Background: Anticytokine autoantibodies occur across a range of hematologic, pulmonary and infectious diseases, however, systematic investigation of their presence and significance in autoimmune diseases is lacking.
AUTOIMMUNITY
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Lupus-specific anti-ribosomal P (anti-Rib-P) autoantibodies have been implicated in the pathogenesis of neurological complications in systemic lupus erythematosus (SLE). 
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Mitochondria could provoke the inflammation characteristic of lupus, an autoimmune disorder affecting the joints, skin, heart and brain.
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The complement component C1q is known to play a controversial role in the pathogenesis of systemic lupus erythematosus, but the underlying mechanisms remain poorly understood.
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Nature Immunology (2015) doi:10.1038/ni.3326Received 25 August 2015 Accepted 19 October 2015 Published online 21 December 2015
Gilbert C FAURE's insight:
Canonically, immunoglobulin E (IgE) mediates allergic immune responses by triggering mast cells and basophils to release histamine and type 2 helper cytokines. Here we found that in human systemic lupus erythematosus (SLE), IgE antibodies specific for double-stranded DNA (dsDNA) activated plasmacytoid dendritic cells (pDCs), a type of cell of the immune system linked to viral defense, which led to the secretion of substantial amounts of interferon-α (IFN-α). The concentration of dsDNA-specific IgE found in patient serum correlated with disease severity and greatly potentiated pDC function by triggering phagocytosis via the high-affinity FcεRI receptor for IgE, followed by Toll-like receptor 9 (TLR9)-mediated sensing of DNA in phagosomes. Our findings expand the known pathogenic mechanisms of IgE-mediated inflammation beyond those found in allergy and demonstrate that IgE can trigger interferon responses capable of exacerbating self-destructive autoimmune responses.
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Earlier studies showed that the DNA-binding protein, Bright/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression.
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William L. Nichols, M.D., discusses testing guidelines for lupus anticoagulant and antiphospholipid antibodies as part of the Mayo Medical Laboratories sympo...
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Ro52 is an interferon-inducible protein of the tripartite motif family.
Gilbert C FAURE's insight:
According to the literature, the CC domain is the main immunogenic region in patients with systemic lupus erythematosus (SLE), SjS, and IIM. The C-terminal region of Ro52, containing the B30.2 domain, showed higher antibody titers only in patients with SjS [21], [22]. Several laboratory methods can be used to detect antibodies to the full Ro52 molecule (immunoenzymatic assay, line immunoassay, counterimmunoelectrophoresis, Western blot, chemiluminescence, and addressable laser bead immunoassay). Epitope recognition profiles have been analyzed only in anti-Ro52–positive mothers of children with congenital heart block to identify mothers at high risk for having affected children, and it has been suggested that a high ratio between antibody titers to 200–239 aa and 176–196 aa could be used as a marker of heart block risk [16], [17]. This approach stemmed from the observed dominant response to 200–239 aa in all mothers who gave birth to affected children, while antibodies against this peptide were significantly less frequent in mothers who gave birth to healthy children. Instead, sera from the latter mothers reacted mainly with epitopes contained within 176–196 aa of the Ro52 protein. The aim of our present study was to extend the examination of Ro52 epitope antibody profiles to patients with SARDs and to assess the prevalence of antibodies to the five Ro52 fragments and to Ro52 176–196-aa and Ro52 200–239-aa peptides. Furthermore, as antibodies against the entire Ro52 molecule are not disease-specific, we also aimed to evaluate if the antibodies against any single epitope or a combination of epitopes could have more disease specificity than antibodies against the full-length protein.
nice exploration of the Ro52 antoantigen
previous papers through http://www.scoop.it/t/autoimmunity?q=Ro52
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In lupus, the immune system goes haywire and produces antibodies that are directed against the body itself.
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Plasmacytoid dendritic cells (pDCs) are professional type I IFN producers believed to promote lupus. However, questions exist about whether they function at the same level throughout the course of lupus disease.
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by Sean J. Bradley, Abel Suarez-Fueyo, David R. Moss, Vasileios C. Kyttaris, George C. Tsokos
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Clin Rev Allergy Immunol. 2015 Feb 17. [Epub ahead of print]
Gilbert C FAURE's insight:
Abstract
Autoimmune diseases are a family of chronic systemic inflammatory disorders, characterized by the dysregulation of the immune system which finally results in the break of tolerance to self-antigen. Several studies suggest that Toll-like receptors (TLRs) play an essential role in the pathogenesis of autoimmune diseases. TLRs belong to the family of pattern recognition receptors (PRRs) that recognize a wide range of pathogen-associated molecular patterns (PAMPs). TLRs are type I transmembrane proteins and located on various cellular membranes. Two main groups have been classified based on their location; the extracelluar group referred to the ones located on the plasma membrane while the intracellular group all located in endosomal compartments responsible for the recognition of nucleic acids. They are released by the host cells and trigger various intracellular pathways which results in the production of proinflammatory cytokines, chemokines, as well as the expression of co-stimulatory molecules to protect against invading microorganisms. In particular, TLR pathway-associated proteins, such as IRAK, TRAF, and SOCS, are often dysregulated in this group of diseases. TLR-associated gene expression profile analysis together with single nucleotide polymorphism (SNP) assessment could be important to explain the pathomechanism driving autoimmune diseases. In this review, we summarize recent findings on TLRpathway regulation in various autoimmune diseases, including Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), multiple sclerosis (MS), rheumatoid arthritis (RA), systemic sclerosis (SSc), and psoriasis.
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SLE links to Alu elements
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BMC Nephrol. 2015 Mar 30;16:40. doi: 10.1186/s12882-015-0032-6. Case Reports; Research Support, Non-U.S. Gov't
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Systemic lupus erythematosus (SLE) has preponderance in women in their childbearing years; consequently pregnancy has always been an important issue of concern for the patient and the treating physician.
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Ann Rheum Dis. 2016 Jan 18. pii: annrheumdis-2015-208441. doi: 10.1136/annrheumdis-2015-208441. [Epub ahead of print]
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Int J Rheum Dis. 2015 Feb;18(2):208-18. doi: 10.1111/1756-185X.12534. Epub 2015 Jan 3. Research Support, Non-U.S. Gov't; Review
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Systemic Lupus Erythematosus (SLE) is characterized by a wide spectrum of auto-antibodies which recognize several cellular components.
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Autoantibodies against monomeric C-reactive protein (anti-CRP-Ab) observed in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) were suggested to be associated with active LN and a poor response to therapy during short-term...
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The non-histone nuclear protein high mobility group box protein-1 (HMGB1) is typically associated with nucleosomes, but may shuttle between the nucleus and the cytoplasm, and under some conditions also be released extracellularly and participate in...
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by Alisdair M. Boag, Michael R. Christie, Kerry A. McLaughlin, Harriet M.
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MHC, especially HLA-DR3 and HLA-DR2, is one of the most important genetic susceptibility regions for systemic lupus erythematosus.
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Hospital for Special Surgery investigators have identified multiple clinical and biologic markers that correlate with adverse pregnancies in women with lupus, including, most recently, the activation of complement, a series of proteins that protect...
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by Jing Huang, Sha-sha Han, Dan-dan Qin, Li-hua Wu, Yan Song, Feng Yu, Su-xia Wang, Gang Liu, Ming-hui Zhao Objective The aim of this study was to evaluate renal arteriosclerotic lesions in patients with lupus nephritis and investigate their...
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Int J Mol Sci. 2015 Jun 9;16(6):13084-105. doi: 10.3390/ijms160613084. Research Support, Non-U.S. Gov't; Review
Gilbert C FAURE's insight:
Abstract
Toll-like receptors (TLRs) are a large family of pattern recognition receptors. TLR signals are involved in the pathogenesis of systemic lupus erythematosus. Mouse and human B cells constitutively express most TLRs. Many B cell subpopulations are highly responsive to certain TLRligation, including B-1 B cells, transitional B cells, marginal zone B cells, germinal center B cell and memory B cells. The B cell-intrinsic TLRsignals play critical roles during lupus process. In this review, roles of B cell-intrinsic TLR2, 4, 7, 8 and 9 signals are discussed during lupus pathogenesis in both mouse model and patients. Moreover, mechanisms underlying TLR ligation-triggered B cell activation and signaling pathways are highlighted.
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