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Rescooped by
Gilbert C FAURE
from Cytokines et Chimiokines
May 30, 2017 9:07 AM
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The integrin α9β1 is a key receptor involved in the development of autoimmune diseases. However, the detailed mechanism for the association of α9β1 integrin with its ligands remains unclear. In this study, we introduce XCL1/lymphotactin, a member of the chemokine family, as a novel ligand for α9 integrin. Using α9 integrin–overexpressing NIH3T3 cells and endogenously α9 integrin–expressing human rhabdomyosarcoma cells, the interaction between XCL1 and α9 integrin was confirmed by pull-down assays. XCL1 enhanced α9 integrin–dependent cell migration of these cells, thus acting on α9 integrin as a chemoattractant. We also analyzed the in vivo function of XCL1 in the development of anti-type II collagen Ab–induced inflammatory arthritis (CAIA) in BALB/c mice and experimental autoimmune encephalomyelitis in C57BL/6 mice, because α9 integrin is involved in these autoimmune disease models. In CAIA, recombinant XCL1 aggravated the disease and this exacerbation was inhibited by an anti-α9 integrin Ab. An XCL1-neutralizing Ab produced in this study also ameliorated CAIA. Furthermore, the XCL1-neutralizing Ab abrogated the disease progression in experimental autoimmune encephalomyelitis. Therefore, to our knowledge this study provides the first in vitro and in vivo evidence that the interaction between XCL1 and α9 integrin has an important role for autoimmune diseases.
Via Société Francaise d'Immunologie
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Suggested by
Société Francaise d'Immunologie
May 27, 2017 2:28 PM
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In NOD mice, CD11c+ cells increase greatly with islet inflammation and contribute to autoimmune destruction of pancreatic β cells. In this study, we investigated their origin and mechanism of recruitment. CD11c+ cells in inflamed islets resembled classical dendritic cells based on their transcriptional profile. However, the majority of these cells were not from the Zbtb46-dependent dendritic-cell lineage. Instead, monocyte precursors could give rise to CD11c+ cells in inflamed islets. Chemokines Ccl5 and Ccl8 were persistently elevated in inflamed islets and the influx of CD11c+ cells was partially dependent on their receptor Ccr5. Treatment with islet Ag-specific regulatory T cells led to a marked decrease of Ccl5 and Ccl8, and a reduction of monocyte recruitment. These results implicate a monocytic origin of CD11c+ cells in inflamed islets and suggest that therapeutic regulatory T cells directly or indirectly regulate their influx by altering the chemotactic milieu in the islets.
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Suggested by
Société Francaise d'Immunologie
May 26, 2017 9:58 AM
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Objective: To identify a genetic cause of early‐onset systemic lupus erythematosus (SLE) in a large consanguineous family from Turkey and to study the mechanisms of disease.Methods: We performe
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Scooped by
Gilbert C FAURE
May 25, 2017 9:59 AM
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It is well established that therapeutic injection of insulin into type 1 diabetic patients leads to the generation of insulin antibodies in rare cases, such an
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
May 23, 2017 4:28 AM
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Publication date: 2016
Source:Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring, Volume 3
Author(s): Cassandra A. DeMarshall, Eric P. Nagele, Abhirup Sarkar, Nimish K. Acharya, George Godsey, Eric L. Goldwaser, Mary Kosciuk, Umashanger Thayasivam, Min Han, Benjamin Belinka, Robert G. Nagele
Introduction There is an urgent need to identify biomarkers that can accurately detect and diagnose Alzheimer's disease (AD). Autoantibodies are abundant and ubiquitous in human sera and have been previously demonstrated as disease-specific biomarkers capable of accurately diagnosing mild-moderate stages of AD and Parkinson's disease. Methods Sera from 236 subjects, including 50 mild cognitive impairment (MCI) subjects with confirmed low CSF Aβ42 levels, were screened with human protein microarrays to identify potential biomarkers for MCI. Autoantibody biomarker performance was evaluated using Random Forest and Receiver Operating Characteristic curves. Results Autoantibody biomarkers can differentiate MCI patients from age-matched and gender-matched controls with an overall accuracy, sensitivity, and specificity of 100.0%. They were also capable of differentiating MCI patients from those with mild-moderate AD and other neurologic and non-neurologic controls with high accuracy. Discussion Autoantibodies can be used as noninvasive and effective blood-based biomarkers for early diagnosis and staging of AD.
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Scooped by
Gilbert C FAURE
May 22, 2017 9:15 AM
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B cell depletion with rituximab (RTX) is approved for treatment of rheumatoid arthritis (RA) and ANCA-associated vasculitides (AAV). Recently, RTX has been shown to be effective in AAV maintenance therapy, but an optimal RTX treatment schedule is unknown and the time to B cell repopulation after RTX has not been studied. Retrospective single-center analysis of B cell repopulation in patients with AAV, RA or connective tissue disease (CTD) treated with RTX. Beginning B cell repopulation within the first year after RTX treatment was observed in 93% of RA and 88% of CTD patients. Only 10% of patients with granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) and no patient with eosinophilic granulomatosis with polyangiitis (EGPA) showed B cell repopulation within this time. Median time of B cell depletion was 26 months in GPA/MPA, and 21 months in EGPA compared to 9 months in RA, and 8 months in CTD (p < 0.0001). In 25 AAV-patients B cell depletion lasted for at least 44 months. There was a significant decline in serum immunoglobulin concentrations in GPA/MPA patients, but not in patients with RA or CTD. Significantly more GPA/MPA patients developed hygogammaglobulinemia (IgG <7 g/L) compared to patients with RA or CTD. In contrast to RA and CTD, in AAV RTX induces long-lasting depletion of B cells that is associated with decreased antibody production. This observation points toward potential defects in the B cell compartment in AAV that are unmasked by immunosuppressive treatment and has important implications for the design of maintenance treatment schedules using RTX.
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Scooped by
Gilbert C FAURE
May 19, 2017 2:52 PM
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This presentation offers an educational overview of autoimmune central nervous system (CNS) disorders, evaluations (including antibody testing), and treatments. Learning Objectives [...]
Narcolepsy is a sleep disorder characterised by loss of hypothalamic hypocretin (orexin)
neurons. The prevalence of narcolepsy is about 30 per 100 000 people, and typical
age at onset is 12–16 years. Narcolepsy is strongly associated with the HLA-DQB1*06:02
genotype, and has been thought of as an immune-mediated disease. Other risk genes,
such as T-cell-receptor α chain and purinergic receptor subtype 2Y11, are also implicated.
Interest in narcolepsy has increased since the epidemiological observations that H1N1
infection and vaccination are potential triggering factors, and an increase in the
incidence of narcolepsy after the pandemic AS03 adjuvanted H1N1 vaccination in 2010
from Sweden and Finland supports the immune-mediated pathogenesis.
Via Krishan Maggon
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Scooped by
Gilbert C FAURE
May 16, 2017 5:13 AM
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Scooped by
Gilbert C FAURE
May 16, 2017 5:09 AM
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Background: Antiphospholipid syndrome is characterized by recurrent thrombosis and gestational morbidity in patients with antiphospholipid autoantibodies (aPLs). Predictive value of the presence of aPLs is low, and new markers are necessary to identify aPL carriers at higher risk and take preventive measures on them. The presence of circulating immune complexes of IgA bound to β2-glycoprotein I (B2A-CIC) has been associated with occurrence of acute thrombotic events. In this work we study its possible predictive value for the appearance of acute thrombotic events in patients who are going to undergo transplant surgery, a well-known trigger of acute thrombotic events in aPL carriers.
Methods: We performed a follow-up study based on the Magnum 12+12 Cohort of patients who received a kidney transplant (n=1339). Three groups were established: group 1 patients who were positive for IgA anti-β2-glycoprotein I (aB2GP1) and B2A-CIC (n=125); group 2 patients who were positive only for IgA aB2GP1 (n=240); and control group, patients who were negative for IgA aB2GP1 (n=974). Levels of autoantibodies and B2A-CIC were quantified immediately before the transplant surgery and patients were followed up for 6 months.
Results: In group 1, 46.4% of patients experienced any type of thrombosis versus 10.4% in group 2 ( P <0.001) and 8.6% in the control group ( P <0.001). The incidence of graft thrombosis in group 1 (31.2%) was significantly higher than that observed in group 2 (3.3%, P <0.001) and the control group (2.6%, P <0.001). In a multivariate analysis, the presence of B2A-CIC was an independent variable to experience any type of posttransplant thrombosis (hazard ratio, 6.72; 95% confidence interval, 4.81–9.37) and, prominently, for graft thrombosis (hazard ratio, 14.75; 95% confidence interval, 9.11–23.89). No significant differences were found between B2A-CIC–negative and control group patients.
Conclusions: The presence of B2A-CIC is a predictor of acute thrombotic events. Patients who were positive for IgA aB2GP1 only are at risk of experiencing thrombosis if they are B2A-CIC positive. If they are B2A-CIC–negative patients, they have the same risk as the control group. Treatments to prevent acute thrombotic events should focus on B2A-CIC–positive patients.
# Clinical Perspective {#article-title-34}
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Scooped by
Gilbert C FAURE
May 16, 2017 2:26 AM
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There is now a consensus on the need to provide healthcare, before and during pregnancy, to women at high
risks of APS related obstetric complications diagnosed based ..
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Scooped by
Gilbert C FAURE
May 14, 2017 12:36 PM
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Cellular and Molecular Immunology aims to report the dynamic progress being made in China and abroad in immunological research, and welcomes high-quality Research Articles, Reviews and Brief Reports across a broad range of topics including, but not limited to, clinical immunology, comparative immunology, immunobiology, immunogenetics, immunological techniques, immunopathology, immunopharmacology, infection immunology, neuroimmunology, transplantation immunology, tumor immunology, and veterinary immunology.
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Suggested by
Société Francaise d'Immunologie
May 30, 2017 6:32 AM
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The BANK1 SLE-risk variants are associated with alterations in peripheral B cell signaling and development in humans
Elizabeth M. Dam
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Suggested by
Société Francaise d'Immunologie
May 27, 2017 2:28 PM
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Objective. To determine the function and serum levels of soluble forms of programmed death‐1 (sPD‐1) and its ligand of PD‐L2 (sPD‐L2) in patients with systemic sclerosis (SSc).Methods. The seru
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Scooped by
Gilbert C FAURE
May 25, 2017 1:49 PM
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Antinuclear antibodies (ANAs) are a diverse group of autoantibodies that recognize nuclear macromolecules and their complexes. ANAs represent key biomarkers in the evaluation of rheumatic diseases, most prominently systemic lupus erythematosus (SLE), and ANA testing is commonly performed in the clinical setting. In addition, ANA testing is now used to assess eligibility for participation in clinical trials of new therapeutic agents for SLE. ANAs can be assayed by various techniques, with the fluorescent ANA assay often viewed as the gold standard. Whereas a positive ANA test represents a classification criterion for SLE, up to 20–30% of the healthy population, depending on the assay used, is positive for an ANA, complicating the use of this test for diagnosis or the detection of preclinical autoimmunity. Furthermore, ANAs might be expressed in SLE less commonly than often thought. This Perspectives article discusses important questions about the use of ANA testing in both the clinical and research settings.
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Scooped by
Gilbert C FAURE
May 25, 2017 1:46 AM
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B lymphocytes play a key role in type 1 diabetes (T1D) development by serving as a subset of APCs preferentially supporting the expansion of autoreactive pathogenic T cells. As a result of their pathogenic importance, B lymphocyte–targeted therapies have received considerable interest as potential T1D interventions. Unfortunately, the B lymphocyte–directed T1D interventions tested to date failed to halt β cell demise. IgG autoantibodies marking humans at future risk for T1D indicate that B lymphocytes producing them have undergone the affinity-maturation processes of class switch recombination and, possibly, somatic hypermutation. This study found that CRISPR/Cas9-mediated ablation of the activation-induced cytidine deaminase gene required for class switch recombination/somatic hypermutation induction inhibits T1D development in the NOD mouse model. The activation-induced cytidine deaminase protein induces genome-wide DNA breaks that, if not repaired through RAD51-mediated homologous recombination, result in B lymphocyte death. Treatment with the RAD51 inhibitor 4,4′-diisothiocyanatostilbene-2, 2′-disulfonic acid also strongly inhibited T1D development in NOD mice. The genetic and small molecule–targeting approaches expanded CD73+ B lymphocytes that exert regulatory activity suppressing diabetogenic T cell responses. Hence, an initial CRISPR/Cas9-mediated genetic modification approach has identified the AID/RAD51 axis as a target for a potentially clinically translatable pharmacological approach that can block T1D development by converting B lymphocytes to a disease-inhibitory CD73+ regulatory state.
This article is featured in In This Issue , p.[4181][1]
[1]: /lookup/volpage/198/4181
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Suggested by
Société Francaise d'Immunologie
May 23, 2017 11:25 AM
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ABSTRACT: Hyper-elevated immune response of FcGRIIb−/− mice, a lupus model with an inhibitory-signal
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Scooped by
Gilbert C FAURE
May 23, 2017 4:27 AM
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EpiGentek, a Farmingdale, NY-based biotech firm specializing in epigenetic research products expands their portfolio of histone modification assays with the release of a series of ELISA-like kits that provide a simple and fast method for detecting circulating histone modifications, including the first commercially available multiplex kit for high-throughput measurement of circulating modified histone H3, directly from plasma or serum. Abnormal histone modification patterns have bee
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Scooped by
Gilbert C FAURE
May 22, 2017 1:45 AM
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Autoantibodies (AAbs) against 4 glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic (cancer-associated retinopathy, CAR) and non-paraneoplastic autoimmune retinopathies as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal autoantibodies. In this review we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases. There are multiple mechanisms responsible for antibody generation, including the innate anti-microbial response, anti-tumor response, or autoimmune response against released self-antigens from damaged, inflamed tissue. Autoantibodies against enolase, GADPH, and aldolase exist in a single patient in elevated titers, suggesting their participation in pathogenicity. The lack of restriction of AAbs to one disease may be related to an increased expression of glycolytic enzymes in various metabolically active tissues that triggers an autoimmune response and generation AAbs with the same specificity in several chronic and autoimmune conditions. In CAR, the importance of serum anti-glycolytic enzyme AAbs had been previously dismissed, but then the retina may be without pathological consequence until a failure of the blood-retinal barrier function, which would allow pathogenic AAbs access to their retinal targets, ultimately leading to damaging effects.
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Scooped by
Gilbert C FAURE
May 17, 2017 9:00 AM
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Wieslab Analys �gs av Euro-Diagnostica, som producerar och s�ljer diagnostiska kit.
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Scooped by
Gilbert C FAURE
May 16, 2017 5:13 AM
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Age-associated B cells (ABCs) were discovered in 2011 to be phenotypically and functionally unique cells common in the spleen, blood, and bone marrow. Howe
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Scooped by
Gilbert C FAURE
May 16, 2017 5:10 AM
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TMA-funded research fellow Xavier Suárez-Calvet, PhD is putting together pieces of the puzzle of dermatomyositis that may someday lead to more effective treatments for this rare autoimmune disease of the muscles.
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Scooped by
Gilbert C FAURE
May 16, 2017 5:08 AM
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P2X7 receptor (P2X7R), trigger of acute inflammatory responses via the NLRP3 inflammasome, is hyperfunctioning in patients with Sjogren Syndrome (SS), where it stimulates IL‐18 production. Som
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Scooped by
Gilbert C FAURE
May 15, 2017 3:01 PM
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Pemphigus is an autoimmune disorder characterized by blisters in the oral mucosa and epidermis.
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