Chromosome 3 cluster rs11385942 variant links complement activation with severe COVID-19.
CONCLUSIONS: The rs11385949 G>GA variant, tagging the chromosome 3 gene cluster variation and predisposing to severe COVID-19, is associated with enhanced complement activation, both with C5a and terminal complement complex, while non-O blood group with C5a levels. These findings provide a link between genetic susceptibility to more severe COVID-19 and complement activation. PMID: 33453462 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - January 9, 2021 Category: Allergy & Immunology Authors: Valenti L, Griffini S, Lamorte G, Grovetti E, Uceda Renteria SC, Malvestiti F, Scudeller L, Bandera A, Peyvandi F, Prati D, Meroni P, Cugno M Tags: J Autoimmun Source Type: research

Treg-specific IL-2 therapy can reestablish intrahepatic immune regulation in autoimmune hepatitis.
In conclusion, complexed IL-2/anti-IL-2 restored the balance between Tregs and Teffs within the liver, thereby improving the course of emAIH. Treg-specific IL-2 augmentation offers new hope for reestablishing immune tolerance in patients with AIH. PMID: 33387980 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - December 30, 2020 Category: Allergy & Immunology Authors: Buitrago-Molina LE, Pietrek J, Noyan F, Schlue J, Manns MP, Wedemeyer H, Hardtke-Wolenski M, Jaeckel E Tags: J Autoimmun Source Type: research

Anti-neutrophil cytoplasmic antibodies predate symptom onset of ANCA-associated vasculitis. A case-control study.
Dahlqvist S Abstract OBJECTIVES: Anti-neutrophil cytoplasmic autoantibodies [ANCA) are important for diagnosis of ANCA-associated vasculitides (AAV). The timing of antibody development is not well established. To investigate the development of proteinase 3 (PR3)- and myeloperoxidase (MPO)-ANCA, blood samples collected before onset of symptoms of AAV were analysed. METHODS: To identify AAV patients with blood samples predating symptoms, the National Patient Register and Cause of Death register were scrutinized for ICD codes for AAV and linked to the registers of five biobanks. Diagnoses of AAV and time point f...
Source: Journal of Autoimmunity - December 16, 2020 Category: Allergy & Immunology Authors: Berglin E, Mohammad AJ, Dahlqvist J, Johansson L, Eriksson C, Sjöwall J, Rantapää-Dahlqvist S Tags: J Autoimmun Source Type: research

Early diagnosis and treatment for Sj ögren's syndrome: current challenges, redefined disease stages and future prospects.
Early diagnosis and treatment for Sjögren's syndrome: current challenges, redefined disease stages and future prospects. J Autoimmun. 2020 Dec 10;117:102590 Authors: Wang B, Chen S, Zheng Q, Li Y, Zhang X, Xuan J, Liu Y, Shi G Abstract There are some challenges and unmet needs in the early diagnosis and management of Sjögren's syndrome (SjS) such as prominent glandular dysfunction at diagnosis and long diagnostic delay. Those challenges are partly attributed to the lack of a good knowledge of the early stages of SjS, which is a major obstacle to delivering appropriate care to SjS patients. F...
Source: Journal of Autoimmunity - December 10, 2020 Category: Allergy & Immunology Authors: Wang B, Chen S, Zheng Q, Li Y, Zhang X, Xuan J, Liu Y, Shi G Tags: J Autoimmun Source Type: research

Subjects at-risk for future development of rheumatoid arthritis demonstrate a PAD4-and TLR-dependent enhanced histone H3 citrullination and proinflammatory cytokine production in CD14hi monocytes.
Abstract The presence of anti-citrullinated protein/peptide antibodies (ACPA) and epitope spreading across the target autoantigens is a unique feature of rheumatoid arthritis (RA). ACPA are present in the peripheral blood for several years prior to the onset of arthritis and clinical classification of RA. ACPA recognize multiple citrullinated proteins, including histone H3 (H3). Intracellular citrullination of H3 in neutrophils and T cells is known to regulate immune cell function by promoting neutrophil extracellular trap formation and citrullinated autoantigen release as well as regulating the Th2/Th17 T ce...
Source: Journal of Autoimmunity - December 9, 2020 Category: Allergy & Immunology Authors: Okamato Y, Ghosh T, Okamoto T, Schuyler RP, Seifert J, Charry LL, Visser A, Feser M, Fleischer C, Pedrick C, August J, Moss L, Bemis EA, Norris JM, Kuhn KA, Demoruelle MK, Deane KD, Ghosh D, Holers VM, Hsieh EWY Tags: J Autoimmun Source Type: research

Longitudinal analysis of T-cell receptor repertoires reveals persistence of antigen-driven CD4+ and CD8+ T-cell clusters in systemic sclerosis.
In conclusion, our results show that CD4+ and CD8+ T-cells are highly persistent in SSc patients over time, and this persistence is likely a result from antigenic selection. Moreover, persistent TCRs form high similarity clusters with other (non-)persistent sequences that potentially recognize the same epitopes. These data provide evidence for an antigen driven expansion of CD4+/CD8+ T-cells in SSc. PMID: 33307312 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - December 8, 2020 Category: Allergy & Immunology Authors: Servaas NH, Zaaraoui-Boutahar F, Wichers CGK, Ottria A, Chouri E, Affandi AJ, Silva-Cardoso S, van der Kroef M, Carvalheiro T, van Wijk F, Radstake TRDJ, Andeweg AC, Pandit A Tags: J Autoimmun Source Type: research

The B cell response to both protein and nucleic acid antigens displayed on apoptotic cells are dependent on endosomal pattern recognition receptors.
Abstract In systemic autoimmune diseases such as systemic lupus erythematosus (SLE), B cell tolerance is lost and there is a production of autoantibodies that drive pathology. The specificities of these antibodies are towards a wide range of autoantigens including proteins such as serum factors including cytokines as well as towards nucleic acids and modified glycolipids. It is known that endosomal pattern recognition receptors are involved in specific responses but if they drive specificity towards a specific group of autoantigens is not known. Here, we used syngeneic apoptotic cells alone to break B cell toleran...
Source: Journal of Autoimmunity - December 6, 2020 Category: Allergy & Immunology Authors: Garimella MG, He C, Chen G, Li QZ, Huang X, Karlsson MCI Tags: J Autoimmun Source Type: research

Galectin-9 bridges human B cells to vascular endothelium while programming regulatory pathways.
Abstract Humoral immunity is reliant on efficient recruitment of circulating naïve B cells from blood into peripheral lymph nodes (LN) and timely transition of naive B cells to high affinity antibody (Ab)-producing cells. Current understanding of factor(s) coordinating B cell adhesion, activation and differentiation within LN, however, is incomplete. Prior studies on naïve B cells reveal remarkably strong binding to putative immunoregulator, galectin (Gal)-9, that attenuates BCR activation and signaling, implicating Gal-9 as a negative regulator in B cell biology. Here, we investigated Gal-9 localization...
Source: Journal of Autoimmunity - December 4, 2020 Category: Allergy & Immunology Authors: Chakraborty A, Staudinger C, King SL, Erickson FC, Lau LS, Bernasconi A, Luscinskas FW, Perlyn C, Dimitroff CJ Tags: J Autoimmun Source Type: research

Mushrooms and immunity.
Abstract In the wide field of nutraceuticals, the effects of mushrooms on immunity, cancer and including autoimmunity have been proposed for centuries but in recent years a growing interest has led scientists to elucidate which specific compounds have bioactive properties and through which mechanisms. Glucans and specific proteins are responsible for most of the biological effects of mushrooms, particularly in terms of immunomodulatory and anti-tumor results. Proteins with bioactive effects include lectins, fungal immunomodulatory proteins (FIPs), ribosome inactivating proteins (RIPs), ribonucleases, laccases, amo...
Source: Journal of Autoimmunity - December 1, 2020 Category: Allergy & Immunology Authors: Motta F, Gershwin ME, Selmi C Tags: J Autoimmun Source Type: research

Rituximab plus belimumab in non-infectious refractory cryoglobulinemia vasculitis: A pilot study.
CONCLUSION: Belimumab along with rituximab showed promising results in refractory patients with CV. PMID: 33248866 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 25, 2020 Category: Allergy & Immunology Authors: Saadoun D, Ghembaza A, Riviere S, Mekinian A, Boutemy J, Leroux G, Domont F, Maillard H, Vautier M, Cacoub P Tags: J Autoimmun Source Type: research

Primary biliary cholangitis with normal alkaline phosphatase: A neglected clinical entity challenging current guidelines.
CONCLUSIONS: In our series, a high proportion of AMA positive patients with normal ALP levels have PBC. For the first time we show histological diagnosis of PBC in AMA-negative/PBC-specific ANA-positive subjects and the potential role of GGT as a biomarker in PBC patients with normal baseline ALP levels. Current guidelines for the diagnosis of PBC do not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation. PMID: 33229138 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 20, 2020 Category: Allergy & Immunology Authors: Terziroli Beretta-Piccoli B, Stirnimann G, Mertens J, Semela D, Zen Y, Mazzucchelli L, Voreck A, Kolbus N, Merlo E, Di Bartolomeo C, Messina P, Cerny A, Costantini S, Vergani D, Mieli-Vergani G, Swiss PBC Cohort Study Group Tags: J Autoimmun Source Type: research

A Guillain-Barr é syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides.
A Guillain-Barré syndrome-associated SIGLEC10 rare variant impairs its recognition of gangliosides. J Autoimmun. 2020 Nov 19;:102571 Authors: Alborzian Deh Sheikh A, Gomaa S, Li X, Routledge M, Saigoh K, Numoto N, Angata T, Hitomi Y, Takematsu H, Tsuiji M, Ito N, Kusunoki S, Tsubata T Abstract Guillain-Barré syndrome (GBS), including its variant Miller Fisher syndrome (MFS), is an acute peripheral neuropathy that involves autoimmune mechanisms leading to the production of autoantibodies to gangliosides; sialic acid-containing glycosphingolipids. Although association with various genetic ...
Source: Journal of Autoimmunity - November 19, 2020 Category: Allergy & Immunology Authors: Alborzian Deh Sheikh A, Gomaa S, Li X, Routledge M, Saigoh K, Numoto N, Angata T, Hitomi Y, Takematsu H, Tsuiji M, Ito N, Kusunoki S, Tsubata T Tags: J Autoimmun Source Type: research

Resistant starch intake alleviates collagen-induced arthritis in mice by modulating gut microbiota and promoting concomitant propionate production.
Abstract Gut dysbiosis precedes clinic symptoms in rheumatoid arthritis (RA) and has been implicated in the initiation and persistence of RA. The early treatment of RA is critical to better clinical outcome especially for joint destruction. Although dietary interventions have been reported to be beneficial for RA patients, it is unclear to whether diet-induced gut microbiome changes can be a preventive strategy to RA development. Here, we investigated the effect of a high fiber diet (HFD) rich with resistant starch (RS) on collagen-induced arthritis (CIA) and gut microbial composition in mice. RS-HFD significantly...
Source: Journal of Autoimmunity - November 14, 2020 Category: Allergy & Immunology Authors: Bai Y, Li Y, Marion T, Tong Y, Zaiss MM, Tang Z, Zhang Q, Liu Y, Luo Y Tags: J Autoimmun Source Type: research

The effect of Toll-like receptor stimulation on the motility of regulatory T cells.
In this study, we have modulated Treg dynamics using Toll-like receptor (TLR) agonists. Dynamic imaging with confocal and two-photon microscopy revealed that Tregs generated in vitro and stimulated with P3C (a TLR2 agonist) but not with R848 (a TLR7 agonist) or LPS (a TLR4 agonist) showed enhanced cell migration within splenic white pulp or draining lymph node when transferred into mice intravenously or into the footpad, respectively. In summary, our data demonstrate that Tregs are more motile in response to direct TLR stimulation in particular towards TLR2 signals. This may have implications for efficient clinical Treg in...
Source: Journal of Autoimmunity - November 11, 2020 Category: Allergy & Immunology Authors: Chodaczek G, Pagni PP, Christofferson G, Ratliff SS, Toporkiewicz M, Wegrzyn AS, von Herrath M Tags: J Autoimmun Source Type: research

The amino acid variants in HLA II molecules explain the major association with adult-onset Still's disease in the Han Chinese population.
This study reveals the relationship between functional variations in the class II HLA region and AOSD, implicating the MHC locus in the pathogenesis of AOSD. PMID: 33168359 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 6, 2020 Category: Allergy & Immunology Authors: Teng JL, Chen X, Chen J, Zeng T, He L, Li M, Luo CN, Liu S, Ding TT, Yimaiti K, Li X, Ding Y, Cheng XB, Zhou J, Ye JN, Ji J, Su YT, Shi H, Sun Y, Gao C, Hu QY, Chi HH, Yuan X, Zhou ZC, Wang D, Wang K, Feng D, Li C, Sun Y, Niu Y, Xu X, Chen LJ, Xu J, Wu LJ Tags: J Autoimmun Source Type: research

Identification of a primary antigenic target of epitope spreading in endemic pemphigus foliaceus.
Abstract Epitope spreading is an important mechanism for the development of autoantibodies (autoAbs) in autoimmune diseases. The study of epitope spreading in human autoimmune diseases is limited due to the major challenge of identifying the initial/primary target epitopes on autoantigens in autoimmune diseases. We have been studying the development of autoAbs in an endemic human autoimmune disease, Brazilian pemphigus foliaceus (or Fogo Selvagem (FS)). Our previous findings demonstrated that patients before (i.e. preclinical) and at the onset of FS have antibody (Ab) responses against other keratinocyte adhesion ...
Source: Journal of Autoimmunity - November 3, 2020 Category: Allergy & Immunology Authors: Peng B, Temple BR, Yang J, Geng S, Culton DA, Qian Y Tags: J Autoimmun Source Type: research

Complement activation and endothelial perturbation parallel COVID-19 severity and activity.
CONCLUSIONS: Complement activation is boosted during the progression of COVID-19 and dampened during remission, thus indicating its role in the pathophysiology of the disease. The association between complement activation and the biomarkers of endothelial damage suggests that complement may contribute to tissue injury and could be the target of specific therapy. PMID: 33139116 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 29, 2020 Category: Allergy & Immunology Authors: Cugno M, Meroni PL, Gualtierotti R, Griffini S, Grovetti E, Torri A, Lonati P, Grossi C, Borghi MO, Novembrino C, Boscolo M, Uceda Renteria SC, Valenti L, Lamorte G, Manunta M, Prati D, Pesenti A, Blasi F, Costantino G, Gori A, Bandera A, Tedesco F, Peyva Tags: J Autoimmun Source Type: research

Natural Killer Cell Transcript 4 promotes the development of Sj ӧgren's syndrome via activation of Rap1 on B cells.
In this study, we analyzed patient samples, utilized a transgenic mouse model and human B cells to reveal Natural Killer Cell Transcript 4 (NK4) as a novel regulator that promotes the development of autoimmune disorders. NK4 was significantly elevated in samples from patients with Sjӧgren's Syndrome (SS). SS patients show elevated NK4 levels. There is a strong and positive correlation between the increased levels of NK4 and the duration of SS. Interestingly, transgenic expression of NK4 in a mouse model led to the development of autoantibodies and lymphocytic infiltration in salivary glands similar to those in SS patients...
Source: Journal of Autoimmunity - October 18, 2020 Category: Allergy & Immunology Authors: Qu P, Wuest T, Min Y, Alevizos I, Young HA, Lin PC Tags: J Autoimmun Source Type: research

Fingolimod reduces salivary infiltrates and increases salivary secretion in a murine Sj ögren's model.
Fingolimod reduces salivary infiltrates and increases salivary secretion in a murine Sjögren's model. J Autoimmun. 2020 Oct 12;:102549 Authors: Cohen PL, McCulloch A Abstract Sjögren's Syndrome (SjS) is a chronic, systemic autoimmune disease causing xerostomia, xerophthalmia, and systemic symptoms. The principal pathological finding in SjS is the accumulation of lymphocytes in exocrine glandular tissue and elsewhere, leading to secretory dysfunction and other abnormalities. A rational therapeutic approach might be to interfere with lymphocyte migration to the periphery from central lymphoid ...
Source: Journal of Autoimmunity - October 12, 2020 Category: Allergy & Immunology Authors: Cohen PL, McCulloch A Tags: J Autoimmun Source Type: research

Integrated bulk and single-cell RNA-sequencing identified disease-relevant monocytes and a gene network module underlying systemic sclerosis.
CONCLUSIONS: Our integrated analysis of bulk and single cell RNA-seq analysis identified an inflammatory gene module and a cluster of monocytes that are relevant to SSc pathophysiology. They could serve as candidate novel therapeutic targets in SSc. PMID: 33039247 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 7, 2020 Category: Allergy & Immunology Authors: Kobayashi S, Nagafuchi Y, Okubo M, Sugimori Y, Shirai H, Hatano H, Junko M, Yanaoka H, Takeshima Y, Ota M, Iwasaki Y, Sumitomo S, Okamura T, Yamamoto K, Shoda H, Fujio K Tags: J Autoimmun Source Type: research

Corrigendum to "The pivotal role of CD69 in autoimmunity" [J. Autoimmun. 111C (2020) 102453].
Corrigendum to "The pivotal role of CD69 in autoimmunity" [J. Autoimmun. 111C (2020) 102453]. J Autoimmun. 2020 Sep 30;:102548 Authors: Gorabi AM, Hajighasemi S, Kiaie N, Gheibi Hayat SM, Jamialahmadi T, Johnston TP, Sahebkar A PMID: 33011022 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 29, 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

Corrigendum to "Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity" [J. Autoimmun. 105C (2019) 102300].
Corrigendum to "Selective deletion of Eos (Ikzf4) in T-regulatory cells leads to loss of suppressive function and development of systemic autoimmunity" [J. Autoimmun. 105C (2019) 102300]. J Autoimmun. 2020 Sep 24;:102544 Authors: Gokhale AS, Gangaplara A, Lopez-Occasio M, Thornton AM, Shevach EM PMID: 32981806 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 23, 2020 Category: Allergy & Immunology Authors: Gokhale AS, Gangaplara A, Lopez-Occasio M, Thornton AM, Shevach EM Tags: J Autoimmun Source Type: research

Modulating the wayward T cell: New horizons with immune checkpoint inhibitor treatments in autoimmunity, transplant, and cancer.
Abstract The T-cell response is regulated by the balance between costimulatory and coinhibitory signals. Immune checkpoints are essential for efficient T-cell activation, but also for maintaining self-tolerance and protecting tissues from damage caused by the immune system, and for providing protective immunity. Modulating immune checkpoints can serve diametric goals, such that blocking a coinhibitory molecule can unleash anti-cancer immunity whereas stimulating the same molecule can reduce an over-reaction in autoimmune disease. The purpose of this review is to examine the regulation of T-cell costimulation and c...
Source: Journal of Autoimmunity - September 22, 2020 Category: Allergy & Immunology Authors: Calabrese LH, Caporali R, Blank CU, Kirk AD Tags: J Autoimmun Source Type: research

Prevalence of COVID infections in a population of rheumatic patients from Lombardy and Marche treated with biological drugs or small molecules: A multicentre retrospective study.
CONCLUSIONS: Our findings suggest that the susceptibility of rheumatic patients to COVID-19 is the same as that of the general population, but confirm that age, disease duration, and the number of co-morbidities are associated with an increased risk of a severe form of the disease. It seems that immunosuppressants drugs do not effectively represent a risk factor for COVID- 19. PMID: 32972804 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 20, 2020 Category: Allergy & Immunology Authors: Piercarlo SP, Daniela M, Roberto C, Carlo Maurizio M, Ennio Giulio F, Franco F, Michela F, Silvia B, Chiara B, Sara B, Valeria G, Alberto B, Antonella C, Patrizia B, Lorenzo D, Silvia S, Viviana R, Silvia T, Sonia F, Paola F, Laura C, Maria LA, Massimo G, Tags: J Autoimmun Source Type: research

Retro-inverso D-peptides as a novel targeted immunotherapy for Type 1 diabetes.
Abstract Over the past four decades, the number of people with Type 1 Diabetes (T1D) has increased by 4% per year, making it an important public health challenge. Currently, no curative therapy exists for T1D and the only available treatment is insulin replacement. HLA-DQ8 has been shown to present antigenic islet peptides driving the activation of CD4+ T-cells in T1D patients. Specifically, the insulin peptide InsB:9-23 activates self-reactive CD4+ T-cells, causing pancreatic beta cell destruction. The aim of the current study was to identify retro-inverso-d-amino acid based peptides (RI-D-peptides) that can supp...
Source: Journal of Autoimmunity - September 16, 2020 Category: Allergy & Immunology Authors: Lombardi A, Concepcion E, Hou H, Arib H, Mezei M, Osman R, Tomer Y Tags: J Autoimmun Source Type: research

Cardiac involvement in adult-onset Still's disease: Manifestations, treatments and outcomes in a retrospective study of 28 patients.
CONCLUSION: Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis. PMID: 32943282 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 14, 2020 Category: Allergy & Immunology Authors: Bodard Q, Langlois V, Guilpain P, Le Quellec A, Vittecoq O, Noel D, Eble V, Josse S, Schmidt J, Aouba A, Levesque H, Le Besnerais M, Benhamou Y Tags: J Autoimmun Source Type: research

Do RA associated HLA-DR molecules bind citrullinated peptides or peptides from PAD4 to help the development of RA specific antibodies to citrullinated proteins?
Abstract PURPOSE: Rheumatoid arthritis (RA) is associated with HLA-DRB1 genes encoding a five amino acid basic motive, the shared epitope SE). Each HLA-DRB1 genotype defines a genotype specific risk of developing RA. RA is preceded by the emergence of anti citrullinated protein antibodies (ACPAs). Citrullin is a neutral version of arginin, a basic amino acid, formed after post translational modification by Peptidyl Arginyl Deiminases (PADs). HLA-DRB1 genes associated with RA are also associated with ACPAs. Two models might explain this association. Here we tested both models for prediction of HLA-DRB1 genotypic ri...
Source: Journal of Autoimmunity - September 10, 2020 Category: Allergy & Immunology Authors: Balandraud N, Auger I, Roudier J Tags: J Autoimmun Source Type: research

Extracellular vesicles and lupus nephritis - New insights into pathophysiology and clinical implications.
Abstract Lupus nephritis (LN) is a major cause for overall morbidity and mortality in patients with systemic lupus erythematosus (SLE), while its pathogenic mechanisms are still not well understood. Extracellular vesicles (EVs) are membrane vesicles that are released from almost all cell types. EVs can be subdivided into exosomes, microvesicles, and apoptotic bodies. Latest studies have shown that EVs can be released during several cellular events, including cell activation, autophagy, and several types of programed cell death, i.e. apoptosis, necroptosis, pyroptosis, and NETosis. Emerging evidence demonstrates th...
Source: Journal of Autoimmunity - September 3, 2020 Category: Allergy & Immunology Authors: Zhao Y, Wei W, Liu ML Tags: J Autoimmun Source Type: research

High dose subcutaneous Anakinra to treat acute respiratory distress syndrome secondary to cytokine storm syndrome among severely ill COVID-19 patients.
onzález BV, Alemán AA, Martín LB Abstract OBJECTIVE: Severely ill COVID-19 patients may end in acute respiratory distress syndrome (ARDS) and multi-organ failure. Some of them develop a systemic hyperinflammatory state produced by the massive release of inflammatory agents, known as cytokine storm syndrome (CSS). Inhibition of IL-1 by Anakinra (ANK) is a potential life-saving therapy for severe CSS cases. We propose a rationale for the use of subcutaneous ANK and review our initial experience in a small cohort of severe COVID-19 CSS patients. METHODS: Retrospective cohort study of COVID-1...
Source: Journal of Autoimmunity - August 19, 2020 Category: Allergy & Immunology Authors: Julián EI, Veloso ML, de la Torre Ferrera N, Vengoechea JCB, Delgado-López PD, Burlato MC, Iglesias MU, Baladía MM, Martín AL, de la Iglesia JM, Muñoz JPG, Sebastián RS, González BV, Alemán AA, Martín LB Tags: J Autoimmun Source Type: research

Prospects for the potential of RNA interference in the treatment of autoimmune diseases: Small interfering RNAs in the spotlight.
Abstract The identification of RNA interference (RNAi) has caused a growing interest in harnessing its potential in the treatment of different diseases. Modulation of dysregulated genes through targeting by RNAi represents a potential approach with which to alter the biological pathways at a post-transcriptional level, especially as it pertains to autoimmunity and malignancy. Short hairpin RNAs (shRNA), short interfering RNAs (siRNA), and microRNAs (miRNA) are mainly involved as effector mechanisms in the targeting of RNAi biological pathways. The manipulation and delivery of these molecules in an efficient way pr...
Source: Journal of Autoimmunity - August 7, 2020 Category: Allergy & Immunology Authors: Gorabi AM, Kiaie N, Aslani S, Jamialahmadi T, Johnston TP, Sahebkar A Tags: J Autoimmun Source Type: research

Best practices for detection, assessment and management of suspected immune-mediated liver injury caused by immune checkpoint inhibitors during drug development.
lasani NP Abstract Immune checkpoint inhibitors (ICIs) have shown significant efficacy in patients with various malignancies, however, they are associated with a wide range of immune-related toxicities affecting many organs, including the liver. Immune-mediated liver injury caused by checkpoint inhibitors (ILICI) is a distinctive form of drug induced liver injury (DILI), that differs from most DILI types in presumed underlying mechanism, incidence, and response to therapeutic interventions. Despite increased awareness of ILICI and other immune-related adverse effects of ICIs reflected by recent guidelines for thei...
Source: Journal of Autoimmunity - August 3, 2020 Category: Allergy & Immunology Authors: Regev A, Avigan MI, Kiazand A, Vierling JM, Lewis JH, Omokaro SO, Di Bisceglie AM, Fontana RJ, Bonkovsky HL, Freston JW, Uetrecht JP, Miller ED, Pehlivanov ND, Haque SA, Harrison MJ, Kullak-Ublick GA, Li H, Patel NN, Patwardhan M, Price KD, Watkins PB, Ch Tags: J Autoimmun Source Type: research

12/15-Lipoxygenase choreographs the resolution of IgG-mediated skin inflammation.
ik CD Abstract Autoimmune diseases are defined by an immune response against a specific autoantigen, driven by antigen-specific T cells or antibodies. While the mechanisms resolving brief episodes of acute inflammation elicited by microbial components or tissue injury are well understood, the mechanisms resolving tissue inflammation in autoimmune diseases are still largely elusive. We have, therefore, addressed the mechanisms of resolution in IgG-mediated autoimmune diseases using a mouse model of the pemphigoid disease "bullous pemphigoid-like epidermolysis bullosa acquisita" (BP-like EBA) as prototypic...
Source: Journal of Autoimmunity - August 3, 2020 Category: Allergy & Immunology Authors: Sezin T, Ferreirós N, Jennrich M, Ochirbold K, Seutter M, Attah C, Mousavi S, Zillikens D, Geisslinger G, Sadik CD Tags: J Autoimmun Source Type: research

Bi-directional communication: Conversations between fibroblasts and immune cells in systemic sclerosis.
Abstract Systemic Sclerosis (SSc) is an autoimmune idiopathic connective tissue disease, characterized by aberrant fibro-proliferative and inflammatory responses, causing fibrosis of multiple organs. In recent years the interactions between innate and adaptive immune cells with resident fibroblasts have been uncovered. Cross-talk between immune and stromal cells mediates activation of stromal cells to myofibroblasts; key cells in the pathophysiology of fibrosis. These cells and their cytokines appear to mediate their effects in both a paracrine and autocrine fashion. This review examines the role of innate and ada...
Source: Journal of Autoimmunity - July 23, 2020 Category: Allergy & Immunology Authors: Worrell JC, O'Reilly S Tags: J Autoimmun Source Type: research

The role of thrombospondin-1 in the pathogenesis of antiphospholipid syndrome.
CONCLUSIONS: TSP-1 is probably implicated in the pathogenesis of APS. In vitro cell treatments along with high TSP-1 levels in plasma of APS patients suggest that high TSP-1 levels could mark a prothrombotic state and an underlying inflammatory process. PMID: 32709480 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 20, 2020 Category: Allergy & Immunology Authors: Patsouras M, Tsiki E, Karagianni P, Vlachoyiannopoulos PG Tags: J Autoimmun Source Type: research

Type I IFN signaling in T regulatory cells modulates chemokine production and myeloid derived suppressor cells trafficking during EAE.
This study demonstrates that signaling by type I IFNs in Tregs reduces their capacity to suppress chemokine production, with resultant alteration of the entire microenvironment of draining lymph nodes leading to enhancement of MDSC homing, and beneficial effects on disease outcome. PMID: 32709481 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 20, 2020 Category: Allergy & Immunology Authors: Tanwar S, Oguz C, Metidji A, Dahlstrom E, Barbian K, Kanakabandi K, Sykora L, Shevach EM Tags: J Autoimmun Source Type: research

Recent advances in the NEK7-licensed NLRP3 inflammasome activation: Mechanisms, role in diseases and related inhibitors.
Abstract The nucleotide-binding oligomerization domain (NOD)-like receptor containing pyrin domain 3 (NLRP3) inflammasome is a high-molecular-weight complex mediated by the activation of pattern-recognition receptors (PRRs) seed in innate immunity. Once NLRP3 is activated, the following recruitment of the adapter apoptosis-associated speck-like protein containing a caspase recruitment domain (CARD) (ASC) and procaspase-1 would be initiated. Cleavage of procaspase-1 into active caspase-1 then leads to the maturation of the precursor forms of interleukin (IL)-1β and IL-18 into biologically active IL-1β and...
Source: Journal of Autoimmunity - July 19, 2020 Category: Allergy & Immunology Authors: Zhao N, Li CC, Di B, Xu LL Tags: J Autoimmun Source Type: research

Antiphospholipid autoantibody detection is important in all patients with systemic autoimmune diseases.
Abstract Antiphospholipid (aPL) autoantibodies are uncommon in systemic autoimmune diseases (SADs). However, the European PRECISESADS study provides the opportunity to better characterize this rare association. The study was composed of 1818 patients with SADs including 453 with systemic lupus erythematosus (SLE), 359 with rheumatoid arthritis (RA), 385 with systemic sclerosis (SSc), 367 with Sjögren's syndrome (SjS), 94 with mixed connective tissue disease (MCTD), and 160 with undifferentiated connective tissue disease (UCTD). Assays used for aPL determination include the lupus anticoagulant (LAC) analysis u...
Source: Journal of Autoimmunity - July 17, 2020 Category: Allergy & Immunology Authors: Marziale A, Bettacchioli E, Picart G, Nafai S, Galinat H, Meroni PL, Frostegard J, PRECISESADS Clinical Consortium, Alarcon-Riquelme ME, Renaudineau Y Tags: J Autoimmun Source Type: research

Experience with tocilizumab in severe COVID-19 pneumonia after 80 days of follow-up: A retrospective cohort study.
CONCLUSIONS: In a Mediterranean cohort, use of tocilizumab for severe COVID-19 show 12.9% of mortality. Early TCZ-response by BCRSS and low comorbidity were associated with increased survival. Early TCZ-response was related to shorter median hospital stay. PMID: 32690352 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - July 15, 2020 Category: Allergy & Immunology Authors: Moreno-Pérez O, Andres M, Leon-Ramirez JM, Sánchez-Payá J, Rodríguez JC, Sánchez R, García-Sevila R, Boix V, Gil J, Merino E Tags: J Autoimmun Source Type: research

Clinical characteristics and predictors of survival in adults with coronavirus disease 2019 receiving tocilizumab.
Abstract Coronavirus disease 2019 (COVID-19) can progress to cytokine storm that is associated with organ dysfunction and death. The purpose of the present study is to determine clinical characteristics associated with 28 day in-hospital survival in patients with coronavirus disease 2019 (COVID-19) that received tocilizumab. This was a retrospective observational cohort study conducted at a five hospital health system in Michigan, United States. Adult patients with confirmed COVID-19 that were admitted to the hospital and received tocilizumab for cytokine storm from March 1, 2020 through April 3, 2020 were include...
Source: Journal of Autoimmunity - July 2, 2020 Category: Allergy & Immunology Authors: Morrison AR, Johnson JM, Griebe KM, Jones MC, Stine JJ, Hencken LN, To L, Bianchini ML, Vahia AT, Swiderek J, Ramesh MS, Peters MA, Smith ZR Tags: J Autoimmun Source Type: research

Prostaglandin D2 signaling in dendritic cells is critical for the development of EAE.
man S Abstract Priming of autoreactive T cells in lymph nodes by dendritic cells (DCs) is critical for the pathogenesis of experimental autoimmune encephalitis (EAE). DC activation reflects a balance of pro- and anti-inflammatory signals. One anti-inflammatory factor is prostaglandin D2 signaling through its cognate receptor, D-prostanoid receptor 1 (PTGDR), on myeloid cells. Loss of PTGDR signaling might be expected to enhance DC activation and EAE but here we show that PTGDR-/- mice developed only mild signs of MOG35-55 peptide immunization-induced EAE. Compared to wild type mice, PTGDR-/- mice exhibited less de...
Source: Journal of Autoimmunity - July 1, 2020 Category: Allergy & Immunology Authors: Zheng J, Sariol A, Meyerholz D, Zhang Q, Abrahante Lloréns JE, Narumiya S, Perlman S Tags: J Autoimmun Source Type: research

The roles of PPAR γ and its agonists in autoimmune diseases: A comprehensive review.
The roles of PPARγ and its agonists in autoimmune diseases: A comprehensive review. J Autoimmun. 2020 Jul 01;:102510 Authors: Liu Y, Wang J, Luo S, Zhan Y, Lu Q Abstract Autoimmune diseases are common diseases of the immune system that are characterized by the loss of self-tolerance and the production of autoantibodies; the breakdown of immune tolerance and the prolonged inflammatory reaction are undisputedly core steps in the initiation and maintenance of autoimmunity. Peroxisome proliferator-activated receptors (PPARs) are ligand-dependent transcription factors that belong to the nuclear hormo...
Source: Journal of Autoimmunity - June 30, 2020 Category: Allergy & Immunology Authors: Liu Y, Wang J, Luo S, Zhan Y, Lu Q Tags: J Autoimmun Source Type: research

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 26, 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 24, 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 23, 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 21, 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 21, 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 19, 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 17, 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 17, 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 15, 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