) and Programmed Cell Death Protein 1 (PD1), achieves great success in treating cancers. However, not all the patients respond well. This urges the immunologists to identify novel immune checkpoint molecules. Lymphocyte activation gene-3 (LAG3; CD223) is a newly identified inhibitory receptor. It is expressed on a variety of immune cells, including CD4+ T cells, CD8+ T cells, Tregs, B cells, and NK cells. Its unique intracellular doma...
Source: Journal of Autoimmunity - June 20, 2020 Category: Allergy & Immunology Authors: Hu S, Liu X, Li T, Li Z, Hu F Tags: J Autoimmun Source Type: research

Alterations in corneal biomechanics underlie early stages of autoimmune-mediated dry eye disease.
Abstract Autoimmune-mediated dry eye disease is a pathological feature of multiple disorders including Sjögren's syndrome, lupus and rheumatoid arthritis that has a life-long, detrimental impact on vision and overall quality of life. Although late stage disease outcomes such as epithelial barrier dysfunction, reduced corneal innervation and chronic inflammation have been well characterized in both human patients and mouse models, there is little to no understanding of early pathological processes. Moreover, the mechanisms underlying the loss of cornea homeostasis and disease progression are unknown. Here, we ...
Source: Journal of Autoimmunity - June 18, 2020 Category: Allergy & Immunology Authors: Efraim Y, Chen FYT, Stashko C, Cheong KN, Gaylord E, McNamara N, Knox SM Tags: J Autoimmun Source Type: research

Human gingiva-derived mesenchymal stem cells are therapeutic in lupus nephritis through targeting of CD39-CD73 signaling pathway.
Abstract Cell specific and cytokine targeted therapeutics have underperformed in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) have emerged as a novel therapy to address the dysregulation in autoimmune diseases but also have limitations. Human gingiva derived MSCs (GMSCs) are superior in regulating immune responses. Here, we demonstrate that the adoptive transfer of GMSCs homes to and maintains in the kidney and has a robust therapeutic effect in a spontaneous lupus nephritis model. Specifically, GMSCs limits the development of autoantibodies as well as proteinuria, decreases the frequency of p...
Source: Journal of Autoimmunity - June 18, 2020 Category: Allergy & Immunology Authors: Dang J, Xu Z, Xu A, Liu Y, Fu Q, Wang J, Huang F, Zheng Y, Qi G, Sun B, Bellanti JA, Kandalam U, Emam HA, Jarjour W, Zheng SG Tags: J Autoimmun Source Type: research

Autoinflammatory and autoimmune conditions at the crossroad of COVID-19.
C, Anaya JM Abstract Coronavirus disease 2019 (COVID-19) has been categorized as evolving in overlapping phases. First, there is a viral phase that may well be asymptomatic or mild in the majority, perhaps 80% of patients. The pathophysiological mechanisms resulting in minimal disease in this initial phase are not well known. In the remaining 20% of cases, the disease may become severe and/or critical. In most patients of this latter group, there is a phase characterized by the hyperresponsiveness of the immune system. A third phase corresponds to a state of hypercoagulability. Finally, in the fourth stage organ i...
Source: Journal of Autoimmunity - June 16, 2020 Category: Allergy & Immunology Authors: Rodríguez Y, Novelli L, Rojas M, De Santis M, Acosta-Ampudia Y, Monsalve DM, Ramírez-Santana C, Costanzo A, Ridgway WM, Ansari AA, Gershwin ME, Selmi C, Anaya JM Tags: J Autoimmun Source Type: research

Glycomic analysis of antibody indicates distinctive glycosylation profile in patients with autoimmune cholangitis.
Abstract Glycosylation of antibodies, particularly in the Fc domain, critically modulate the ability of antibodies to bind to FcRs, maintaining immune quiescence to achieve a finely orchestrated immune response. The removal of sialic acid and galactose residues dramatically alters the physiological function of IgGs, and alterations of Ig glycosylation have been associated with several autoimmune disorders. However, Ig glycosylation has not been extensively studied in autoimmune cholangitis. We applied triple quadruple mass spectroscopy with subsequent multiple reaction monitoring to elucidate the profile, composit...
Source: Journal of Autoimmunity - June 13, 2020 Category: Allergy & Immunology Authors: Zhou X, Kailemia MJ, Sun Y, Shuai Z, Yang GX, Dhaliwal S, Cristoferi L, Leung PSC, Invernizzi P, Bowlus CL, Lebrilla CB, Ansari AA, Ridgway WM, Zhang W, Gershwin ME Tags: J Autoimmun Source Type: research

Correlation of the levels of DNA-binding inhibitor Id3 and regulatory T cells with SLE disease severity.
In this study, we systematically analyzed Id transcription in naïve, memory CD4 cells and regulatory T cells in peripheral blood mononuclear cells (PBMCs) in patients with active or inactive SLE. In parallel, Treg subsets in PBMCs were analyzed using different strategies. Id expression levels were correlated with Treg numbers as well as clinical indicators. We found that Id genes expressed in human peripheral CD4 cells were mainly Id2 and Id3. Id3 levels were significantly elevated in CD4+CD25hi T cells of patients with active SLE. Likewise, Id3 levels were positively correlated with increased CD4+FoxP3+ and CD4+Helio...
Source: Journal of Autoimmunity - June 11, 2020 Category: Allergy & Immunology Authors: Liu C, Yu S, Jin R, Long Y, Lu S, Song Y, Sun X, Sun XH, Zhang Y Tags: J Autoimmun Source Type: research

Are lupus animal models useful for understanding and developing new therapies for human SLE?
Abstract Systemic lupus erythematosus is a systemic autoimmune disease driven by a complex combination of genetic, environmental, and other immunoregulatory factors. The development of targeted therapies is complicated by heterogeneous clinical manifestations, varying organ involvement, and toxicity. Despite advances in understanding the mechanisms contributing to SLE, only one biologic drug, belimumab, is FDA-approved. The identification and development of potential therapies have largely been driven by studies in lupus animal models. Therefore, direct comparison of both the therapeutic and immunological findings...
Source: Journal of Autoimmunity - June 10, 2020 Category: Allergy & Immunology Authors: Moore E, Putterman C Tags: J Autoimmun Source Type: research

SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.
CONCLUSIONS: COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high. PMID: 32527675 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - June 8, 2020 Category: Allergy & Immunology Authors: Zen M, Fuzzi E, Astorri D, Saccon F, Padoan R, Ienna L, Cozzi G, Depascale R, Zanatta E, Gasparotto M, Benvenuti F, Bindoli S, Gatto M, Felicetti M, Ortolan A, Campaniello D, Larosa M, Lorenzin M, Ramonda R, Sfriso P, Schiavon F, Iaccarino L, Doria A Tags: J Autoimmun Source Type: research

CD137 / CD137 ligand signalling regulates the immune balance: A potential target for novel immunotherapy of autoimmune diseases.
Abstract CD137 (TNFRSF9, 4-1BB) is a potent co-stimulatory molecule of the tumour necrosis factor receptor superfamily (TNFRSF) that is expressed by activated T cells. CD137/CD137 ligand (CD137L) signalling primarily induces a potent cell-mediated immune response, while signalling of cell surface-expressed CD137L into antigen presenting cells enhances their activation, differentiation and migratory capacity. Studies have shown that bidirectional CD137/CD137L signalling plays an important role in the pathogenesis of autoimmune diseases. This review discusses the mechanisms how CD137/CD137L signalling contributes to...
Source: Journal of Autoimmunity - June 4, 2020 Category: Allergy & Immunology Authors: Wong HY, Schwarz H Tags: J Autoimmun Source Type: research

MuSK antibodies, lessons learned from poly- and monoclonality.
Abstract Muscle-specific kinase (MuSK) plays a critical role in establishing and maintaining neuromuscular synapses. Antibodies derived from immunizing animals with MuSK were important tools to help detect MuSK and its activity. The role of antibodies in MuSK-related research got an extra dimension when autoantibodies to MuSK were found to cause myasthenia gravis (MG) in 2001. Active immunization with MuSK or passive transfer of polyclonal purified IgG(4) fractions from patients reproduced myasthenic muscle weakness in a range of animal models. Polyclonal patient-purified autoantibodies were furthermore found to b...
Source: Journal of Autoimmunity - June 3, 2020 Category: Allergy & Immunology Authors: Vergoossen DLE, Augustinus R, Huijbers MG Tags: J Autoimmun Source Type: research

Tolerization of recent thymic emigrants is required to prevent RBC-specific autoimmunity.
Abstract Autoimmune hemolytic anemia (AIHA) leads to accelerated destruction of autologous red blood cells (RBCs) by autoantibodies. AIHA is a severe and sometimes fatal disease. While there are several therapeutic strategies available, there are currently no licensed treatments for AIHA and few therapeutics result in treatment-free durable remission. The etiology of primary AIHA is unknown; however, secondary AIHA occurs concurrently with lymphoproliferative disorders and infections. Additionally, AIHA is the second most common manifestation of primary immunodeficiency disorders and has been described as a side e...
Source: Journal of Autoimmunity - June 2, 2020 Category: Allergy & Immunology Authors: Wong ASL, Gruber DR, Richards AL, Sheldon K, Qiu A, Hay A, Hudson KE Tags: J Autoimmun Source Type: research

Systemic lupus erythematosus, endothelial progenitor cells and intracellular Ca2+ signaling: A novel approach for an old disease.
cia F Abstract Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease featured by an increased cardiovascular risk that may lead to premature patient's death. It has been demonstrated that SLE patients suffer from early onset endothelial dysfunction which is due to the impairment of endogenous vascular repair mechanisms. Vascular integrity and homeostasis are maintained by endothelial progenitor cells (EPCs), which are mobilized in response to endothelial injury to replace damaged endothelial cells. Two main EPCs subpopulations exist in peripheral blood: endothelial colony forming cells (ECFCs), w...
Source: Journal of Autoimmunity - May 29, 2020 Category: Allergy & Immunology Authors: Komici K, Faris P, Negri S, Rosti V, García-Carrasco M, Mendoza-Pinto C, Berra-Romani R, Cervera R, Guerra G, Moccia F Tags: J Autoimmun Source Type: research

Homocysteinylated alpha 1 antitrypsin as an antigenic target of autoantibodies in seronegative rheumatoid arthritis patients.
In conclusion, anti-HATA can be considered potential biomarkers for RA, also in the SN forms. The discovery of novel autoAbs targeting specific autoantigens can represent higher clinic significance for all RA patients' population. PMID: 32473759 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - May 27, 2020 Category: Allergy & Immunology Authors: Colasanti T, Sabatinelli D, Mancone C, Giorgi A, Pecani A, Spinelli FR, Di Giamberardino A, Navarini L, Speziali M, Vomero M, Barbati C, Perricone C, Ceccarelli F, Finucci A, Celia AI, Currado D, Afeltra A, Schininà ME, Barnaba V, Conti F, Valesini G, Al Tags: J Autoimmun Source Type: research

Alteration of CD226/TIGIT immune checkpoint on T cells in the pathogenesis of primary Sj ögren's syndrome.
CONCLUSION: CD226/TIGIT checkpoint molecules were over-expressed on T cells in pSS. Proportional and functional alteration of CD226/TIGIT expressing CD4+ T cells may be involved in the pathogenesis of pSS, and be a potential novel therapeutic target for the disease. PMID: 32466852 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - May 25, 2020 Category: Allergy & Immunology Authors: Deng C, Chen Y, Li W, Peng L, Luo X, Peng Y, Zhao L, Wu Q, Zhang W, Zhang X, Fei Y Tags: J Autoimmun Source Type: research

Autoantibodies to neutrophil extracellular traps represent a potential serological biomarker in rheumatoid arthritis.
Abstract Neutrophil extracellular traps (NETs) are networks of extracellular chromatin decorated with antimicrobial proteins, formed by neutrophils to entrap pathogens. NETs have been implicated in the generation of autoimmune reactions. Here, we investigate the reactivity of rheumatoid arthritis (RA) serum antibodies with NETs and explore whether anti-NET antibodies (ANETA) have a potential as biomarker in RA. To quantify ANETA, we developed an ELISA with NETs isolated from stimulated human neutrophils and verified the results by immunofluorescence staining of NETs. ANETA were detected in 22%-69% of RA sera. No s...
Source: Journal of Autoimmunity - May 22, 2020 Category: Allergy & Immunology Authors: de Bont CM, Stokman MEM, Faas P, Thurlings RM, Boelens WC, Wright HL, Pruijn GJM Tags: J Autoimmun Source Type: research

Long-term renal prognosis among patients with primary Sj ögren's syndrome and renal involvement: A nationwide matched cohort study.
CONCLUSIONS: Renal prognosis among patients with pSS and renal involvement is good. Although the risk of ESRD did not increase in patients with pSS, a significantly increased risk of CKD was observed in these patients, indicating the need for increased vigilance in regular monitoring for renal complications in patients with pSS. PMID: 32446704 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - May 21, 2020 Category: Allergy & Immunology Authors: Lin CY, Wu CH, Chen HA, Hsu CY, Wang LH, Su YJ Tags: J Autoimmun Source Type: research

Corrigendum to "The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China" [J. Autoimmun. 109C (2020) 102434].
Corrigendum to "The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China" [J. Autoimmun. 109C (2020) 102434]. J Autoimmun. 2020 May 15;:102487 Authors: Yang Y, Peng F, Wang R, Yang M, Guan K, Jiang T, Xu G, Sun J, Chang C PMID: 32423578 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - May 15, 2020 Category: Allergy & Immunology Authors: Yang Y, Peng F, Wang R, Yang M, Guan K, Jiang T, Xu G, Sun J, Chang C Tags: J Autoimmun Source Type: research

Risk of ankylosing spondylitis following human papillomavirus infection: A nationwide, population-based, cohort study.
Abstract OBJECTIVE: To assess the incidence rate and risk of ankylosing spondylitis (AS) in patients with previous human papillomavirus (HPV) infection compared with those without HPV infection. METHODS: All patients with HPV infection (n = 66,314) in the NHIRD (2003-2013) were individually matched with up to four control subjects without HPV infection by age and sex (n = 265,256). All of the patients were tracked until an AS event was noted. Chi-square test was used to analyze the distribution of sociodemographic characteristics in the HPV cohort and non-HPV cohort. Cox proportional hazar...
Source: Journal of Autoimmunity - May 13, 2020 Category: Allergy & Immunology Authors: Wei CY, Lin JY, Wang YT, Huang JY, Wei JC, Chiou JY Tags: J Autoimmun Source Type: research

Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood.
osa F Abstract The ready availability of human blood makes it the first choice for immuno-monitoring. However, this has been largely confined to static metrics, particularly resting T cell phenotypes. Conversely, dynamic assessments have mostly relied on cell stimulation in vitro which is subject to multiple variables. Here, immunodynamic insights from the peripheral blood are shown to be obtainable by applying a revised approach to cell-cycle analysis. Specifically, refined flow cytometric protocols were employed, assuring the reliable quantification of T cells in the S-G2/M phases of the cell-cycle (collectively...
Source: Journal of Autoimmunity - May 12, 2020 Category: Allergy & Immunology Authors: Muñoz-Ruiz M, Pujol-Autonell I, Rhys H, Long HM, Greco M, Peakman M, Tree T, Hayday AC, Di Rosa F Tags: J Autoimmun Source Type: research

Proteins in assemblages formed by phase separation possess properties that promote their transformation to autoantigens: Implications for autoimmunity.
Abstract Autoantibodies in systemic autoimmunity are directed against only ~5% of the proteome. The purpose of this study was to assess whether the properties of assemblages (also known as Membraneless Organelles and Biological Condensates) and their protein constituents partly explain the immunological selectivity of autoimmunity. Assemblages arise from phase separation of their protein components, akin to partitioning of oil droplets in water. We obtained from a prediction algorithm (Vernon et al., elife7, 2018) the propensity scores (PScores), i.e., likelihood, for phase separation of autoantigens and non-autoa...
Source: Journal of Autoimmunity - May 11, 2020 Category: Allergy & Immunology Authors: Carl PL, Fried HM, Cohen PL Tags: J Autoimmun Source Type: research

Utility of circulating serum miRNA profiles to evaluate the potential risk and severity of immune-mediated inflammatory disorders.
ía A, Sánchez-Madrid F, González-Álvaro I, Marazuela M Abstract Immune-mediated inflammatory disorders (IMID) are a group of diseases that present inflammation as a major pathogenic mechanism. They affect 15% of the population and pose a heavy socio-economic burden. Despite the growing knowledge on the etiopathogenesis of these diseases and the marked improvement in their management, there is a lack of predictive markers of IMID development or severity suitable for early diagnosis and adjustment of treatment intensity. The possibility that certain circulating miRNA profiles could be use...
Source: Journal of Autoimmunity - May 5, 2020 Category: Allergy & Immunology Authors: Martínez-Hernández R, Fuente H, Lamana A, Sampedro-Núñez M, Ramos-Levi A, Serrano-Somavilla A, García-Vicuña R, Ortiz AM, Daudén E, Llamas-Velasco M, Chicharro P, Rodríguez-Jiménez P, Sanz-García A, Sánchez-Madrid F, González-Álvaro I, Marazu Tags: J Autoimmun Source Type: research

Pirfenidone alleviates lipopolysaccharide-induced lung injury by accentuating BAP31 regulation of ER stress and mitochondrial injury.
This study aims to investigate the protective effects of pirfenidone in ALI and to explore its underlying mechanism. Pirfenidone clearly reduces LPS-triggered ALI as indicated by significant pathological alterations, reduced oxidative stress and inflammatory responses in vivo. Furthermore, pirfenidone also blocks apoptosis of LPS-induced alveolar epithelial type II (ATII) cells through inhibition of endoplasmic reticulum (ER) stress and mitochondrial injury in vivo and in vitro. A lower expression level of BAP31, an ER transmembrane protein, was found to be associated with ALI followed LPS challenge. The reintroduction of ...
Source: Journal of Autoimmunity - May 4, 2020 Category: Allergy & Immunology Authors: Du Y, Zhu P, Wang X, Mu M, Li H, Gao Y, Qin X, Wang Y, Zhang Z, Qu G, Xu G, Chang C, Li T, Fang X, Yu S Tags: J Autoimmun Source Type: research

Antibodies in cerebral cavernous malformations react with cytoskeleton autoantigens in the lesional milieu.
This study aims to identify those putative antigen(s) using monoclonal antibodies (mAbs) derived from plasma cells found in surgically removed human CCM lesions. We produced human mAbs from laser capture micro-dissected plasma cells from four CCM patients, and also germline-reverted versions. CCM mAbs were assayed using immunofluorescence on central nervous system (CNS) tissues and immunocytochemistry on human primary cell lines. Antigen characterization was performed using a combination of confocal microscopy, immunoprecipitation and mass spectrometry. Affinity was determined by enzyme-linked immunosorbent assay, and spec...
Source: Journal of Autoimmunity - April 30, 2020 Category: Allergy & Immunology Authors: Zhang D, Kinloch AJ, Srinath A, Shenkar R, Girard R, Lightle R, Moore T, Koskimäki J, Mohsin A, Carrión-Penagos J, Romanos S, Shen L, Clark MR, Shi C, Awad IA Tags: J Autoimmun Source Type: research

Corrigendum to "Clinical Significance and Immunobiology of IL-21 in Autoimmunity"[J. Autoimmun. 99C (2019) p1-14].
Corrigendum to "Clinical Significance and Immunobiology of IL-21 in Autoimmunity"[J. Autoimmun. 99C (2019) p1-14]. J Autoimmun. 2020 Apr 28;:102455 Authors: Long D, Chen Y, Wu H, Zhao M, Lu Q PMID: 32360068 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - April 28, 2020 Category: Allergy & Immunology Authors: Long D, Chen Y, Wu H, Zhao M, Lu Q Tags: J Autoimmun Source Type: research

Selective targeting of PI3K δ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases.
Selective targeting of PI3Kδ suppresses human IL-17-producing T cells and innate-like lymphocytes and may be therapeutic for IL-17-mediated diseases. J Autoimmun. 2020 Apr 28;:102435 Authors: Chen S, Paveley R, Kraal L, Sritharan L, Stevens E, Dedi N, Shock A, Shaw S, Juarez M, Yeremenko N, Baeten D, Payne A Abstract The delta isoform of phosphoinositide 3-kinase (PI3Kδ) regulates various lymphocyte functions. Considering the key pro-inflammatory role of IL-17A and IL-17F cytokines in psoriasis and spondyloarthritis (SpA), we investigated the potential of PI3Kδ blockade to suppress I...
Source: Journal of Autoimmunity - April 28, 2020 Category: Allergy & Immunology Authors: Chen S, Paveley R, Kraal L, Sritharan L, Stevens E, Dedi N, Shock A, Shaw S, Juarez M, Yeremenko N, Baeten D, Payne A Tags: J Autoimmun Source Type: research

Microscopic polyangiitis: Clinical characteristics and long-term outcomes of 378 patients from the French Vasculitis Study Group Registry.
CONCLUSION: Non-renal manifestations and several risk factors for death or relapse were frequent in this nationwide cohort. While mortality was low, and mainly due to treatment-related complications, relapses remained frequent, suggesting that MPA management can be further improved. PMID: 32340774 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - April 24, 2020 Category: Allergy & Immunology Authors: Nguyen Y, Pagnoux C, Karras A, Quéméneur T, Maurier F, Hamidou M, Le Quellec A, Chiche NJ, Cohen P, Régent A, Lifermann F, Mékinian A, Khouatra C, Hachulla E, Pourrat J, Ruivard M, Godmer P, Viallard JF, Terrier B, Mouthon L, Guillevin L, Puéchal X, Tags: J Autoimmun Source Type: research

Identification of Ribosomal Protein S4, Y-Linked 1 as a cyclosporin A plus corticosteroid resistance gene.
Abstract Combination of corticosteroids (CS) with cyclosporin A (CsA) is widely used in the treatment of autoimmune diseases, autoinflammatory diseases and transplantation rejection. However, some patients fail to respond or develop resistance to the combination regimen. In Vogt-Koyanagi-Harada (VKH) disease model, we performed RNA sequencing (RNA-seq) based transcriptomics, isobaric tags for relative and absolute quantification (iTRAQ) based proteomics and assays in vitro to screen and validate potential resistant molecules. We found that a total of 1697 differentially expressed genes (DEGs) and 21 differentially...
Source: Journal of Autoimmunity - April 21, 2020 Category: Allergy & Immunology Authors: Chang R, Chen L, Su G, Du L, Qin Y, Xu J, Tan H, Zhou C, Cao Q, Yuan G, Kijlstra A, Yang P Tags: J Autoimmun Source Type: research

The anti-viral facet of anti-rheumatic drugs: Lessons from COVID-19.
Abstract The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has posed the world at a pandemic risk. Coronavirus-19 disease (COVID-19) is an infectious disease caused by SARS-CoV-2, which causes pneumonia, requires intensive care unit hospitalization in about 10% of cases and can lead to a fatal outcome. Several efforts are currently made to find a treatment for COVID-19 patients. So far, several anti-viral and immunosuppressive or immunomodulating drugs have demonstrated some efficacy on COVID-19 both in vitro and in animal models as well as in cases series. In COVID-19 pati...
Source: Journal of Autoimmunity - April 17, 2020 Category: Allergy & Immunology Authors: Perricone C, Triggianese P, Bartoloni E, Cafaro G, Bonifacio AF, Bursi R, Perricone R, Gerli R Tags: J Autoimmun Source Type: research

The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis.
Abstract Corticosteroid associated osteonecrosis is bone death resulting from the use of chronic glucocorticoids and most commonly affects the femoral head, although the bones such as around knee joint, wrist joint and ankle joint can be affected. The pathogenesis is likely multifactorial, with genetic and environmental factors playing a role. Epigenetics may be the mechanism by which environment exerts it effects. In spite of recent discoveries, the exact pathogenesis of corticosteroid associated osteonecrosis is unknown. Over the past few years, more miRNA's have been found to be associated with osteonecrosis. T...
Source: Journal of Autoimmunity - April 16, 2020 Category: Allergy & Immunology Authors: Chang C, Greenspan A, Gershwin ME Tags: J Autoimmun Source Type: research

The progress and prospect of regulatory T cells in autoimmune diseases.
Abstract Regulatory T cells (Treg) are an important immune cell population, playing a crucial role in regulating immune tolerance and preventing autoimmune diseases. These cells consist of various cell sub-populations and generally have an immunoregulatory or suppressive role against immune responses. They also have a different cell heterogeneity and each populations has own biological characteristics. Treg deficiency, reduction, instability, reduced vitality and dysfunction all account for multiple autoimmune diseases. In this review, we have systemically reviewed Treg classification, phenotypic features, regulat...
Source: Journal of Autoimmunity - April 15, 2020 Category: Allergy & Immunology Authors: Zhang X, Olsen N, Zheng SG Tags: J Autoimmun Source Type: research

Evolving spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors results from the WHO's pharmacovigilance database.
Abstract PURPOSE: Drug-induced uveitis is a rare but sight-threatening condition. We seek to determine the spectrum of drug-induced uveitis at the era of immune checkpoint inhibitors (ICI). METHODS: Retrospective pharmacovigilance study based on adverse drug reactions reported within VigiBase, the WHO international pharmacovigilance database. We included deduplicated individual case safety reports (ICSRs) reported as 'uveitis' at Preferred Term level according to the Medical Dictionary for Drug Regulatory Activities between 1967 and 04/28/2019. We performed a case/non-case analysis to study if suspected drug-...
Source: Journal of Autoimmunity - April 14, 2020 Category: Allergy & Immunology Authors: Anquetil C, Salem JE, Lebrun-Vignes B, Touhami S, Desbois AC, Maalouf G, Domont F, Allenbach Y, Cacoub P, Bodaghi B, Saadoun D Tags: J Autoimmun Source Type: research

Assessing ACE2 expression patterns in lung tissues in the pathogenesis of COVID-19.
In this study, we utilized previously uploaded information on ACE2 expression in various conditions including SARS-CoA to evaluate the role of ACE2 in SARS-CoV and extrapolate that to COVID-19. We found that the expression of ACE2 in healthy populations and patients with underlying diseases was not significantly different. However, based on the elevated expression of ACE2 in cigarette smokers, we speculate that long-term smoking may be a risk factor for COVID-19. Analysis of ACE2 in SARS-CoV infected cells suggests that ACE2 is not only a receptor but is also involved in post-infection regulation, including immune response...
Source: Journal of Autoimmunity - April 13, 2020 Category: Allergy & Immunology Authors: Li G, He X, Zhang L, Ran Q, Wang J, Xiong A, Wu D, Chen F, Sun J, Chang C Tags: J Autoimmun Source Type: research

The pivotal role of CD69 in autoimmunity.
Abstract Autoimmune disorders are outcomes of impaired activity of the immune system regarding the maintenance of tolerance, which results in tissue damage secondary to an excess in the inflammatory response. Under normal conditions, the cells in the adaptive immune system are highly controlled to remain unresponsive against self-antigens (self-Ags) through various mechanisms and during different stages of maturation. CD69 (cluster of differentiation 69), a C-type lectin disulfide-linked homodimer, is expressed on different leukocytes, including newly-activated lymphocytes, certain subtypes of memory T-cells, infi...
Source: Journal of Autoimmunity - April 11, 2020 Category: Allergy & Immunology Authors: Gorabi AM, Hajighasemi S, Kiaie N, Gheibi Hayat SM, Jamialahmadi T, Johnston TP, Sahebkar A Tags: J Autoimmun Source Type: research

Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?
Abstract The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CR...
Source: Journal of Autoimmunity - April 10, 2020 Category: Allergy & Immunology Authors: Liu B, Li M, Zhou Z, Guan X, Xiang Y Tags: J Autoimmun Source Type: research

CXCL4 triggers monocytes and macrophages to produce PDGF-BB, culminating in fibroblast activation: Implications for systemic sclerosis.
CONCLUSION: Our findings demonstrate that CXCL4 can drive fibroblast activation indirectly via PDGF-BB production by myeloid cells. Hence, targeting PDGF-BB or CXCL4-induced PDGF-BB release could be clinically beneficial for patients with SSc. PMID: 32284212 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - April 10, 2020 Category: Allergy & Immunology Authors: van der Kroef M, Carvalheiro T, Rossato M, de Wit F, Cossu M, Chouri E, Wichers CGK, Bekker CPJ, Beretta L, Vazirpanah N, Trombetta E, Radstake TRDJ, Angiolilli C Tags: J Autoimmun Source Type: research

Precision medicine and management of rheumatoid arthritis.
Abstract Precision medicine (PM) is a very commonly used term that implies a highly individualized and tailored approach to patient management. There are, however, many layers of precision, as for example taking an appropriate patient history, or performing additional lab or imaging tests are already helping to better tailor treatments to the right patient. All this adds to the narrower definition of PM, which implies using the unique molecular characteristics of a patient for management decisions. Big data has become an essential part of PM, including as much information as possible to improve precision of diseas...
Source: Journal of Autoimmunity - April 7, 2020 Category: Allergy & Immunology Authors: Aletaha D Tags: J Autoimmun Source Type: research

Immunization with Pentraxin3 prevents transition from subclinical to clinical lupus nephritis in lupus-prone mice: Insights from renal ultrastructural findings.
CONCLUSIONS: Immunization with PTX3 prevented progression from the preclinical to the clinical stage of LN, inciting anti-PTX3 antibodies and preventing renal PTX3 deposition. PTX3 is a novel component of EDD, submitting it as one initiating autoantigen in LN and as potential target for early treatment. PMID: 32265078 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - April 4, 2020 Category: Allergy & Immunology Authors: Gatto M, Radu CM, Luisetto R, Ghirardello A, Bonsembiante F, Trez D, Valentino S, Bottazzi B, Simioni P, Cavicchioli L, Doria A Tags: J Autoimmun Source Type: research

Recommendations for coronavirus infection in rheumatic diseases treated with biologic therapy.
Abstract The Coronavirus-associated disease, that was first identified in 2019 in China (CoViD-19), is a pandemic caused by a bat-derived beta-coronavirus, named SARS-CoV2. It shares homology with SARS and MERS-CoV, responsible for past outbreaks in China and in Middle East. SARS-CoV2 spread from China where the first infections were described in December 2019 and is responsible for the respiratory symptoms that can lead to acute respiratory distress syndrome. A cytokine storm has been shown in patients who develop fatal complications, as observed in past coronavirus infections. The management includes ventilatory...
Source: Journal of Autoimmunity - April 2, 2020 Category: Allergy & Immunology Authors: Ceribelli A, Motta F, De Santis M, Ansari AA, Ridgway WM, Gershwin ME, Selmi C Tags: J Autoimmun Source Type: research

Antibodies can specifically target placental mitochondria and induce ROS production.
Abstract Women with antiphospholipid antibodies (aPL) have increased risks of pregnancy complications, including a ten-fold increased risk of preeclampsia, which is potentially triggered by the release of placental toxins. Previously, aPL were shown to enter the outer layer of the placenta, the syncytiotrophoblast, associate with mitochondria, and alter mitochondrial function. We hypothesised that aPL may also increase mitochondrial reactive oxygen species (ROS) production, leading to cellular dysfunction and release of toxins. First trimester placental explants were incubated with monoclonal aPL, ID2 and IIC5 (25...
Source: Journal of Autoimmunity - March 26, 2020 Category: Allergy & Immunology Authors: Zussman R, Xu LY, Damani T, Groom KM, Chen Q, Seers B, Viall CA, Chamley LW, Hickey A Tags: J Autoimmun Source Type: research

Multi-omics: Differential expression of IFN- γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases.
Multi-omics: Differential expression of IFN-γ results in distinctive mechanistic features linking chronic inflammation, gut dysbiosis, and autoimmune diseases. J Autoimmun. 2020 Mar 24;:102436 Authors: Bae HR, Leung PSC, Hodge DL, Fenimore JM, Jeon SM, Thovarai V, Dzutsev A, Welcher AA, Boedigheimer M, Damore MA, Choi MS, Fravell RA, Trinchieri G, Gershwin ME, Young HA Abstract Low grade, chronic inflammation is a critical risk factor for immunologic dysfunction including autoimmune diseases. However, the multiplicity of complex mechanisms and lack of relevant murine models limit our understandi...
Source: Journal of Autoimmunity - March 24, 2020 Category: Allergy & Immunology Authors: Bae HR, Leung PSC, Hodge DL, Fenimore JM, Jeon SM, Thovarai V, Dzutsev A, Welcher AA, Boedigheimer M, Damore MA, Choi MS, Fravell RA, Trinchieri G, Gershwin ME, Young HA Tags: J Autoimmun Source Type: research

TIGIT+ A2Ar-Dependent anti-uveitic Treg cells are a novel subset of Tregs associated with resolution of autoimmune uveitis.
Abstract Regulatory T cells (Tregs) are necessary to prevent autoimmune disease. As such, stable FoxP3 expression is required for the proper function of Tregs in the control of autoimmune disease. Different Treg subsets that utilize different mechanisms of suppression have been identified. The T-cell immunoglobulin immunoreceptor tyrosine-based inhibitory motif (TIGIT) is a relatively new Treg cell marker that has a suppressive function. We have previously identified the adenosine 2A receptor (A2Ar) as a requirement for the emergence of Tregs following resolution of autoimmune disease. Using a FoxP3-GFP-Cre report...
Source: Journal of Autoimmunity - March 20, 2020 Category: Allergy & Immunology Authors: Muhammad F, Wang D, McDonald T, Walsh M, Drenen K, Montieth A, Foster CS, Lee DJ Tags: J Autoimmun Source Type: research

Antagonizing miR-7 suppresses B cell hyperresponsiveness and inhibits lupus development.
CONCLUSION: The above data have demonstrated the critical roles of miR-7 not only in regulating PTEN expression and also B cell and Tfh cell function in lupus-prone MRLlpr/lpr lupus mice. Furthermore, the disease manifestations in MRLlpr/lpr lupus mice are efficiently improved by miR-7 antagomir, indicating miR-7 as a potential treatment strategy in SLE. PMID: 32201226 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - March 19, 2020 Category: Allergy & Immunology Authors: Wang M, Chen H, Qiu J, Yang HX, Zhang CY, Fei YY, Zhao LD, Zhou JX, Wang L, Wu QJ, Zhou YZ, Zhang W, Zhang FC, Lipsky PE, Zhang X Tags: J Autoimmun Source Type: research

Gene expression profiling of epithelium-associated FcRL4+ B cells in primary Sj ögren's syndrome reveals a pathogenic signature.
This study aimed to investigate the phenotype and function of FcRL4+ B cells in the periphery and parotid gland tissue of patients with pSS. First, circulating FcRL4+ B cells from 44 pSS and 54 non-SS-sicca patients were analyzed by flow cytometry. Additionally, RNA sequencing of FcRL4+ B cells sorted from parotid gland cell suspensions of 6 pSS patients was performed. B cells were sorted from cell suspensions as mini bulk (5 cells/well) based on the following definitions: CD19+CD27-FcRL4- ('naive'), CD19+CD27+FcRL4- ('memory'), and CD19+FcRL4+ B cells. We found that, although FcRL4+ B cells were not enriched in blood...
Source: Journal of Autoimmunity - March 19, 2020 Category: Allergy & Immunology Authors: Verstappen GM, Ice JA, Bootsma H, Pringle S, Haacke EA, de Lange K, van der Vries GB, Hickey P, Vissink A, Spijkervet FKL, Lessard CJ, Kroese FGM Tags: J Autoimmun Source Type: research

Clinical significance of miRNAs in autoimmunity.
Abstract MicroRNAs (miRNAs) are evolutionally conserved, single-stranded RNAs that regulate gene expression at the posttranscriptional level by disrupting translation. MiRNAs are key players in variety of biological processes that regulate the differentiation, development and activation of immune cells in both innate and adaptive immunity. The disruption and dysfunction of miRNAs can perturb the immune response, stimulate the release of inflammatory cytokines and initiate the production of autoantibodies, and contribute to the pathogenesis of autoimmune diseases, including systemic lupus erythmatosus (SLE), rheuma...
Source: Journal of Autoimmunity - March 14, 2020 Category: Allergy & Immunology Authors: Zhang L, Wu H, Zhao M, Chang C, Lu Q Tags: J Autoimmun Source Type: research

Insights into the treatment of rheumatoid arthritis: A paradigm in medicine.
Abstract Insights into rheumatoid arthritis (RA) have slowly evolved over the last century, but with breathtaking speed over the last 2 decades. While only aspirin and parenteral gold were available in early 20th century, the efficacy of sulfasalazine, glucocorticoids and methotrexate was established around its middle. Identification of pathogenetic pathways was slow, and until today the role of T-cells is enigmatic, while it is clear that genetics via the shared epitope and other genes as well as environmental factors including the metagenome play major roles. More clarity evolved on importance of proinflammatory...
Source: Journal of Autoimmunity - March 3, 2020 Category: Allergy & Immunology Authors: Smolen JS Tags: J Autoimmun Source Type: research