AUTOIMMUNITY

Correspondence Revised 2017 international consensus on ANCA testing in small vessel vasculitis: support from an external quality assessment Sylvia Broeders1, Sylvie Goletti2, Jean-Paul Tomasi2, Carolien Bonroy3, René-Louis Humbel4, Laurence Lutteri5, Sofie Schouwers6, Lieve Van Hoovels7, Martine Vercammen8, Xavier Bossuyt9 Quality of Laboratories, Sciensano, Brussels, Belgium Cliniques Universitaires Saint-Luc, Brussels, Belgium Laboratory Medicine, University Hospitals Gent, Ghent, Belgium BioneXt Lab Leudelange, Grand Duchy of Luxembourg, Leudelange, Luxembourg Department of Clinical Chemistry, University Hospital of Liège, Liège, Belgium Laboratory Medicine, GasthuisZusters Antwerp, Antwerp, Belgium Laboratory Medicine, OLVZ Aalst, Aalst, Belgium Martine Vercammen, Laboratory Medicine, AZ Sint-Jan Brugge, Brugge, Belgium Laboratory Medicine, University Hospitals Leuven and Department of Microbiology and Immunology, Leuven, Belgium Correspondence to Dr Xavier Bossuyt, Laboratory Medicine, University Hospitals Gasthuisberg, Herestraat 49, Leuven 3000, Belgium; xavier.bossuyt{at}uzleuven.be View Full Text Statistics from Altmetric.com We read with great interest the multicentre study of Damoiseaux et al 1–3 on the detection of antineutrophil cytoplasmic antibodies (ANCA). ANCAs are important laboratory markers to support the diagnosis of ANCA-associated small vessel vasculitis (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). Traditionally, laboratories screen for ANCA by indirect immunofluorescence (IIF) and IIF positive samples are further evaluated for antibodies to proteinase 3 (PR3) or myeloperoxidase (MPO) by specific immunoassays. Such diagnostic algorithm is based on an international consensus statement on ANCA testing issued in 1999.4 Over the last two decades, the diagnostic performance of immunoassays has significantly improved. The recent multicentre study showed a … View Full Text Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Copyright information: © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Linked Articles Correspondence response Jan Damoiseaux Annals of the Rheumatic Diseases 2018; 78 e114-e111 Published Online First: 05 Sep 2018. doi: 10.1136/annrheumdis-2018-214243 Read the full text or download the PDF: Subscribe Log in

Pemphigus consists of a group of rare and severe autoimmune blistering diseases mediated
by pathogenic autoantibodies mainly directed against two desmosomal adhesion proteins,
desmoglein (Dsg)1 and Dsg3 (also known as DG1 and DG3), which are present in the skin
and surface-close mucosae.

A group of University of Florida researchers will use a new $5 million grant to develop a “pancreatic islet on a chip” — a platform that will allow them to more efficiently and effectively study Type 1 diabetes and potential treatments for the condition. The scientists aim to develop a device known as a microphysiological system that can provide insight into what triggers the disease and offer a way for them to rapidly and safely test new treatments, the researchers said. In Type 1 diabetes, the immune system goes rogue and kills cells in the pancreas that regulate blood sugar. Islets are the regions of the pancreas that contain insulin-producing cells. The system will harness recent advances in stem cell technology, gene editing and biomedical devices to replicate the conditions in the body that result in Type 1 diabetes. That will give researchers a unique window to study the mechanisms of immune cell destruction caused by Type 1 diabetes, said Cherie Stabler, Ph.D., one of the principal investigators on the grant and a professor in UF’s J. Crayton Pruitt Family department of biomedical engineering.  Without the system, testing new therapies for Type 1 diabetes would cost up to $10 million and require years of clinical trials, the researchers said. Ultimately, researchers will be able to generate human cells with immune characteristics similar to those found in people with Type 1 diabetes. Those cells can then be inserted into customized chip devices to provide what Stabler said is unprecedented insight into cellular interactions. “This work is so exciting, as it integrates technology that was not even possible a few years ago. We hope to leverage this technology to really dive into the mechanisms of disease activation and progression, as well as to efficiently screen novel therapeutics,” Stabler said. The new system will let researchers more effectively study and work on correcting the mechanisms that cause Type 1 diabetes, said Todd Brusko, Ph.D., a principal investigator and associate professor of pathology in the UF College of Medicine who also is associated with the UF Diabetes Institute. That could include studying ways to protect insulin-producing beta cells found in the pancreas or blocking the immune system response that attacks and kills beta cells. “This will be a model system for testing different therapeutic agents without having to wait a decade for clinical trials,” Brusko said. The system being developed will also have some scientific advantages: Starting with self-replicating, undifferentiated stem cells, researchers will be able to derive different cell types that are believed to be important to the disease process in Type 1 diabetes. They can then be combined to create a model of the disease without mixing samples from different patients, Brusko said. Having a system that replicates certain pancreatic cellular functions also solves a significant scientific conundrum. Researchers now are limited to screening patients’ blood for the biological markers of Type 1 diabetes or studying a single point in time using a deceased donor’s pancreas. This prevents researchers from studying factors that initiate the disease or the immune pathways that are activated as the disease progresses, according to Stabler. All of that limits scientists’ ability to generate drugs or interventions that slow or stop Type 1 diabetes. Now, modeling the disease outside of the body and mixing key cellular components will help researchers better understand what is happening in patients, Brusko said. The five-year grant is a multidisciplinary effort that builds on a history of collaboration between the UF Diabetes Institute and the J. Crayton Pruitt Family department of biomedical engineering as well as engineers at the University of Miami. In addition to Stabler and Brusko, other principal investigators include Clayton Mathews, Ph.D., the Sebastian Family Professor for Diabetes Research at the UF Diabetes Institute and a professor in the UF College of Medicine’s department of pathology, immunology and laboratory medicine; and Ashutosh Agarwal, Ph.D., an assistant professor of biomedical engineering at the University of Miami. The grant is a collaborative effort between the Consortium on Modeling Autoimmune Interactions and the Consortium on Human Islet Biometrics, both supported under the National Institutes of Health-supported Human Islet Research Network.

This article describes a protocol for the generation of antigen-specific CD8 T cells, and their expansion in vitro, with the aim of...

Scientists from University Hospital Erlangen, Germany, discovered the 'established' beta-blocker metoprolol blocked the growth of gallstones in mice with the painful condition.

Systemic lupus erythematosus Fatigue in SLE: diagnostic and pathogenic impact of anti-N-methyl-D-aspartate receptor (NMDAR) autoantibodies Andreas Schwarting1,2, Tamara Möckel1, Freya Lütgendorf2, Konstantinos Triantafyllias2, Sophia Grella1, Simone Boedecker1, Arndt Weinmann1, Myriam Meineck1, Clemens Sommer3, Ingrid Schermuly4, Andreas Fellgiebel4, Felix Luessi5, Julia Weinmann-Menke1 Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany Acura Rheumatology Center Rhineland Palatinate, Bad Kreuznach, Germany Institute of Neuropathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany Department of Psychiatry and Psychotherapy, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany Correspondence to Andreas Schwarting, Division of Rheumatology and Clinical Immunology, University Medical Center of the Johannes-Gutenberg University Mainz, Mainz 55131, Germany; schwarting{at}uni-mainz.de Abstract Objectives We explored the impact of circulating anti-N-methyl-D-aspartate receptor (NMDAR) antibodies on the severity of fatigue in patients with systemic lupus erythematosus (SLE). Methods Serum samples of 426 patients with SLE were analysed for the presence of antibodies to the NR2 subunit of the NMDAR. In parallel, the severity of fatigue was determined according to the Fatigue Scale for Motor and Cognitive functions questionnaire. In a subgroup of patients with SLE, the hippocampal volume was correlated with the levels of anti-NR2 antibodies. Isolated immunoglobulin G from patients with anti-NR2 antibodies were used for murine immunohistochemical experiments and functional assays on neuronal cell lines. Treatment effects were studied in 86 patients with lupus under belimumab therapy. Results We found a close correlation between the titre of anti-NR2 antibodies, the severity of fatigue, the clinical disease activity index (Systemic Lupus Erythematosus Disease Activity Index 2000) and anti-double stranded DNA antibodies—independently of the presence of neuropsychiatric lupus manifestations. Pathogenic effects could be demonstrated by (1) detection of anti-NR2 antibodies in the cerebrospinal fluid, (2) in situ binding of anti-NR2 antibodies to NMDAR of the hippocampus area and (3) distinct functional effects in vitro: downregulating the energy metabolism of neuronal cells without enhanced cytotoxicity. Treatment with belimumab for at least 6 months affected both the severity of fatigue and the levels of anti-NR2 antibodies. Conclusion The presence of anti-NR2 antibodies in patients with SLE with fatigue is a helpful diagnostic tool and may offer a major approach in the therapeutic management of this important disabling symptom in patients with SLE. View Full Text Statistics from Altmetric.com View Full Text Footnotes Handling editor Josef S Smolen Contributors AS and JW conceived and supervised the study. AS, AW, JW, SG and MM maintained the SLE database. TM, MM, CS, AF, IS, SG and FL contributed to the acquisition of data. All authors have made substantial contributions to the analysis or interpretation of data and revised the manuscript critically for important intellectual content and approved the version for publication. Funding The Investigator-initiated-study was supported by GSK (data acquisition) and the Deutsche Forschungsgemeinschaft. Competing interests AS, TM, FL, KT, SG, SB, AW, FL, MM, CS, IS and AF have nothing to declare; AS has received speaker fees (less than US$10 000) and grant/research support by AbbVie, Novartis, Roche and GSK; KT has received speaker fees (less than US$10 000) and research support from Pfizer outside the submitted work. Patient and public involvement statement Indirect Patient and Public Involvement. We did not directly include PPI in this study, but the initiative of the study was driven by lupus patients and their representatives. Patient consent for publication Not required. Ethics approval The study protocol was approved by the local ethics committee (Ethics Commission of the State Chamber of Medicine in Rheinland-Pfalz, Mainz, Germany) in adherence to the Declaration of Helsinki. Provenance and peer review Not commissioned; externally peer reviewed. Data sharing statement All data relevant to the study are included in the article or uploaded as supplementary information. Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Copyright information: © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Read the full text or download the PDF: Subscribe Log in

Abstract Phosphatidylinositol 3 kinases (PI3K) are a family of lipid kinases that are activated by a variety of cell‐surface receptors, and regulate a wide range of downstream readouts affecting ce...

UC San Diego School of Medicine has been awarded $9 million to fund research projects using human pluripotent stem cells, CRISPR and human organoids to dissect beta cell defects and create a human cell model of type 1 diabetes aimed at identifying the cellular actions leading to disease onset.

Premature ovarian insufficiency (POI) is a hypergonadotropic hypogonadism condition which is characterised by impairment of ovarian function on a...

Abstract Insulin deficiency in type 1 diabetes (T1D) is generally considered a consequence of immune‐mediated specific beta‐cell loss. Since healthy pancreatic islets consist of ~65% beta cells, th...

Toll-like receptors play an important role in host defense. TLR-7 recognizes viral ssRNA, but also plays a role in the development of systemic lupus erythematosus (SLE). Genetic ablation of a similar receptor, TLR-9, results in opposite effects, with severe disease and kidney involvement.

Background The relationship between the risk of celiac disease and both the age at which gluten is introduced to a child’s diet and a child’s early dietary pattern is unclear. Methods We randomly a...

Letter Idiopathic inflammatory myopathies and antisynthetase syndrome: contribution of antisynthetase antibodies to improve current classification criteria Martin Greco1, María Jesus García de Yébenes2, Inmaculada Alarcón3, Anahy María Brandy-García4, Íñigo Rúa-Figueroa1, Estibaliz Loza2, Loreto Carmona2 Rheumatology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain Instituto de Salud Musculoesquelética, Madrid, Spain Biochemical Department, Autoimmunity Laboratory, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria, Spain Rheumatology Department, Hospital Universitario Central de Asturias, Oviedo, Spain Correspondence to Dr Martin Greco, Rheumatology Department, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas de Gran Canaria 35010, Spain; martin-greco{at}hotmail.com View Full Text Statistics from Altmetric.com The presence of muscle weakness and anti-Jo1 anti-aminoacyl transfer RNA synthetase (ARS) autoantibodies are evaluated in the new European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) proposed classification criteria for adult and juvenile idiopathic inflammatory myopathies (IIM), as well as in the Solomon proposed criteria for antisynthetase syndrome (ASSD) diagnosis.1 2 That favours an overlapping in both criteria fulfilment; however, ASSD is not considered among the IIM subgroups classification. Anti-Jo1 ARS positivity is the highest weighted criterion in the EULAR/ACR criteria. Furthermore, anti-PL7 and anti-PL12 ARS were found to be strongly associated with IIM during the criteria development; however, the low number of observations limited their reliability analysis, and they were not finally included.1 3 Anti-EJ, anti-OJ and other ARS were not considered at all due to the limited availability of detection methods at the start of the criteria development.3 On the other hand, any ARS positivity is considered in Solomon’s criteria. Thus, according to other authors, we purpose that IIM and ASSD classification criteria … View Full Text Request Permissions If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways. Copyright information: © Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ. Read the full text or download the PDF: Subscribe Log in