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Rheumatology (Oxford). 2016 Dec 24. pii: kew407. doi: 10.1093/rheumatology/kew407. [Epub ahead of print] 
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Type I interferon is a potent substance. As such, the induction, transmission, and resolution of the type I interferon–mediated immune response are tightly regulated. As defined, the type I interferonopathies represent discrete examples of a disturbance of the homeostatic control of this system caused by Mendelian mutations. Considering the complexity of the interferon response, the identification of further monogenic diseases belonging to this disease grouping seems likely, with the recognition of type I interferonopathies becoming of increasing clinical importance as treatment options are developed based on an understanding of disease pathology and innate immune signaling. Definition of the type I interferonopathies indicates that autoinflammation can be both interferon and noninterferon related, and that a primary disturbance of the innate immune system can “spill over” into autoimmunity in some cases. Indeed, that several non-Mendelian disorders, most particularly systemic lupus erythematosus and dermatomyositis, are also characterized by an up-regulation of type I interferon signaling suggests the possibility that insights derived from this work will have relevance to a broader field of clinical medicine.
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What is the ANA blood test and how is it connected to autoimmune disorders and lupus? Learn about what happens after a positive ANA test.
Gilbert C FAURE's insight:
too bad, ANA are not pathogenic
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RT @BiomedJ: Purinergic signalling in #autoimmunity: A role for the P2X7R in systemic lupus erythematosus? https://t.co/wQ21zD6xSg #immunol…
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Proc Natl Acad Sci U S A. 2016 Sep 1. pii: 201607101. [Epub ahead of print]
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Low-dose IL-2 treatment alters the abundance of regulatory T cells, IL-17-producing T cells and follicular helper T cells, but not of T helper type 1 and 2 cells, in patients with SLE. Via Marcelo de Carvalho Bittencourt
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International Congress on Systemic Lupus Erythematosus (LUPUS 2017) Asian Congress on Autoimmunity (ACA 2017) The 12th International Congress on SLE (LUP
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The 12th International Congress on SLE (LUPUS 2017) and the 7th Asian Congress on Autoimmunity (ACA 2017) will take place 26-29 March 2017 in Melbourne, Australia.
Gilbert C FAURE's insight:
Fabien Vincent at Monash
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Regulatory T cells (Tregs) are capable of dampening immune-mediated inflammation and avert the destructive effects of uncontrolled inflammation.
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T follicular helper (TFH) cells are a subset of T cells that provide help to B cells to produce antibodies. Dysregulation of TFH cells is associated with autoimmune diseases, such as systemic lupus erythematosus (SLE).
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J Autoimmun. 2016 Jul 5. pii: S0896-8411(16)30098-1. doi: 10.1016/j.jaut.2016.06.020. [Epub ahead of print] REVIEW
Gilbert C FAURE's insight:
Abstract One of the major disappointments in human autoimmunity has been the relative failure on genome-wide association studies to provide "smoking genetic guns" that would explain the critical role of genetic susceptibility to loss of tolerance. It is well known that autoimmunity refers to the abnormal state that the dysregulated immune system attacks the healthy cells and tissues due to the loss of immunological tolerance to self-antigens. Its clinical outcomes are generally characterized by the presence of autoreactive immune cells and (or) the development of autoantibodies, leading to various types of autoimmune disorders. The etiology and pathogenesis of autoimmune diseases are highly complex. Both genetic predisposition and environmental factors such as nutrition, infection, and chemicals are implicated in the pathogenic process of autoimmunity, however, how much and by what mechanisms each of these factors contribute to the development of autoimmunity remain unclear. Epigenetics, which refers to potentially heritable changes in gene expression and function that do not involve alterations of the DNA sequence, has provided us with a brand new key to answer these questions. In the recent decades, increasing evidence have demonstrated the roles of epigenetic dysregulation, including DNA methylation, histone modification, and noncoding RNA, in the pathogenesis of autoimmune diseases, especially systemic lupus erythematosus (SLE), which have shed light on a new era for autoimmunity research. Notably, DNA hypomethylation and reactivation of the inactive X chromosome are two epigenetic hallmarks of SLE. We will herein discuss briefly how genetic studies fail to completely elucidate the pathogenesis of autoimmune diseases and present a comprehensive review on landmark epigenetic findings in autoimmune diseases, taking SLE as an extensively studied example. The epigenetics of other autoimmune diseases such as rheumatic arthritis, systemic sclerosis and primary biliary cirrhosis will also be summarized. Importantly we emphasize that the stochastic processes that lead to DNA modification may be the lynch pins that drive the initial break in tolerance.
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Systemic lupus erythematosus (SLE) is a potentially fatal, chronic autoimmune disorder.
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Scurfy mice are deficient in regulatory T cells (Tregs), develop a severe, generalized autoimmune disorder that can affect almost every organ and die at an early age. Some of these manifestations resemble those found in systemic lupus erythematosus (SLE). In addition, active SLE is associated with low Treg numbers and reduced Treg function, but direct evidence for a central role of Treg malfunction in the pathophysiology of lupus-like manifestations is still missing. In the present study, we characterize the multiorgan pathology, autoantibody profile and blood count abnormalities in scurfy mice and show their close resemblances to lupus-like disease. Scurfy mice have dysfunctional Tregs due to a genetic defect in the transcription factor Forkhead box protein 3 (Foxp3). We analyzed skin, joints, lung and kidneys of scurfy mice and wild-type (WT) controls by conventional histology and immunofluorescence (IF) performed hematological workups and tested for autoantibodies by IF, immunoblotting and enzyme-linked immunosorbent assay. We also analyzed the intestines, liver, spleen and heart, but did not analyze all organs known to be affected in scurfy mice (such as the testicle, the accessory reproductive structures, the pancreas or the eyes). We transferred CD4+ T cells of scurfy or WT mice into T cell-deficient B6/nude mice. We confirm previous reports that scurfy mice spontaneously develop severe pneumonitis and hematological abnormalities similar to those in SLE. We show that scurfy mice (but not controls) exhibited additional features of SLE: severe interface dermatitis, arthritis, mesangioproliferative glomerulonephritis and high titers of anti-nuclear antibodies, anti-double-stranded DNA antibodies, anti-histone antibodies and anti-Smith antibodies. Transfer of scurfy CD4+ T cells (but not of WT cells) induced autoantibodies and inflammation of lung, skin and kidneys in T cell-deficient B6/nude mice. Our observations support the hypothesis that lupus-like autoimmune features develop in the absence of functional Tregs.
Gilbert C FAURE's insight:
missed it
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Clin Exp Immunol. 2016 Nov 23. doi: 10.1111/cei.12903. [Epub ahead of print] Review
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The antiphospholipid syndrome in patients with systemic lupus erythematosus https://t.co/BZkfNcPgRF #autoimmunity #feedly
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The 41-year-old mother-of-two came close to death in the summer, after she contracted a virus causing her organs to shut down.
Gilbert C FAURE's insight:
lupus awareness? Kéllé Bryan-Gudgeon is a British singer, actress and television personality, best known as a member of girl group Eternal.
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J Leukoc Biol. 2016 Sep 14. pii: jlb.3A1215-535R. [Epub ahead of print]
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Eur J Immunol. 2016 Sep 7. doi: 10.1002/eji.201646573. [Epub ahead of print]
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Gilbert C FAURE's insight:
Pathological inflammation resulting from autoimmune, inflammatory, and infectious diseases remains the major cause of morbidity and mortality around the world. We explored the utility of nucleic acid-binding polymers to limit pathological activation of the innate immune response by scavenging nucleic acid-containing debris. We evaluated such polymers following local and systemic delivery for treatment of cutaneous and systemic lupus erythematosus in mice and observed dramatic therapeutic benefit. Remarkably, such treatment does not limit the ability of lupus-prone mice to combat influenza infection. Thus, by selectively targeting activators of the pathogenic immune response rather than the effectors of the innate immune system, nucleic acid scavengers are able to limit pathological inflammation without compromising one’s ability to fight a viral infection.
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10th European Lupus: #10LupusMeeting 20 GREAT THINGS TO DO IN #VENICE - Take a… https://t.co/ujmyQi4vur #MedicBoard https://t.co/vcu4MH28SN
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LAPping up dead cells to prevent #lupus #nephritis: a novel role for noncanonical autophagy in autoimmunity https://t.co/rn6sKTbJk1 -KI
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RT @JExpMed: New in @JExpMed - Siglec-H protects from virus-triggered severe systemic autoimmunity https://t.co/vpSLeWNwfc
Gilbert C FAURE's insight:
ABSTRACT It is controversial whether virus infections can contribute to the development of autoimmune diseases. Type I interferons (IFNs) are critical antiviral cytokines during virus infections and have also been implicated in the pathogenesis of systemic lupus erythematosus. Type I IFN is mainly produced by plasmacytoid dendritic cells (pDCs). The secretion of type I IFN of pDCs is modulated by Siglec-H, a DAP12-associated receptor on pDCs. In this study, we show that Siglec-H–deficient pDCs produce more of the type I IFN, IFN-α, in vitro and that Siglec-H knockout (KO) mice produce more IFN-α after murine cytomegalovirus (mCMV) infection in vivo. This did not impact control of viral replication. Remarkably, several weeks after a single mCMV infection, Siglec-H KO mice developed a severe form of systemic lupus–like autoimmune disease with strong kidney nephritis. In contrast, uninfected aging Siglec-H KO mice developed a mild form of systemic autoimmunity. The induction of systemic autoimmune disease after virus infection in Siglec-H KO mice was accompanied by a type I IFN signature and fully dependent on type I IFN signaling. These results show that Siglec-H normally serves as a modulator of type I IFN responses after infection with a persistent virus and thereby prevents induction of autoimmune disease.
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