Auto- Immunity Highlights

Special conditions associated with laboratory autoimmune testing are not well compatible with recent developments in regulatory frameworks such as EN/ISO 15189 accreditation or in vitro diagnostic medical device regulation (IVD-R). In addition, international recommendations, guidelines and disease criteria are poorly defined with respect to requirements on autoantibody testing. Laboratory specialists from Austria, Belgium, Croatia, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Norway, Poland, Portugal, South Africa, Spain, Sweden, Switzerland, and The Netherlands collected information, reported national experience, and identified quality issues in relation to autoantibody testing that require consensus on interpretation of the regulatory frameworks and guidelines...

Unlike in other autoimmune liver diseases such as autoimmune hepatitis and primary biliary cholangitis, the role and nature of autoantigenic targets in primary sclerosing cholangitis (PSC), a progressive, chronic, immune-mediated, life threatening, genetically predisposed, cholestatic liver illness, is poorly elucidated. Although anti-neutrophil cytoplasmic antibodies (ANCA) have been associated with the occurrence of PSC, their corresponding targets have not yet been identified entirely. Genome-wide association studies revealed a significant number of immune-related and even disease-modifying susceptibility loci for PSC...

BACKGROUND: β2-Glycoprotein I (β2GPI) represents the major antigenic target for antiphospholipid antibodies (aPL), with domain 1 (D1) being identified as a risk factor for thrombosis and pregnancy complications in APS. We aimed to analyse the ability of aPL, and particularly anti-D1 β2GPI, to stimulate prothrombotic and proinflammatory activity of immune cells in vitro. METHODS: Peripheral blood mononuclear cells (PBMCs) from 11 healthy individuals were incubated with: (1) "anti-D1(+)"-pooled plasma derived from patients suspected of having APS contained anticardiolipin antibodies (aCL), lupus anticoagulant (LA), anti-β2GPI and anti-D1 β2GPI; (2) "anti-D1(-)"-pooled plasma from patients suspected of having APS contained aCL, LA, anti-β2GPI, and negative for anti-D1 β2GPI; (3) "seronegative"-negative for aPL...

Standardisation of immuno-assays for autoantibodies is a major challenge. Although multiple organisations participate in the generation of internationally accepted standards, adequate standardisation of assays has not yet been achieved. Harmonisation may offer an alternative approach to better align requesting, testing, reporting and interpretation of autoimmune diagnostics. The European Autoimmunity Standardisation Initiative (EASI) was founded to facilitate both standardisation as well as harmonisation of autoantibody tests, but over the years the focus has drifted away from standardisation in favour of harmonisation...

The discovery and initial characterization 20 years ago of antinuclear autoantibodies (ANAs) presenting a dense fine speckled (DFS) nuclear pattern with strong staining of mitotic chromosomes, detected by indirect immunofluorescence assay in HEp-2 cells (HEp-2 IIFA test), has transformed our view on ANAs. Traditionally, ANAs have been considered as reporters of abnormal immunological events associated with the onset and progression of systemic autoimmune rheumatic diseases (SARD), also called ANA-associated rheumatic diseases (AARD), as well as clinical biomarkers for the differential diagnosis of these diseases...

Recently, several autoimmune neurological diseases have been defined by the presence of autoantibodies against different antigens of the nervous system. These autoantibodies have been demonstrated to be specific and useful biomarkers, and most of them are also pathogenic. These aspects have increased the value of autoantibodies in neurological practice, as they enable to establish more accurate diagnosis and to better understand the underlying mechanisms of the autoimmune neurological diseases when they are compared to those lacking them...

Receptor autoimmunity is one of the ways in which autoimmune diseases appear in humans. Graves' disease, myasthenia gravis, idiopathic membranous nephropathy, and autoimmune acute encephalitis are the major autoimmune diseases belonging to this particular group. Receptor autoimmune disease are dependent on the presence of autoantibodies directed against cell-surface antigens, namely TSH receptor in thyrocytes, acetylcholine receptor in neuromuscular junction, phospholipase 2 receptor in podocytes, and NMDA receptor in cortical neurons...

Background: Multiple sclerosis is an immune mediated disease targeting the central nervous system. Association of non-human leukocyte antigen gene, CD58 , with multiple sclerosis has been reported in several populations but is unclear among Southeast Asians. This pilot study was conducted to explore the association between CD58 polymorphism and multiple sclerosis among the Malay population in Malaysia. Methods: Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals...

Background: Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/MS) is an incapacitating chronic disease that dramatically compromise the life quality. The CFS/ME pathogenesis is multifactorial, and it is believed that immunological, metabolic and environmental factors play a role. It is well documented an increased activity of Human endogenous retroviruses (HERVs) from different families in autoimmune and neurological diseases, making these elements good candidates for biomarkers or even triggers for such diseases...

Background: The human monoclonal autoantibody K1-70™ binds to the TSH receptor (TSHR) with high affinity and blocks TSHR cyclic AMP stimulation by TSH and thyroid stimulating autoantibodies. Methods: The preclinical toxicology assessment following weekly intravenous (IV) or intramuscular (IM) administration of K1-70™ in rats and cynomolgus monkeys for 29 days was carried out. An assessment of delayed onset toxicity and/or reversibility of toxicity was made during a further 4 week treatment free period...

Background: Anti-mitochondria autoantibodies (AMA) occur in > 95% primary biliary cholangitis (PBC) patients. Biochemically normal AMA-positive (BN/AMA+) individuals, occasionally noticed by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed in AMA-specific assays, may represent early stages of PBC. The Enhanced Liver Fibrosis (ELF) score is a surrogate marker for liver fibrosis. This prospective study investigated the ELF score in BN/AMA+ individuals and PBC patients, considering autoantibody avidity and serum levels along the years...

Background: Antiphospholipid syndrome (APS) is an autoimmune disease characterized by the occurrence of venous and/or arterial thrombosis, and the detection of circulating antiphospholipid antibodies. The classification criteria for definite APS are actually met when at least one clinical criterion (thrombosis or pregnancy morbidity) is present in association of one laboratory criterion (LAC, aCL antibody or aβ2GPI antibody present on two or more occasions, at least 12 weeks a part), and thrombosis should be confirmed by objective validated criteria...

Granulomatosis with polyangiitis (GPA) is a systemic vasculitis with a potential to involve any organ system. It remains an important cause of kidney related morbidity and mortality. Early diagnosis can be difficult and requires high index of suspicion in all patients, but especially in cases with atypical presentation. We report a case with GPA, which was diagnosed only after new and advancing symptoms belied the original diagnosis of bilateral facial palsy and aortic mural thrombus.

Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system characterized by focal or diffuse inflammation, demyelination, axonal loss and neurodegeneration. Brain atrophy can be seen in the earliest stages of MS, progresses faster compared to healthy adults, and is a reliable predictor of future physical and cognitive disability. In addition, it is widely accepted to be a valid, sensitive and reproducible measure of neurodegeneration in MS. Reducing the rate of brain atrophy has only recently been incorporated as a critical endpoint into the clinical trials of new or emerging disease modifying drugs (DMDs) in MS...

PURPOSE: Screening for paraneoplastic antibodies is often performed by means of indirect immunofluorescence on primate cerebellar slices. However, atypical immunofluorescence patterns, i.e. patterns that are not specifically related to paraneoplastic antibodies, are often reported. The clinical significance of these patterns is not clear. Therefore, the purpose of this study was to determine the significance and diagnostic value-in terms of a paraneoplastic neurological syndrome or other neurological disease being diagnosed in the patient-of such atypical immunofluorescence screening patterns on primate cerebellum...

PURPOSE: Although many assays have been developed to detect anti-aquaporin-4 (AQP4) antibodies, most of these assays require sophisticated techniques and are thus only available at specialized laboratories. The aim of this study was to evaluate the analytical and clinical performance of a new commercial enzyme-linked immunosorbent assay (ELISA RSR, AQP4 Ab Version 2) to detect anti-AQP4 antibodies performed on a fully automated system (SkyLAB 752). METHODS: Serum samples from 64 patients with neuromyelitis optica spectrum disorders (NMOSD) (including NMO, longitudinally extensive myelitis-LETM, optical neuritis and myelitis) and 27 controls were tested for anti-AQP4 antibodies...

Background: Apart from endoscopic interventions, readily attainable cost-effective biomarkers for ulcerative colitis (UC) assessment are required. For this purpose, we evaluated differential leucocytic ratio, mainly neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) as simple available indicators of disease activity in patients with ulcerative colitis. Methods: Study conducted on 80 UC patients who were classified into two groups of 40 each according to Mayo score and colonoscopic findings...

Purpose: The introduction of the anti-phosphatidylserine/prothrombin (aPS/PT) antibodies among the routinely investigated anti-phospholipid (aPL) antibodies led to an improvement in anti-phospholipid syndrome (APS) laboratory diagnostic performance; however, their pathogenic mechanism is still substantially undefined. To support clinical data and future inclusion as possible new criteria antibodies, we designed a head-to-head study to directly compare the procoagulant effects sustained in vitro by aPS/PT to those sustained by anti-β2-glycoprotein I (aβ2GpI) domain 1-specific antibodies...

BACKGROUND: To calculate the genetic impact of the "HLA-B27" allele on the risk of Behcet's disease (BD) progression using a systematic review and meta-analysis on case control papers. METHODS: A systematic review search was conducted on the MeSH keywords of Behcet's disease, HLAB27 and B27 in PubMed, Scopus, ProQuest, EMBASE, SID, Magiran, IranDoc and IranMedex databases from 1975 to Aug 2017. Data underwent meta-analysis (random effect model) in CMA2 software...

PURPOSE: Inflammatory bowel disease (IBD) primarily includes ulcerative colitis (UC) and Crohn's disease (CD). Thymic stromal lymphopoietin (TSLP) is a cytokine produced by intestinal epithelial cells (IECs) with immunomodulatory properties that plays an important role in the development of regulatory T cell (Treg) responses and tolerance in the gut. On the other hand, IL-33 has been considered as a cytokine with two different properties, inflammatory and anti-inflammatory functions, the latter may play a protective role against chronic intestinal inflammation...