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Th17-lineage cells in pulmonary sarcoidosis and L öfgren's syndrome: Friend or foe?
Th17-lineage cells in pulmonary sarcoidosis and Löfgren's syndrome: Friend or foe? J Autoimmun. 2018 Jan 05;: Authors: Miedema JR, Kaiser Y, Broos CE, Wijsenbeek MS, Grunewald J, Kool M Abstract Sarcoidosis, a multisystem granulomatous disorder, has historically been classified as Th1-driven disease. However, increasing data demonstrate a key role of Th17-cell plasticity in granuloma formation and maintenance. In Löfgren's syndrome (LS), an acute and distinct phenotype of sarcoidosis with a favorable outcome, differences in Th17-lineage cell subsets, cytokine expression and T-cell suppressiv...
Source: Journal of Autoimmunity - January 5, 2018 Category: Allergy & Immunology Authors: Miedema JR, Kaiser Y, Broos CE, Wijsenbeek MS, Grunewald J, Kool M Tags: J Autoimmun Source Type: research

Identification of non-HLA genes associated with development of islet autoimmunity and type 1 diabetes in the prospective TEDDY cohort.
In this study, 5806 subjects from the TEDDY (The Environmental Determinants of Diabetes in the Young) study, an international prospective cohort study, were genotyped for 176,586 SNPs on the ImmunoChip. Cox proportional hazards analyses were performed to discover the SNPs associated with the risk for IA, T1D, or both. Three regions were associated with the risk of developing any persistent confirmed islet autoantibody: one known region near SH2B3 (HR = 1.35, p = 3.58 × 10-7) with Bonferroni-corrected significance and another known region near PTPN22 (HR = 1.46, p = 2.17 × 10-6) and one n...
Source: Journal of Autoimmunity - January 5, 2018 Category: Allergy & Immunology Authors: Sharma A, Liu X, Hadley D, Hagopian W, Chen WM, Onengut-Gumuscu S, Törn C, Steck AK, Frohnert BI, Rewers M, Ziegler AG, Lernmark Å, Toppari J, Krischer JP, Akolkar B, Rich SS, She JX, TEDDY Study Group Tags: J Autoimmun Source Type: research

CD8+ T cells and IFN- γ induce autoimmune myelofibrosis in mice.
In conclusion, our results demonstrate that CD8+ T cells and IFN-γ are associated with autoimmune myelofibrosis, a finding that may allow targeting of CD8+ T cells and IFN-γ as a therapeutic targets. PMID: 29307587 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - January 4, 2018 Category: Allergy & Immunology Authors: Yao Y, Li L, Yang SH, Gao CY, Liao LH, Xie YQ, Yin XY, Yang YQ, Fei YY, Lian ZX Tags: J Autoimmun Source Type: research

Autoantibodies against podocytic UCHL1 are associated with idiopathic nephrotic syndrome relapses and induce proteinuria in mice.
es G Abstract Idiopathic steroid sensitive nephrotic syndrome (INS), the most frequent childhood nephropathy, is thought to be mediated by a circulating soluble factor that reversibly affects the renal protein sieving. The efficiency of rituximab therapy recently highlighted the involvement of B cells. Here we studied the involvement of a specific immunoglobulin G (IgG) in the disease. After plasma fractionation by size exclusion chromatography, a detachment of cultured podocyte was observed with one IgG-containing fraction from 47% patients in relapse, 9% of patients in remission and 0% of controls. Podocyte prot...
Source: Journal of Autoimmunity - January 4, 2018 Category: Allergy & Immunology Authors: Jamin A, Berthelot L, Couderc A, Chemouny JM, Boedec E, Dehoux L, Abbad L, Dossier C, Daugas E, Monteiro RC, Deschênes G Tags: J Autoimmun Source Type: research

Pathogenic IgG4 autoantibodies from endemic pemphigus foliaceus recognize a desmoglein-1 conformational epitope.
Abstract Fogo Selvagem (FS), the endemic form of pemphigus foliaceus, is mediated by pathogenic IgG4 autoantibodies against the amino-terminal extracellular cadherin domain of the desmosomal cadherin desmoglein 1 (Dsg1). Here we define the detailed epitopes of these pathogenic antibodies. Proteolytic footprinting showed that IgG4 from 95% of FS donor sera (19/20) recognized a 16-residue peptide (A129LNSMGQDLERPLELR144) from the EC1 domain of Dsg1 that overlaps the binding site for an adhesive-partner desmosomal cadherin molecule. Mutation of Dsg1 residues M133 and Q135 reduced the binding of FS IgG4 autoantibodies...
Source: Journal of Autoimmunity - January 4, 2018 Category: Allergy & Immunology Authors: Evangelista F, Roth AJ, Prisayanh P, Temple BR, Li N, Qian Y, Culton DA, Liu Z, Harrison OJ, Brasch J, Honig B, Shapiro L, Diaz LA Tags: J Autoimmun Source Type: research

Th17 plasticity and its relevance to inflammatory bowel disease.
Abstract It is now clear that previously polarized T cells possess the ability to change their phenotype and repolarize towards different fates. This intrinsic flexibility is commonly referred to as plasticity and is influenced by the cytokine milieu, microbial products and products of metabolism which, in turn, regulate transcription factors and epigenetic machinery in the intestinal lamina propria. The intestinal immune system faces a particularly difficult challenge. It serves to protect the largest mucosal surface against infection and injury while maintaining a state of tolerance towards dietary antigens and ...
Source: Journal of Autoimmunity - December 28, 2017 Category: Allergy & Immunology Authors: Ueno A, Jeffery L, Kobayashi T, Hibi T, Ghosh S, Jijon H Tags: J Autoimmun Source Type: research

A cellular and molecular view of T helper 17  cell plasticity in autoimmunity.
A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. J Autoimmun. 2017 Dec 21;: Authors: Stadhouders R, Lubberts E, Hendriks RW Abstract Since the original identification of the T helper 17 (Th17) subset in 2005, it has become evident that these cells do not only contribute to host defence against pathogens, such as bacteria and fungi, but that they are also critically involved in the pathogenesis of many autoimmune diseases. In contrast to the classic Th1 and Th2 cells, which represent rather stably polarized subsets, Th17 cells display remarkable heterogeneity and ...
Source: Journal of Autoimmunity - December 21, 2017 Category: Allergy & Immunology Authors: Stadhouders R, Lubberts E, Hendriks RW Tags: J Autoimmun Source Type: research

Plasticity and heterogeneity of Th17 in immune-mediated kidney diseases.
Abstract Anti-neutrophil cytoplasmatic antibody (ANCA)-associated glomerulonephritis, anti-glomerular basement membrane (GBM) glomerulonephritis and lupus nephritis are the most common causes of rapid progressive glomerulonephritis (RPGN) in the Western world. These aggressive forms of autoimmune kidney diseases significantly contribute to end-stage renal disease and are associated with high morbidity and mortality. Moreover, patients show significant heterogeneity with respect to clinical outcome and response to therapy. T cell infiltration is a morphological hallmark of RPGN and it is a critical driver of kidney...
Source: Journal of Autoimmunity - December 21, 2017 Category: Allergy & Immunology Authors: Krebs CF, Panzer U Tags: J Autoimmun Source Type: research

Critical role of ROCK2 activity in facilitating mucosal CD4+ T cell activation in inflammatory bowel disease.
In this study, we demonstrated that the levels of ROCK2, but not ROCK1, activity were significantly upregulated in peripheral blood mononuclear cells (PBMC) and inflamed mucosa from IBD patients using a ROCK activity assay, and that ROCK2 activity in intestinal mucosa was positively correlated with disease severity. Stimulation with TNF markedly upregulated ROCK2 activity in IBD CD4+ T cells through NF-κB signaling. Blockade of ROCK2 activity using Slx-2119 significantly suppressed proinflammatory cytokines in inflamed mucosa from IBD patients including IFX-unresponsive CD patients, and inhibited IBD CD4+ T cells to ...
Source: Journal of Autoimmunity - December 19, 2017 Category: Allergy & Immunology Authors: Yang W, Zhou G, Yu T, Chen L, Yu L, Guo Y, Cong Y, Liu Z Tags: J Autoimmun Source Type: research

Tolerogenic Ag-PLG nanoparticles induce tregs to suppress activated diabetogenic CD4 and CD8 T cells.
Abstract Type 1 diabetes (T1D) is mediated by destruction of pancreatic β cells by autoantigen-specific CD4+ and CD8+ T cells, thus the ideal solution for T1D is the restoration of immune tolerance to β cell antigens. We demonstrate the ability of carboxylated 500 nm biodegradable poly(lactide-co-glycolide) (PLG) nanoparticles PLG nanoparticles (either surface coupled with or encapsulating the cognate diabetogenic peptides) to rapidly and efficiently restore tolerance in NOD.SCID recipients of both activated diabetogenic CD4+ BDC2.5 chromagranin A-specific and CD8+ NY8.3 islet-specific glucose-6-pho...
Source: Journal of Autoimmunity - December 16, 2017 Category: Allergy & Immunology Authors: Prasad S, Neef T, Xu D, Podojil JR, Getts DR, Shea LD, Miller SD Tags: J Autoimmun Source Type: research

Molecular mechanisms underpinning T helper 17 cell heterogeneity and functions in rheumatoid arthritis.
Abstract T helper 17 (Th17) cells are important mediators of immune responses against extracellular bacteria and fungi, and as such play critical regulatory roles in maintaining mucosal homeostasis. Conversely, Th17 cells and their effector molecules interleukin 17A (IL-17A), IL-17F, interferon (IFN)γ, tumor necrosis factor (TNF)α, and granulocyte-macrophage colony-stimulating factor (GM-CSF) are implicated in the pathology of rheumatoid arthritis (RA). Interactions between Th17 cells and other immune cells or stromal cells that are present in the synovial tissue during the earliest phases of the disea...
Source: Journal of Autoimmunity - December 15, 2017 Category: Allergy & Immunology Authors: van Hamburg JP, Tas SW Tags: J Autoimmun Source Type: research

Immune responses to peptides containing homocitrulline or citrulline in the DR4-transgenic mouse model of rheumatoid arthritis.
In conclusion, DR4tg mice immunized with HomoCitJED developed immune responses to CitJED, indicating cross-reactivity. CitJED immune responses were dependent on the SE. HomoCitJED responses occurred in the absence of the SE (B6 mice); however, they developed earlier in DR4tg SE-expressing mice. PMID: 29242008 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - December 11, 2017 Category: Allergy & Immunology Authors: Lac P, Saunders S, Tutunea-Fatan E, Barra L, Bell DA, Cairns E Tags: J Autoimmun Source Type: research

Activation of thyroid antigen-reactive B cells in recent onset autoimmune thyroid disease patients.
In this study, we analyzed the phenotype of thyroid antigen-reactive B cells in the peripheral blood of recent onset and long standing AITD patients. We found that in recent onset patients thyroid antigen-reactive B cells in blood no longer appear anergic, rather they express CD86, a marker of activation. This likely reflects activation of these cells leading to their production of autoantibodies. Hence, this study reports the early loss of anergy in thyroid antigen-reactive B cells, an event that contributes to development of AITD. PMID: 29233566 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - December 9, 2017 Category: Allergy & Immunology Authors: Smith MJ, Rihanek M, Coleman BM, Gottlieb PA, Sarapura VD, Cambier JC Tags: J Autoimmun Source Type: research

Allele-specific methylation of type 1 diabetes susceptibility genes.
Abstract The susceptibility to autoimmune diseases is influenced by genes encoding major histocompatibility complex (MHC) proteins. By examining the epigenetic methylation maps of cord blood samples, we found marked differences in the methylation status of CpG sites within the MHC genes (cis-metQTLs) between carriers of the type 1 diabetes risk haplotypes HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and HLA-DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8). These differences were found in children and adults, and were accompanied by reduced HLA-DR protein expression in immune cells with the HLA-DR3-DQ2 haplotype. Extensive cis-m...
Source: Journal of Autoimmunity - December 7, 2017 Category: Allergy & Immunology Authors: Kindt ASD, Fuerst RW, Knoop J, Laimighofer M, Telieps T, Hippich M, Woerheide MA, Wahl S, Wilson R, Sedlmeier EM, Hommel A, Todd JA, Krumsiek J, Ziegler AG, Bonifacio E Tags: J Autoimmun Source Type: research

Innately versatile: γδ17 T cells in inflammatory and autoimmune diseases.
Innately versatile: γδ17 T cells in inflammatory and autoimmune diseases. J Autoimmun. 2017 Dec 01;: Authors: Papotto PH, Reinhardt A, Prinz I, Silva-Santos B Abstract IL-17-producing γδ (γδ17) T cells form a versatile subset of cells that respond rapidly to innate stimuli and support the pro-inflammatory functions of different myeloid and lymphoid lineages, being particularly critical in the early stages of inflammatory and autoimmune responses. In mice, under homeostatic conditions, these innate-like lymphocytes are pre-programmed in the fetal thymus, through...
Source: Journal of Autoimmunity - December 1, 2017 Category: Allergy & Immunology Authors: Papotto PH, Reinhardt A, Prinz I, Silva-Santos B Tags: J Autoimmun Source Type: research

Th17  cells in primary Sjögren's syndrome: Pathogenicity and plasticity.
Th17 cells in primary Sjögren's syndrome: Pathogenicity and plasticity. J Autoimmun. 2017 Nov 27;: Authors: Verstappen GM, Corneth OBJ, Bootsma H, Kroese FGM Abstract Th17 cells play an important physiological role at mucosal barriers, and are involved in inflammatory responses to pathogens. Th17 cells and their signature cytokine IL-17 are also present in salivary gland lesions of primary Sjögren's syndrome (pSS) patients and can be elevated in their peripheral blood. In pSS patients, clear correlations between increased Th17 cell activity and symptoms of the disease hav...
Source: Journal of Autoimmunity - November 27, 2017 Category: Allergy & Immunology Authors: Verstappen GM, Corneth OBJ, Bootsma H, Kroese FGM Tags: J Autoimmun Source Type: research

Excessive interferon- α signaling in autoimmunity alters glycosphingolipid processing in B cells.
Excessive interferon-α signaling in autoimmunity alters glycosphingolipid processing in B cells. J Autoimmun. 2017 Nov 27;: Authors: Tan AH, Sanny A, Ng SW, Ho YS, Basri N, Lee AP, Lam KP Abstract Excessive interferon-α (IFN-α) production by innate immune cells is a hallmark of autoimmune diseases. What other cell type secretes IFN-α and how IFN-α affects immune cell metabolism and homeostasis in autoimmunity are largely unclear. Here, we report that autoimmune B cells, arising from two different B cell-specific genetic lesions in mice, secrete IFN-α. In addition, I...
Source: Journal of Autoimmunity - November 27, 2017 Category: Allergy & Immunology Authors: Tan AH, Sanny A, Ng SW, Ho YS, Basri N, Lee AP, Lam KP Tags: J Autoimmun Source Type: research

Tick-borne diseases and autoimmunity: A comprehensive review.
ya JM Abstract Tick-borne diseases (TBDs) are emerging and reemerging diseases transmitted by ticks, which portray wide heterogeneity and global distribution. TBDs may present acute clinical pictures that resemble those of autoimmune diseases (i.e., musculoskeletal symptoms, cutaneous involvement, neurologic impairment, renal failure, etc.), and in some cases infection is considered a triggering factor for autoimmunity (e.g., rheumatoid arthritis, autoimmune thyroid disease, vasculitides). The clinician should consider TBDs among the differential diagnoses when approaching autoimmune-like signs in areas of tick in...
Source: Journal of Autoimmunity - November 25, 2017 Category: Allergy & Immunology Authors: Rodríguez Y, Rojas M, Gershwin ME, Anaya JM Tags: J Autoimmun Source Type: research

Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in  vivo.
Selective targeting of pro-inflammatory Th1 cells by microRNA-148a-specific antagomirs in vivo. J Autoimmun. 2017 Nov 25;: Authors: Maschmeyer P, Petkau G, Siracusa F, Zimmermann J, Zügel F, Kühl AA, Lehmann K, Schimmelpfennig S, Weber M, Haftmann C, Riedel R, Bardua M, Heinz GA, Tran CL, Hoyer BF, Hiepe F, Herzog S, Wittmann J, Rajewsky N, Melchers FG, Chang HD, Radbruch A, Mashreghi MF Abstract In T lymphocytes, expression of miR-148a is induced by T-bet and Twist1, and is specific for pro-inflammatory Th1 cells. In these cells, miR-148a inhibits the expression of the pro-apoptotic pr...
Source: Journal of Autoimmunity - November 25, 2017 Category: Allergy & Immunology Authors: Maschmeyer P, Petkau G, Siracusa F, Zimmermann J, Zügel F, Kühl AA, Lehmann K, Schimmelpfennig S, Weber M, Haftmann C, Riedel R, Bardua M, Heinz GA, Tran CL, Hoyer BF, Hiepe F, Herzog S, Wittmann J, Rajewsky N, Melchers FG, Chang HD, Radbruch A, Mashreg Tags: J Autoimmun Source Type: research

Decrease of galectin-3 in keratinocytes: A potential diagnostic marker and a critical contributor to the pathogenesis of psoriasis.
We report here that epidermal galectin-3 expression is significantly downregulated in lesional skin, but not in non-lesional skin in psoriasis patients, nor in a group of diseases known as psoriasiform dermatitis clinically and histologically similar to psoriasis. The deficiency of epidermal galectin-3 is sufficient to promote development of psoriatic lesions, as evidenced by more severe skin inflammation in galectin-3 knockout (gal3(-/-)) mice, compared to wild-type mice, after imiquimod treatment, and in skin from gal3(-/-) mice grafted onto wildtype mice. The development of psoriatic-like lesions is attributable to 1) t...
Source: Journal of Autoimmunity - November 20, 2017 Category: Allergy & Immunology Authors: Shi ZR, Tan GZ, Cao CX, Han YF, Meng Z, Man XY, Jiang ZX, Zhang YP, Dang NN, Wei KH, Bu DF, Liu FT, Wang L Tags: J Autoimmun Source Type: research

Signaling via toll-like receptor 4 and CD40 in B cells plays a regulatory role in the pathogenesis of multiple sclerosis through interleukin-10 production.
CONCLUSIONS: Cross-talk between TLR4 and CD40 signaling plays a crucial role in regulating IL-10 production by B cells during MS relapses, which may promote recovery from relapse. CD40 signaling in B cells is involved in the response to interferon-β in MS. Collectively, TLR4 and CD40 signaling in B cells may provide a promising target for MS therapy. PMID: 29146546 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 13, 2017 Category: Allergy & Immunology Authors: Okada Y, Ochi H, Fujii C, Hashi Y, Hamatani M, Ashida S, Kawamura K, Kusaka H, Matsumoto S, Nakagawa M, Mizuno T, Takahashi R, Kondo T Tags: J Autoimmun Source Type: research

A gene module associated with dysregulated TCR signaling pathways in CD4(+) T cell subsets in rheumatoid arthritis.
Abstract We analyzed the transcriptome of detailed CD4(+) T cell subsets including them after abatacept treatment, and examined the difference among CD4(+) T cell subsets and identified gene sets that are closely associated disease activity and abatacept treatment. Seven CD4(+) T cell subsets (naive, Th1, Th17, Th1/17, nonTh1/17, Tfh and Treg) were sorted from PBMCs taken from 10 RA patients and 10 healthy controls, and three RA patients donated samples before and 6 months after abatacept treatment. Paired-end RNA sequencing was performed using HiSeq 2500. A total of 149 samples except for 12 outliers were analyze...
Source: Journal of Autoimmunity - November 13, 2017 Category: Allergy & Immunology Authors: Sumitomo S, Nagafuchi Y, Tsuchida Y, Tsuchiya H, Ota M, Ishigaki K, Nakachi S, Kato R, Sakurai K, Hanata N, Tateishi S, Kanda H, Suzuki A, Kochi Y, Fujio K, Yamamoto K Tags: J Autoimmun Source Type: research

Dominant-negative loss of function arises from a second, more frequent variant within the SAND domain of autoimmune regulator (AIRE).
Abstract A genetic variant in the SAND domain of autoimmune regulator (AIRE), R247C, was identified in a patient with type I diabetes mellitus (T1DM) and his mother with rheumatoid arthritis. In vitro, the variant dominantly inhibited AIRE; however, typical features of Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECED) were not seen in the subjects. Rather, early manifestation of autoimmunity appeared to be dependent on additional genetic factors. On a population level, diverse variants were identified in this region. Surprisingly, many likely pathogenic variants were seen disproporti...
Source: Journal of Autoimmunity - November 9, 2017 Category: Allergy & Immunology Authors: Abbott JK, Huoh YS, Reynolds PR, Yu L, Rewers M, Reddy M, Anderson MS, Hur S, Gelfand EW Tags: J Autoimmun Source Type: research

CCR6 signaling inhibits suppressor function of induced-Treg during gut inflammation.
In conclusion, we have identified a new role of CCR6 signaling in the differentiation of iTregs during inflammation and gut autoimmunity. PMID: 29126851 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 7, 2017 Category: Allergy & Immunology Authors: Kulkarni N, Meitei HT, Sonar SA, Sharma PK, Mujeeb VR, Srivastava S, Boppana R, Lal G Tags: J Autoimmun Source Type: research

Autophagy dysfunction in autoinflammatory diseases.
Abstract Autoinflammatory diseases (AUIDs) are a genetically heterogeneous group of rheumatic diseases characterized by episodic inflammation linked with dysregulated innate immune responses. In this review, we summarize the molecular mechanisms altered by disease-associated variants in several AUIDs, including NOD2-associated diseases, TNF receptor-associated periodic syndrome (TRAPS), familial Mediterranean fever (FMF) and hyperimmunoglobulinemia D and periodic fever syndrome (HIDS), and highlight the roles dysregulated autophagy plays in disease pathogenesis. Autophagy is a conserved eukaryotic pathway for the ...
Source: Journal of Autoimmunity - November 3, 2017 Category: Allergy & Immunology Authors: Hua Y, Shen M, McDonald C, Yao Q Tags: J Autoimmun Source Type: research

CD39 and CD73 activity are protective in a mouse model of antiphospholipid antibody-induced miscarriages.
CONCLUSION: We demonstrate a protective role for CD39 in APS and provide rationale for both the development of endothelial cell-targeted soluble CD39 as a novel therapeutic for APS and analysis of perturbations in the purinergic pathway to explain human disease. PMID: 29103803 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - November 2, 2017 Category: Allergy & Immunology Authors: Samudra AN, Dwyer KM, Selan C, Freddi S, Murray-Segal L, Nikpour M, Hickey MJ, Peter K, Robson SC, Sashindranath M, Cowan PJ, Nandurkar HH Tags: J Autoimmun Source Type: research

"NETtling" the host: Breaking of tolerance in chronic inflammation and chronic infection.
"NETtling" the host: Breaking of tolerance in chronic inflammation and chronic infection. J Autoimmun. 2017 Oct 31;: Authors: Skopelja-Gardner S, Jones JD, Rigby WFC Abstract How and why we break tolerance to self-proteins still remains a largely unanswered question. Neutrophils have been identified as a rich source of autoantigens in a wide array of autoimmune diseases that arise as a consequence of different environmental and genetic factors, e.g. rheumatoid arthritis (RA), lupus, vasculitis, cystic fibrosis (CF) etc. Specifically, neutrophil extracellular trap (NET) formation has been ide...
Source: Journal of Autoimmunity - October 31, 2017 Category: Allergy & Immunology Authors: Skopelja-Gardner S, Jones JD, Rigby WFC Tags: J Autoimmun Source Type: research

Wandering pathways in the regulation of innate immunity and inflammation.
Abstract Tumor-associated macrophages (TAM) have served as a paradigm of cancer-related inflammation. Moreover, investigations on TAM have led to the dissection of macrophage plasticity and polarization and to the discovery and analysis of molecular pathways of innate immunity, in particular cytokines, chemokines and PTX3 as a prototypic fluid phase pattern recognition molecule. Mechanisms of negative regulation are complex and include decoy receptors, receptor antagonists, anti-inflammatory cytokines and the signalling regulator IL-1R8. In this review, topics and open issues in relation to regulation of innate im...
Source: Journal of Autoimmunity - October 24, 2017 Category: Allergy & Immunology Authors: Mantovani A Tags: J Autoimmun Source Type: research

Defective regulation of L1 endogenous retroelements in primary Sjogren's syndrome and systemic lupus erythematosus: Role of methylating enzymes.
CONCLUSION: Our data support a contributory role of altered methylation mechanisms in the pathogenesis of systemic autoimmune disorders and related lymphoproliferative processes and suggest that LSH and DNMT3A should be investigated as candidate upstream mediators of decreased L1 promoter methylation and increased L1 expression. PMID: 29074164 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 23, 2017 Category: Allergy & Immunology Authors: Mavragani CP, Nezos A, Sagalovskiy I, Seshan S, Kirou KA, Crow MK Tags: J Autoimmun Source Type: research

Decreased sensitivity to 1,25-dihydroxyvitamin D3 in T cells from the rheumatoid joint.
Abstract 1,25-dihydroxyvitaminD3 (1,25(OH)2D3), has potent anti-inflammatory effects, including suppression of IL-17 + and IFNγ+ T cells implicated in rheumatoid arthritis (RA), but efficacy at the site of active disease is unclear. To investigate this, T cells from synovial fluid (SF) and paired blood of patients with active RA were studied. 1,25(OH)2D3 had significantly less suppressive effect on Th17 cells (IL-17+IFNγ-) and Th17.1 cells (IL-17+IFNγ+) from SF compared to those from blood, and had no effect on SF CD4(+) or CD8(+) IFNγ+ T cell frequencies. Memory T cells...
Source: Journal of Autoimmunity - October 21, 2017 Category: Allergy & Immunology Authors: Jeffery LE, Henley P, Marium N, Filer A, Sansom DM, Hewison M, Raza K Tags: J Autoimmun Source Type: research

CD4+CD28+KIR+CD11a(hi) T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients.
CONCLUSION: CD4+CD28+KIR+CD11a(hi) T cells are demethylated and characterized by pro-inflammatory epigenetic and transcriptional profiles in lupus. Eliminating these cells or blocking their pro-inflammatory characteristics might present a novel therapeutic approach for lupus. PMID: 29066026 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 20, 2017 Category: Allergy & Immunology Authors: Gensterblum E, Renauer P, Coit P, Strickland FM, Kilian NC, Miller S, Ognenovski M, Wren JD, Tsou PS, Lewis EE, Maksimowicz-McKinnon K, McCune WJ, Richardson BC, Sawalha AH Tags: J Autoimmun Source Type: research

Interferon-beta specific T cells are associated with the development of neutralizing antibodies in interferon-beta treated multiple sclerosis patients.
Abstract Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β. T cell responses were determined by split-well and primary proliferation ...
Source: Journal of Autoimmunity - October 20, 2017 Category: Allergy & Immunology Authors: Kalluri SR, Grummel V, Hracsko Z, Pongratz V, Pernpeintner V, Gasperi C, Buck D, Hemmer B, ABIRISK Consortium Tags: J Autoimmun Source Type: research

NEPHRUTIX: A randomized, double-blind, placebo vs Rituximab-controlled trial assessing T-cell subset changes in Minimal Change Nephrotic Syndrome.
Abstract Minimal-change nephrotic syndrome (MCNS) is an immune-mediated glomerular disease. We have analyzed the modifications on T-cell subsets in twenty-three patients who were highly steroid/calcineurin inhibitor and/or mycophenolate mofetil-dependent for frequently relapsing nephrotic syndrome (FRNS) and who were enrolled in a multicenter, double-blind, randomized, placebo vs Rituximab-controlled trial. Patients with FRNS entered the trial at remission and were randomly assigned to receive either Rituximab or placebo. In both groups, patient blood samples were analyzed at inclusion and then monthly until six m...
Source: Journal of Autoimmunity - October 19, 2017 Category: Allergy & Immunology Authors: Boumediene A, Vachin P, Sendeyo K, Oniszczuk J, Zhang SY, Henique-Greciet C, Pawlak A, Audard V, Ollero M, Guigonis V, Sahali D Tags: J Autoimmun Source Type: research

An intermediate level of CD161 expression defines a novel activated, inflammatory, and pathogenic subset of CD8(+) T cells involved in multiple sclerosis.
We report here that CD8(+)CD161(int) T cells present characteristics of effector cells, up-regulate cell-adhesion molecules and have an increased ability to cross the blood-brain barrier and to secrete IL-17, IFNγ, GM-CSF, and IL-22. We further demonstrate that these cells are recruited and enriched in the CNS of MS subjects where they produce IL-17. In the peripheral blood, RNAseq, RT-PCR, high-throughput TCR repertoire analyses, and flow cytometry confirmed an increased effector and transmigration pattern of these cells in MS patients, with the presence of supernumerary clones compared to healthy controls. Our data...
Source: Journal of Autoimmunity - October 17, 2017 Category: Allergy & Immunology Authors: Nicol B, Salou M, Vogel I, Garcia A, Dugast E, Morille J, Kilens S, Charpentier E, Donnart A, Nedellec S, Jacq-Foucher M, Le Frère F, Wiertlewski S, Bourreille A, Brouard S, Michel L, David L, Gourraud PA, Degauque N, Nicot AB, Berthelot L, Laplaud DA Tags: J Autoimmun Source Type: research

Novel genetic loci associated HLA-B*08:01 positive myasthenia gravis.
m L Abstract OBJECTIVE: To identify potential causative markers involved in the development of early-onset myasthenia gravis (EOMG) in the MHC and non-MHC regions that may interact with the HLA-B*08:01 allele. METHODS: We analyzed 583 MG patients and identified 5 patients homozygous for the disease-associated ancestral haplotype 8.1 (HLA-A*01:01, B*08:01, DRB1*03:01, DQB1*02:01). We also analyzed more than 9000 controls and selected 24 for further investigation. We subsequently conducted a fine mapping analysis through high-throughput sequencing of the MHC region (from upstream of the GPα5 gene to ...
Source: Journal of Autoimmunity - October 13, 2017 Category: Allergy & Immunology Authors: Varade J, Wang N, Lim CK, Zhang T, Zhang Y, Liu X, Piehl F, Matell R, Cao H, Xu X, Hammarström L Tags: J Autoimmun Source Type: research

Impaired anti-inflammatory activity of PPAR γ in the salivary epithelia of Sjögren's syndrome patients imposed by intrinsic NF-κB activation.
Impaired anti-inflammatory activity of PPARγ in the salivary epithelia of Sjögren's syndrome patients imposed by intrinsic NF-κB activation. J Autoimmun. 2017 Oct 12;: Authors: Vakrakou AG, Polyzos A, Kapsogeorgou EK, Thanos D, Manoussakis MN Abstract Sjögren's syndrome (SS) patients manifest inflammation in the salivary glands (SG) and evidence of persistent intrinsic activation of ductal SG epithelial cells (SGEC), demonstrable in non-neoplastic SGEC lines derived from patients (SS-SGEC). The peroxisome-proliferator-activated receptor-γ (PPARγ) mediates important an...
Source: Journal of Autoimmunity - October 12, 2017 Category: Allergy & Immunology Authors: Vakrakou AG, Polyzos A, Kapsogeorgou EK, Thanos D, Manoussakis MN Tags: J Autoimmun Source Type: research

Risk of beta-cell autoimmunity presence for progression to type 1 diabetes: A systematic review and meta-analysis.
CONCLUSION: This study established the association between the seroconversion of islet autoantibodies and T1DM progression in nondiabetic people with or without definite genetic susceptibility, providing further evidence for an extensive application in routine clinical practice to identify individuals at risk of T1DM. PMID: 28988642 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - October 5, 2017 Category: Allergy & Immunology Authors: Ling Q, Lu J, Li J, Xu Q, Zhu D, Bi Y Tags: J Autoimmun Source Type: research

The DNA methylation landscape of CD4(+) T cells in oligoarticular juvenile idiopathic arthritis.
Abstract Juvenile idiopathic arthritis (JIA) is presumed to be driven by an adverse combination of genes and environment. Epigenetic processes, including DNA methylation, act as a conduit through which the environment can regulate gene activity. Altered DNA methylation has been associated with adult autoimmune rheumatic diseases such as rheumatoid arthritis, but studies are lacking for paediatric autoimmune rheumatic diseases including JIA. Here, we performed a genome-scale case-control analysis of CD4(+) T cell DNA methylation from 56 oligoarticular JIA (oJIA) cases and 57 age and sex matched controls using Illum...
Source: Journal of Autoimmunity - September 29, 2017 Category: Allergy & Immunology Authors: Chavez-Valencia RA, Chiaroni-Clarke RC, Martino DJ, Munro JE, Allen RC, Akikusa JD, Ponsonby AL, Craig JM, Saffery R, Ellis JA Tags: J Autoimmun Source Type: research

A T cell-specific deletion of HDAC1 protects against experimental autoimmune encephalomyelitis.
In this study we report that mice with a T cell-specific deletion of HDAC1 (using the Cd4-Cre deleter strain; HDAC1-cKO) were completely resistant to EAE despite the ability of HDAC1cKO CD4(+) T cells to differentiate into Th17 cells. RNA sequencing revealed STAT1 as a prominent upstream regulator of differentially expressed genes in activated HDAC1-cKO CD4(+) T cells and this was accompanied by a strong increase in phosphorylated STAT1 (pSTAT1). This suggests that HDAC1 controls STAT1 activity in activated CD4(+) T cells. Increased pSTAT1 levels correlated with a reduced expression of the chemokine receptors Ccr4 and...
Source: Journal of Autoimmunity - September 27, 2017 Category: Allergy & Immunology Authors: Göschl L, Preglej T, Hamminger P, Bonelli M, Andersen L, Boucheron N, Gülich AF, Müller L, Saferding V, Mufazalov IA, Hirahara K, Seiser C, Matthias P, Penz T, Schuster M, Bock C, Waisman A, Steiner G, Ellmeier W Tags: J Autoimmun Source Type: research

Myelin oligodendrocyte glycoprotein-specific antibodies from multiple sclerosis patients exacerbate disease in a humanized mouse model.
Abstract Myelin oligodendrocyte glycoprotein (MOG) is exposed on the outer surface of the myelin sheath, and as such, represents a possible target antigen for antibodies in multiple sclerosis (MS) and other demyelinating diseases. However, despite extensive analyses, whether MOG-specific antibodies contribute to pathogenesis in human MS remains an area of uncertainty. In the current study we demonstrate that antibodies derived from adult MS patients exacerbate experimental autoimmune encephalomyelitis (EAE) in 'humanized' mice that transgenically express human FcγRs (hFcγRs). Importantly, this exacerba...
Source: Journal of Autoimmunity - September 27, 2017 Category: Allergy & Immunology Authors: Khare P, Challa DK, Devanaboyina SC, Velmurugan R, Hughes S, Greenberg BM, Ober RJ, Ward ES Tags: J Autoimmun Source Type: research

Dimethyl fumarate influences innate and adaptive immunity in multiple sclerosis.
CONCLUSION: This study translates knowledge from in-vitro and animal studies on DMF into the clinical setting. Our data suggest that DMF not only alters lymphocyte composition, but also has profound effects on proliferation and induces oxidative stress in T cells. It also acts on innate immunity by reducing the activation status of antigen presenting cells (APCs) via NFkB and MAPK inactivation. PMID: 28958667 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 25, 2017 Category: Allergy & Immunology Authors: Diebold M, Sievers C, Bantug G, Sanderson N, Kappos L, Kuhle J, Lindberg RLP, Derfuss T Tags: J Autoimmun Source Type: research

Monogenic Hashimoto thyroiditis associated with a variant in the thyroglobulin (TG) gene.
CONCLUSION: We discovered a monogenic form of AITD associated with a splice site variant in the thyroglobulin gene. This finding raises questions about the origins of thyroid autoimmunity; possible explanations include increased immunogenicity of the mutated protein or thyroid toxicity with secondary development of anti-thyroid antibodies. Further study into the effects of this variant on thyroid function and thyroid autoimmunity are warranted. PMID: 28942902 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 21, 2017 Category: Allergy & Immunology Authors: Lo MS, Towne M, VanNoy GE, Brownstein CA, Lane AA, Chatila TA, Agrawal PB Tags: J Autoimmun Source Type: research

Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies.
Gestational respiratory infections interacting with offspring HLA and CTLA-4 modifies incident β-cell autoantibodies. J Autoimmun. 2017 Sep 20;: Authors: Lynch KF, Lee HS, Törn C, Vehik K, Krischer JP, Larsson HE, Haller MJ, Hagopian WA, Rewers MJ, She JX, Simell OG, Toppari J, Ziegler AG, Akolkar B, Hyöty H, Bonifacio E, Lernmark Å, TEDDY Study Group Abstract β-cell autoantibodies against insulin (IAA), GAD65 (GADA) and IA-2 (IA-2A) precede onset of childhood type 1 diabetes (T1D). Incidence of the first appearing β-cell autoantibodies peaks at a young age and is patter...
Source: Journal of Autoimmunity - September 20, 2017 Category: Allergy & Immunology Authors: Lynch KF, Lee HS, Törn C, Vehik K, Krischer JP, Larsson HE, Haller MJ, Hagopian WA, Rewers MJ, She JX, Simell OG, Toppari J, Ziegler AG, Akolkar B, Hyöty H, Bonifacio E, Lernmark Å, TEDDY Study Group Tags: J Autoimmun Source Type: research

Clinical predictors of response and discontinuation of belimumab in patients with systemic lupus erythematosus in real life setting. Results of a large, multicentric, nationwide study.
CONCLUSION: Belimumab is effective and safe when used in clinical practice setting. PMID: 28935492 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 18, 2017 Category: Allergy & Immunology Authors: Iaccarino L, Andreoli L, Bocci EB, Bortoluzzi A, Ceccarelli F, Conti F, De Angelis R, De Marchi G, De Vita S, Di Matteo A, Emmi G, Emmi L, Gatto M, Gerli R, Gerosa M, Govoni M, Larosa M, Meroni PL, Mosca M, Pazzola G, Reggia R, Saccon F, Salvarani C, Tani Tags: J Autoimmun Source Type: research

Paradoxical development of polymyositis-like autoimmunity through augmented expression of autoimmune regulator (AIRE).
We examined the effect of additive expression of human AIRE (huAIRE) in a model of autoimmune diabetes in NOD mice. Unexpectedly, we observed that mice expressing augmented AIRE/Aire developed muscle-specific autoimmunity associated with incomplete maturation of mTECs together with impaired expression of Aire-dependent TRAs. This led to failure of deletion of autoreactive T cells together with dramatically reduced production of regulatory T cells in the thymus. In peripheral APCs, expression of costimulatory molecules was augmented. We suggest that levels of Aire expression need to be tightly controlled for maintenance of ...
Source: Journal of Autoimmunity - September 17, 2017 Category: Allergy & Immunology Authors: Nishijima H, Kajimoto T, Matsuoka Y, Mouri Y, Morimoto J, Matsumoto M, Kawano H, Nishioka Y, Uehara H, Izumi K, Tsuneyama K, Okazaki IM, Okazaki T, Hosomichi K, Shiraki A, Shibutani M, Mitsumori K, Matsumoto M Tags: J Autoimmun Source Type: research

SUMO proteins: Guardians of immune system.
In conclusion, we speculate that targeting SUMOs could represent a new therapeutic strategy against infections and autoimmunity. PMID: 28919255 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 14, 2017 Category: Allergy & Immunology Authors: Adorisio S, Fierabracci A, Muscari I, Liberati AM, Ayroldi E, Migliorati G, Thuy TT, Riccardi C, Delfino DV Tags: J Autoimmun Source Type: research

The differential organogenesis and functionality of two liver-draining lymph nodes in mice.
In conclusion, the portal LN and celiac LN are two independent liver-draining LNs with different organogenesis histories and separate functions in maintaining immune homeostasis in the liver. PMID: 28886898 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - September 5, 2017 Category: Allergy & Immunology Authors: Yu J, Chen Y, Wu Y, Ye L, Lian Z, Wei H, Sun R, Tian Z Tags: J Autoimmun Source Type: research

Identification and phenotyping of circulating autoreactive proteinase 3-specific B cells in patients with PR3-ANCA associated vasculitis and healthy controls.
Abstract OBJECTIVES: To develop a method to detect and phenotype circulating proteinase 3 (PR3)-specific B-cells in patients with PR3-ANCA associated vasculitis (AAV). METHODS: Recombinant human PR3 (rPR3) was tagged with FITC or biotin, and its binding characteristics were studied by flow cytometry using three hybridoma cell lines secreting antibodies (Ab) against human PR3, mouse PR3 (no cross-reactivity with human PR3), and human neutrophil elastase. We measured the proportion of PR3-specific B-cells and studied their surface phenotype in patients with PR3-AAV and healthy controls (HC). RESULTS: Label...
Source: Journal of Autoimmunity - September 1, 2017 Category: Allergy & Immunology Authors: Cornec D, Berti A, Hummel A, Peikert T, Pers JO, Specks U Tags: J Autoimmun Source Type: research

Beh çet Disease serum is immunoreactive to neurofilament medium which share common epitopes to bacterial HSP-65, a putative trigger.
Behçet Disease serum is immunoreactive to neurofilament medium which share common epitopes to bacterial HSP-65, a putative trigger. J Autoimmun. 2017 Aug 24;: Authors: Lule S, Colpak AI, Balci-Peynircioglu B, Gursoy-Ozdemir Y, Peker S, Kalyoncu U, Can A, Tekin N, Demiralp D, Dalkara T Abstract Autoimmune and dysimmune inflammatory mechanisms on a genetically susceptible background are implicated in the etiology of Behçet's Disease (BD). Heat-shock protein-65 (HSP-65) derived from Streptococcus sanguinis was proposed as a triggering factor based on its homology with human HSP-60. However,...
Source: Journal of Autoimmunity - August 24, 2017 Category: Allergy & Immunology Authors: Lule S, Colpak AI, Balci-Peynircioglu B, Gursoy-Ozdemir Y, Peker S, Kalyoncu U, Can A, Tekin N, Demiralp D, Dalkara T Tags: J Autoimmun Source Type: research

Redirecting T cells with Chimeric Antigen Receptor (CAR) for the treatment of childhood acute lymphoblastic leukemia.
We describe and discuss the process of clinical translation, including the design of a cell manufacturing protocol, vector production and regulatory issues. Multiple antigen targeting and combination of CAR T cells with molecular targeted drugs have also been evaluated as latest strategies to prevail over immune-evasion. PMID: 28843422 [PubMed - as supplied by publisher] (Source: Journal of Autoimmunity)
Source: Journal of Autoimmunity - August 23, 2017 Category: Allergy & Immunology Authors: Biondi A, Magnani CF, Tettamanti S, Gaipa G, Biagi E Tags: J Autoimmun Source Type: research