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Autoimmunity Reviews Jun 2007Different autoantibodies are often measured simultaneously; this typically occurs when using indirect immunofluorescence on tissue sections or multiplex detection... (Review)
Review
Different autoantibodies are often measured simultaneously; this typically occurs when using indirect immunofluorescence on tissue sections or multiplex detection systems and may generate clinically "unexpected" positivities (i.e., without any relation to the disease under investigation). Their number is expected to increase with the development of microarray systems in autoantibody assays. In general, when examining patients with such unexpected findings, it is necessary to take into account that: a) autoantibody positivities are much more frequent than autoimmune diseases; b) the positive predictive value of an autoantibody positivity depends upon the diagnostic accuracy of the test and disease prevalence; c) autoantibodies may be risk factors for autoimmune disease or may also have a pathogenetic role by themselves. In this article we will highlight the possible problems raised by some relatively common situations, related to anti-nuclear, anti-thyroid, anti-phospholipid and anti-tissue transglutaminase autoantibodies. The need for specific strategies is outlined.
Topics: Antibodies, Antinuclear; Antibodies, Antiphospholipid; Autoantibodies; Autoimmune Diseases; Celiac Disease; Diagnostic Errors; Humans; Immunologic Tests; Protein Array Analysis; Reproducibility of Results; Sensitivity and Specificity; Thyroiditis, Autoimmune
PubMed: 17537379
DOI: 10.1016/j.autrev.2007.01.011 -
Methods in Molecular Biology (Clifton,... 2016Type 1 diabetes (T1D) is a chronic inflammatory disease, caused by the immune mediated destruction of insulin-producing β-cells in the islets of the pancreas (Ziegler...
Type 1 diabetes (T1D) is a chronic inflammatory disease, caused by the immune mediated destruction of insulin-producing β-cells in the islets of the pancreas (Ziegler and Nepom, Immunity 32(4):468-478, 2010). Semiquantitative assays with high specificity and sensitivity for T1D are now available to detect antibodies to the four major islet autoantigens: glutamate decarboxylase (GADA) (Baekkeskov et al., Nature 347(6289):151-156, 1990), the protein tyrosine phosphatase-like proteins IA-2 (IA-2A) and IA-2β (Notkins et al., Diabetes Metab Rev 14(1):85-93, 1998), zinc transporter 8 (ZnT8A) (Wenzlau et al., Proc Natl Acad Sci U S A 104(43):17040-17045, 2007), and insulin (IAA) (Palmer, Diabetes Metab Rev 3(4):1005-1015, 1987). More than 85 % of cases of newly diagnosed or future T1D can be identified by testing for antibodies to GADA and/or IA-2A/IAA, with 98 % specificity (Bingley et al., Diabet Care 24(2):398, 2001). Overall, radioimmunoassay (RIA) is considered the de facto gold standard format for the measurement of T1D autoantibodies (Bottazzo et al., Lancet 2(7892):1279-1283, 1974; Schlosser et al., Diabetologia 53(12):2611-2620, 2010). Here we describe current methods for autoantibody measurement using RIA. These fluid phase assays use radiolabeled ligands and immunoprecipitation to quantify autoantibodies to GAD, IA-2, ZnT8, and insulin (Bonifacio et al., J Clin Endocrinol Metab 95(7):3360-3367, 2010; Long et al., Clin Endocrinol Metab 97(2):632-637, 2012; Williams et al., J Autoimmun 10(5):473-478, 1997).
Topics: Autoantibodies; Autoantigens; Biomarkers; Diabetes Mellitus, Type 1; Humans; Islets of Langerhans; Radioimmunoassay
PubMed: 26659803
DOI: 10.1007/7651_2015_292 -
Reumatismo 2007Apoptosis is the physiologic process that guarantees the cellular exchange; after apoptosis the cellular remains are cleared by phagocytosis. In autoimmunity, some... (Review)
Review
Apoptosis is the physiologic process that guarantees the cellular exchange; after apoptosis the cellular remains are cleared by phagocytosis. In autoimmunity, some mechanisms in apoptosis fail and may result in disease. For instance, a failure in the Fas pathway during lymphoid ontogeny may allow the survival of autoimmune clones; equally the lack of clearance of apoptotic corps containing self-antigens may activate pre-existent auto-reactive clones and may result in autoantibody production. The role of apoptosis in autoimmunity is reviewed.
Topics: Apoptosis; Autoantibodies; Humans
PubMed: 17603689
DOI: 10.4081/reumatismo.2007.87 -
Autoimmunity Reviews Jun 2007Immunology laboratories perform diagnostic tests to identify the autoantibody markers needed to classify disorders which are complex, often rare, and hard to define. The... (Review)
Review
Immunology laboratories perform diagnostic tests to identify the autoantibody markers needed to classify disorders which are complex, often rare, and hard to define. The recent introduction of new markers and the use of increasingly complicated assay procedures can cause difficulty in interpreting test results. Moreover, during the performance of some tests, some autoantibodies which were not requested, and consequently not expected, may be identified by chance. It is advisable for these positive results to be reported only when they have a high predictive value and suggest the possible presence of an autoimmune disease. An interpretative comment on autoantibody test results is crucial in a number of cases: when autoantibodies with a significant clinical correlation (high specificity) are found; when two or more methods are used to determine the same autoantibody and the results disagree; when unexpected autoantibody positivity is found and in case of results generated by further diagnostic tests conducted by the laboratory on its own initiative. The interpretative comment should be based on the patient's personal characteristics (sex, age) and the other laboratory parameters available; it should specify the diagnostic accuracy of the assay methods used, the clinical and diagnostic correlations of the antibodies which tested positive, and any further tests needed to complete the diagnostic process.
Topics: Autoantibodies; Autoimmune Diseases; Diagnostic Errors; Humans; Immunologic Tests; Reproducibility of Results; Sensitivity and Specificity; Statistics as Topic
PubMed: 17537378
DOI: 10.1016/j.autrev.2007.01.007 -
Seminars in Immunology Feb 1996We established an anti-red blood cell (RBC) autoantibody transgenic mouse line, in which almost all B cells were deleted in the periphery. A small number of B-1 cells,... (Review)
Review
We established an anti-red blood cell (RBC) autoantibody transgenic mouse line, in which almost all B cells were deleted in the periphery. A small number of B-1 cells, however, escaped from deletion, survived and expanded in the peritoneal cavity and the gut, because of the absence of RBC. The activation of B-1 cells by enteric bacteria induced autoimmune hemolytic anemia (AIHA). In turn, AIHA was cured by elimination of peritoneal B-1 cells. This Tg mouse line is useful for revealing the generation and activation of B-1 cells, and for clarifying the physiological and pathological roles of B-1 cells.
Topics: Anemia, Hemolytic, Autoimmune; Animals; Autoantibodies; B-Lymphocytes; Disease Models, Animal; Erythrocytes; Humans; Immunity, Mucosal; Intestines; Lymphocyte Activation; Mice; Mice, Transgenic
PubMed: 8850293
DOI: 10.1006/smim.1996.0002 -
Frontiers in Immunology 2019Glaucoma is an optic neurological disorder and the leading cause of irreversible blindness worldwide, with primary open angle glaucoma (POAG) as its most prevalent form....
Glaucoma is an optic neurological disorder and the leading cause of irreversible blindness worldwide, with primary open angle glaucoma (POAG) as its most prevalent form. An early diagnosis of the disease is crucial to prevent loss of vision. Mechanisms behind glaucoma pathogenesis are not completely understood, but disease related alterations in the serological autoantibody profile indicate an immunologic component. These changes in immunoreactivity may serve as potential biomarkers for glaucoma diagnostics. We aimed to identify novel disease related autoantibodies targeting antigens in the trabecular meshwork as biomarkers to support early detection of POAG. We used serological proteome analysis (SERPA) for initial autoantibody profiling in a discovery sample set. The identified autoantibodies were validated by protein microarray analysis in a larger cohort with 60 POAG patients and 45 control subjects. In this study, we discovered CALD1, PGAM1, and VDAC2 as new biomarker candidates. With the use of artificial neural networks, the panel of these candidates and the already known markers HSPD1 and VIM was able to classify subjects into POAG patients and non-glaucomatous controls with a sensitivity of 81% and a specificity of 93%. These results suggest the benefit of these potential autoantibody biomarkers for utilization in glaucoma diagnostics.
Topics: Aged; Autoantibodies; Autoantigens; Biomarkers; Blood Proteins; Chromatography, Liquid; Electrophoresis, Gel, Two-Dimensional; Female; Glaucoma, Open-Angle; Humans; Male; Middle Aged; Protein Array Analysis; Proteome; Proteomics; Severity of Illness Index; Tandem Mass Spectrometry
PubMed: 30899261
DOI: 10.3389/fimmu.2019.00381 -
Pediatric Diabetes May 2011
Topics: Autoantibodies; Child; Diabetes Mellitus, Type 1; Humans; Seroepidemiologic Studies; World Health Organization
PubMed: 21518406
DOI: 10.1111/j.1399-5448.2011.00786.x -
Annals of the Rheumatic Diseases May 2022
Topics: Aged; Aging; Anti-Citrullinated Protein Antibodies; Autoantibodies; Humans; Incidence; Rheumatoid Factor
PubMed: 32471904
DOI: 10.1136/annrheumdis-2020-217609 -
Pediatric Nephrology (Berlin, Germany) Oct 2010DEAP-HUS [Deficiency of CFHR (complement factor H-related) plasma proteins and Autoantibody Positive form of Hemolytic Uremic Syndrome] represents a novel subtype of... (Review)
Review
DEAP-HUS [Deficiency of CFHR (complement factor H-related) plasma proteins and Autoantibody Positive form of Hemolytic Uremic Syndrome] represents a novel subtype of hemolytic uremic syndrome (HUS) with unique characteristics. It affects children and requires special clinical attention in terms of diagnosis and therapy. DEAP-HUS and other atypical forms of HUS share common features, such as microangiopathic hemolytic anemia, acute renal failure, and thrombocytopenia. However, DEAP-HUS has the unique combination of an acquired factor in the form of autoantibodies to the complement inhibitor Factor H and a genetic factor which, in most cases, is the chromosomal deletion of a 84-kbp fragment within human chromosome 1 that results in the absence of the CFHR1 and CFHR3 proteins in plasma. Special attention is required to diagnose and treat DEAP-HUS patients. Most patients show a favorable response to the reduction of autoantibody titers by either plasma therapy, steroid treatment, and/or immunosuppression. In addition, in those DEAP-HUS patients with end-stage renal disease, the reduction of autoantibody titers prior to transplantation is expected to prevent post-transplant disease recurrence by aiming for full complement control at the endothelial cell surface in order to minimize adverse complement and immune reactions.
Topics: Autoantibodies; Autoantigens; Blood Proteins; Child; Complement C3b Inactivator Proteins; Complement Factor H; Hemolytic-Uremic Syndrome; Humans
PubMed: 20157737
DOI: 10.1007/s00467-010-1446-9 -
Journal of Clinical Rheumatology :... Jan 2023The subset of ANA-positive patients with systemic sclerosis (SSc) who lack prototypic SSc-specific autoantibodies (centromere, topoisomerase, RNA polymerase III,...
BACKGROUND/OBJECTIVES:
The subset of ANA-positive patients with systemic sclerosis (SSc) who lack prototypic SSc-specific autoantibodies (centromere, topoisomerase, RNA polymerase III, “triple negative SSc”) is poorly characterized. We assessed clinical features and prevalence of additional autoantibodies in these patients.
METHODS:
In this case series patients with ANA+ and triple negative SSc antibodies were identified from two independent SSc cohorts (n=280) and demographic and clinical data were obtained over two years. Sera were screened for ANA and autoantibodies were examined by immunoblots. Significance was assessed through Fisher’s exact test and Student’s T-test.
RESULTS:
Forty ANA+ triple negative SSc patients (14% of the two SSc cohorts) were identified. Mean age was 53 ± 14.5 years, 53% had limited disease, average disease duration was 9 ± 9.7 years, and MRSS was 7.6 ± 6.8. 47.5% of the patients had digital ulcers, 60% had interstitial lung disease and 15% had pulmonary hypertension. The most common immunofluorescence patterns were speckled and mixed speckled/nucleolar. Of 29 autoantibodies tested, the most prevalent were Ro-52 (50%), Th/To (40%), MDA5 (35%), SAE1 (28%). Ro-52 was associated with ILD (RR 2.67, p<0.001) and elevated CK (RR 2.64, p<0.05), and PM-75 was associated with digital ulcers (RR 2.18, p<0.05).
CONCLUSIONS:
ANA+ triple negative SSc patients represent an understudied and heterogeneous population of patients with a high prevalence of Ro-52 antibodies, an enrichment for myositis specific antibodies, and increased risk of interstitial lung disease. These patients are seen relatively frequently and should be regularly assessed for evidence of myopathy and lung involvement.
Topics: Humans; Autoantibodies; Antibodies, Antinuclear; Scleroderma, Systemic
PubMed: 35767831
DOI: 10.1097/RHU.0000000000001881