The diagnostic role of autoantibodies in the prediction of organ-specific autoimmune diseases

Abstract Due to their pathogenetic role, many serum auto-antibodies can be detected a long time before the clinical onset and during the course of organ-specific autoimmune diseases. For these reasons, autoantibodies can be used as predictive markers of an ongoing disease (in healthy subjects) and of disease activity and severity (in ill patients). The new multiplex diagnostic technologies introduced recently in laboratory medicine allow the simultaneous detection of several different autoantibodies and can be used for screening purposes in open populations or high-risk groups. This review examines the various autoantibodies of demonstrated predictive role in organ-specific autoimmune diseases and it introduces the state-of-the-art in the detection of multiple autoantibodies with proteomic systems. Clin Chem Lab Med 2008;46:577–87.

[1]  P. Elliott,et al.  Prospective Familial Assessment in Dilated Cardiomyopathy: Cardiac Autoantibodies Predict Disease Development in Asymptomatic Relatives , 2006, Circulation.

[2]  A. Bellastella,et al.  Remission of subclinical adrenocortical failure in subjects with adrenal autoantibodies. , 1993, The Journal of clinical endocrinology and metabolism.

[3]  M. Rewers,et al.  DRB1104 and DQ Alleles: Expression of 21-Hydroxylase Autoantibodies and Risk of Progression to Addison’s Disease1 , 1999 .

[4]  M. Castellano,et al.  Prognostic value of thyrotropin receptor antibodies (TRAb) in Graves' disease: a 120 months prospective study. , 2007, Endocrine journal.

[5]  M. Fu,et al.  Effects of autoantibodies removed by immunoadsorption from patients with dilated cardiomyopathy on neonatal rat cardiomyocytes , 2006, European journal of heart failure.

[6]  F. Seibold,et al.  Neutrophil autoantibodies: a genetic marker in primary sclerosing cholangitis and ulcerative colitis. , 1994, Gastroenterology.

[7]  Martin J. Lohse,et al.  Direct evidence for a β1-adrenergic receptor–directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy , 2004 .

[8]  M. Bennett,et al.  Positive antimitochondrial antibody but normal alkaline phosphatase: Is this primary biliary cirrhosis? , 1986, Hepatology.

[9]  M. Boscaro,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1997 by The Endocrine Society I. Adrenal Cortex and Steroid 21-Hydroxylase Autoantibodies in Adult Patients with Organ-Specific Autoimmune Diseases: Markers of Low Progression , 2022 .

[10]  R. Uibo,et al.  The follow-up of asymptomatic persons with antibodies to pyruvate dehydrogenase in adult population samples , 2001, Journal of Gastroenterology.

[11]  W. Mckenna,et al.  Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy. , 1992, Circulation.

[12]  C. Carella,et al.  Serum thyrotropin receptor antibodies concentrations in patients with Graves' disease before, at the end of methimazole treatment, and after drug withdrawal: evidence that the activity of thyrotropin receptor antibody and/or thyroid response modify during the observation period. , 2006, Thyroid : official journal of the American Thyroid Association.

[13]  A. Miettinen,et al.  Adrenal and steroidal cell antibodies in patients with autoimmune polyglandular disease type I and risk of adrenocortical and ovarian failure. , 1987, The Journal of clinical endocrinology and metabolism.

[14]  B. Rapoport,et al.  Thyroid peroxidase as an autoantigen. , 2007, Thyroid : official journal of the American Thyroid Association.

[15]  J. French,et al.  The incidence of thyroid disorders in the community: a twenty‐year follow‐up of the Whickham Survey , 1995, Clinical endocrinology.

[16]  M. Fu Autoimmunity and idiopathic dilated cardiomyopathy: Where we stand? , 2008, Autoimmunity.

[17]  M. Hertl,et al.  IgG against extracellular subdomains of desmoglein 3 relates to clinical phenotype of pemphigus vulgaris , 2007, Experimental dermatology.

[18]  E. Bonifacio,et al.  Brief Communication: Early Appearance of Islet Autoantibodies Predicts Childhood Type 1 Diabetes in Offspring of Diabetic Parents , 2004, Annals of Internal Medicine.

[19]  A. Chetwynd,et al.  Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort , 2004, Gut.

[20]  N. Powe,et al.  Prevalence of postpartum thyroid dysfunction: a quantitative review. , 2006, Thyroid : official journal of the American Thyroid Association.

[21]  E. Bonifacio,et al.  GAD Autoantibody Affinity and Epitope Specificity Identify Distinct Immunization Profiles in Children at Risk for Type 1 Diabetes , 2007, Diabetes.

[22]  M. Rewers,et al.  A prospective study of the incidence of childhood celiac disease. , 2003, The Journal of pediatrics.

[23]  Nicola Bizzaro,et al.  Are we at a stage to predict autoimmune rheumatic diseases? , 2007, Arthritis and rheumatism.

[24]  Jorma Ilonen,et al.  Prevalence of Celiac disease among children in Finland. , 2003, The New England journal of medicine.

[25]  Jonathan Braun,et al.  Selected loss of tolerance evidenced by Crohn's disease-associated immune responses to auto- and microbial antigens. , 2002, Gastroenterology.

[26]  R. Balicer,et al.  Anti-Saccharomyces cerevisiae and antineutrophil cytoplasmic antibodies as predictors of inflammatory bowel disease , 2005, Gut.

[27]  Y. Shoenfeld,et al.  Prediction and prevention of autoimmune diseases: additional aspects of the mosaic of autoimmunity , 2006, Lupus.

[28]  R. Burlingame,et al.  Multiplex Assays to Diagnose Celiac Disease , 2007, Annals of the New York Academy of Sciences.

[29]  M. Fu,et al.  Antibodies against the beta1-adrenergic receptor induce progressive development of cardiomyopathy. , 2007, Journal of molecular and cellular cardiology.

[30]  Nicola Bizzaro,et al.  NOVEL DIAGNOSTIC METHODS FOR AUTOANTIBODY DETECTION , 2007 .

[31]  N. Bizzaro,et al.  Immunoassay of Anti-Thyroid Autoantibodies: High Analytical Variability in Second Generation Methods , 2002, Clinical chemistry and laboratory medicine.

[32]  R. Wassmuth,et al.  The Karlsburg type 1 diabetes risk study of a normal schoolchild population: association of beta-cell autoantibodies and human leukocyte antigen-DQB1 alleles in antibody-positive individuals. , 2002, The Journal of clinical endocrinology and metabolism.

[33]  J. Ilonen,et al.  Steroid 21-hydroxylase autoantibodies in insulin-dependent diabetes mellitus. Childhood Diabetes in Finland (DiMe) Study Group. , 1997, Clinical immunology and immunopathology.

[34]  M. Knip,et al.  Gestational diabetes identifies women at risk for permanent type 1 and type 2 diabetes in fertile age: predictive role of autoantibodies. , 2006, Diabetes care.

[35]  U. Roggenbuck,et al.  Sensitive thyrotropin and thyrotropin-receptor antibody determinations one month after discontinuation of antithyroid drug treatment as predictors of relapse in Graves' disease. , 2005, Thyroid : official journal of the American Thyroid Association.

[36]  M. Boscaro,et al.  II. Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases: markers of high progression to clinical Addison's disease. , 1997, The Journal of clinical endocrinology and metabolism.

[37]  A. Avramides,et al.  Post-partum thyroiditis in a Mediterranean population: A prospective study of a large cohort of thyroid antibody positive women at the time of delivery , 2002, Journal of endocrinological investigation.

[38]  A. Ziegler,et al.  Predictive value of human leukocyte antigen class II typing for the development of islet autoantibodies and insulin-dependent diabetes postpartum in women with gestational diabetes. , 1999, The Journal of clinical endocrinology and metabolism.

[39]  M. Rewers,et al.  Addison’s Disease* , 2022 .

[40]  M. Scheurlen,et al.  Anti-Saccharomyces cerevisiae Antibodies in Inflammatory Bowel Disease: a Family Study , 2001, Scandinavian journal of gastroenterology.

[41]  W. Wiersinga,et al.  Thyroid peroxidase autoantibodies in euthyroid subjects. , 2005, Best practice & research. Clinical endocrinology & metabolism.

[42]  M. S. Täng,et al.  Importance of Cardiac Reserve for Evaluation and Prediction of Cardiac Function and Morbidity assessed by low-dose dobutamine stress echocardiography , 2007 .

[43]  G. Wallukat,et al.  Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect. , 1994, Circulation.

[44]  Renato Tozzoli,et al.  Recent advances in diagnostic technologies and their impact in autoimmune diseases. , 2007, Autoimmunity reviews.

[45]  E. Bonifacio,et al.  Predictors of postpartum diabetes in women with gestational diabetes mellitus. , 2006, Diabetes.

[46]  J. Ilonen,et al.  Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population. , 2002, The Journal of clinical endocrinology and metabolism.

[47]  Izumi,et al.  Usefulness of the 2 nd Generation Assay for Anti-TSH Receptor Antibodies to Differentiate Relapse of Graves ’ Thyrotoxicosis from Development of Painless Thyroiditis after Antithyroid Drug Treatment for Graves ’ Disease , 2005 .

[48]  C. Coeli,et al.  Value of Combined Clinical Information and Thyroid Peroxidase Antibodies in Pregnancy for the Prediction of Postpartum Thyroid Dysfunction , 2007, American journal of reproductive immunology.

[49]  N. Bizzaro Autoantibodies as predictors of disease: the clinical and experimental evidence. , 2007, Autoimmunity reviews.

[50]  C. Massart,et al.  Clinical value of a new TSH binding inihibitory activity assay using human TSH receptors in the follow‐up of antithyroid drug treated Graves' disease. Comparison with thyroid stimulating antibody bioassay , 2001, Clinical endocrinology.

[51]  W. Wiersinga,et al.  Cell-mediated immunity and postpartum thyroid dysfunction: a possibility for the prediction of disease? , 1998, The Journal of clinical endocrinology and metabolism.

[52]  Roland Jahns,et al.  Direct evidence for a beta 1-adrenergic receptor-directed autoimmune attack as a cause of idiopathic dilated cardiomyopathy. , 2004, The Journal of clinical investigation.

[53]  J. Ilonen,et al.  Beta-cell autoimmunity, genetic susceptibility, and progression to type 1 diabetes in unaffected schoolchildren. , 2001, Diabetes care.

[54]  M. Fu Anti-M2 muscarinic receptor autoantibodies and idiopathic dilated cardiomyopathy. , 1996, International journal of cardiology.

[55]  D. Dazzi,et al.  The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. , 2007, The Journal of clinical endocrinology and metabolism.

[56]  B. Nygaard,et al.  Use of the 2nd generation TRAK human assay did not improve prediction of relapse after antithyroid medical therapy of Graves' disease. , 2002, European journal of endocrinology.

[57]  J. Sanders,et al.  TSH receptor antibodies. , 2007, Thyroid : official journal of the American Thyroid Association.

[58]  M. Rewers,et al.  Prediction of autoantibody positivity and progression to type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). , 2004, The Journal of clinical endocrinology and metabolism.

[59]  C. Canova,et al.  Estimated risk for developing autoimmune Addison's disease in patients with adrenal cortex autoantibodies. , 2006, The Journal of clinical endocrinology and metabolism.

[60]  P. Laurberg,et al.  Postpartum thyroid dysfunction in pregnant thyroid peroxidase antibody-positive women living in an area with mild to moderate iodine deficiency: is iodine supplementation safe? , 2000, The Journal of clinical endocrinology and metabolism.

[61]  A. Ide,et al.  Endocrine and immunogenetic testing in individuals with type 1 diabetes and 21-hydroxylase autoantibodies: Addison's disease in a high-risk population. , 2005, The Journal of clinical endocrinology and metabolism.

[62]  J. Krischer,et al.  Islet cell antibodies predict insulin-dependent diabetes in United States school age children as powerfully as in unaffected relatives. , 1994, The Journal of clinical investigation.

[63]  K. Poppe,et al.  Thyroid autoimmunity and hypothyroidism before and during pregnancy. , 2003, Human reproduction update.

[64]  S. Targan,et al.  Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity. , 1992, Gastroenterology.

[65]  W Harry Hannon,et al.  Serum TSH, T(4), and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). , 2002, The Journal of clinical endocrinology and metabolism.

[66]  K. Van Steen,et al.  New serological markers in inflammatory bowel disease are associated with complicated disease behaviour , 2007, Gut.

[67]  Y. Okamoto,et al.  TSH receptor antibody measurements and prediction of remission in Graves' disease patients treated with minimum maintenance doses of antithyroid drugs. , 2006, Endocrine journal.

[68]  P. Seed,et al.  The severity of cutaneous and oral pemphigus is related to desmoglein 1 and 3 antibody levels , 2001, The British journal of dermatology.

[69]  R Hal Scofield,et al.  Autoantibodies in Rheumatoid Arthritis Autoantibodies in Pregnancy Autoantibodies as Predictors of Disease , 2022 .

[70]  L. Braverman,et al.  Prospective study of the spontaneous course of subclinical hypothyroidism: prognostic value of thyrotropin, thyroid reserve, and thyroid antibodies. , 2002, The Journal of clinical endocrinology and metabolism.

[71]  J. González-Buitrago Multiplexed testing in the autoimmunity laboratory , 2006, Clinical chemistry and laboratory medicine.

[72]  Concepción González,et al.  Clinical evaluation of a microsphere bead-based flow cytometry assay for the simultaneous determination of anti-thyroid peroxidase and anti-thyroglobulin antibodies. , 2005, Clinical biochemistry.

[73]  J. Lazarus,et al.  Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening. , 2004, Thyroid : official journal of the American Thyroid Association.

[74]  Y. Shoenfeld,et al.  Predicting and Preventing Autoimmunity, Myth or Reality? , 2006, Annals of the New York Academy of Sciences.

[75]  O. Goulet,et al.  Anti-Saccharomyces cerevisiae Mannan Antibodies in Familial Crohn's Disease , 1998, American Journal of Gastroenterology.

[76]  J. Węsierska‐Gądek,et al.  Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis , 2006, Hepatology.

[77]  T. Lambert,et al.  Postpartum thyroid dysfunction: clinical assessment and relationship to psychiatric affective morbidity , 1999, Clinical endocrinology.

[78]  Lawrence Steinman,et al.  Proteomics technologies for the study of autoimmune disease. , 2002, Arthritis and rheumatism.

[79]  Second generation assay for thyrotropin receptor antibodies has superior diagnostic sensitivity for Graves' disease. , 1999, The Journal of clinical endocrinology and metabolism.

[80]  D. Weightman,et al.  A new assay for thyrotropin receptor autoantibodies. , 2004, Thyroid : official journal of the American Thyroid Association.

[81]  Stefan Störk,et al.  Stimulating autoantibodies directed against the cardiac beta1-adrenergic receptor predict increased mortality in idiopathic cardiomyopathy. , 2006, American heart journal.

[82]  Elias Zintzaras,et al.  Evaluation of a Microsphere‐Based Flow Cytometric Assay for Diagnosis of Celiac Disease , 2004, Journal of immunoassay & immunochemistry.

[83]  F. Rigon,et al.  COMPLEMENT-FIXING ADRENAL AUTOANTIBODIES AS A MARKER FOR PREDICTING ONSET OF IDIOPATHIC ADDISON'S DISEASE , 1983, The Lancet.

[84]  W. Scherbaum,et al.  Levels of autoantibodies against human TSH receptor predict relapse of hyperthyroidism in Graves' disease. , 2004, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[85]  Z. Halpern,et al.  Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. , 2006, Gastroenterology.

[86]  R. Young,et al.  Can the laboratory affect the investigation and diagnosis of primary biliary cirrhosis? , 2006, Journal of Clinical Pathology.

[87]  C. Scalici,et al.  The natural history of adrenal function in autoimmune patients with adrenal autoantibodies. , 1988, The Journal of endocrinology.

[88]  G. Cooper,et al.  The epidemiology of autoimmune diseases. , 2003, Autoimmunity reviews.

[89]  Noel R Rose,et al.  Epidemiology of autoimmune diseases in Denmark. , 2007, Journal of autoimmunity.

[90]  G. Lichtenstein New serological markers in inflammatory bowel disease are associated with complicated disease behaviour , 2008 .

[91]  M J Fritzler,et al.  Advances and Applications of Multiplexed Diagnostic Technologies in Autoimmune Diseases , 2006, Lupus.

[92]  G. Baumann,et al.  Reduction of morbidity by immunoadsorption therapy in patients with dilated cardiomyopathy. , 2004, International journal of cardiology.

[93]  J. Krischer,et al.  Multiple autoantibodies as predictors of Type 1 diabetes in a general population , 2003, Diabetologia.

[94]  J. Lazarus,et al.  Association of postpartum thyroid dysfunction with antepartum hormonal and immunological changes. , 2003, The Journal of clinical endocrinology and metabolism.

[95]  A. Ziegler,et al.  Prediction of Type 1 Diabetes Postpartum in Patients With Gestational Diabetes Mellitus by Combined Islet Cell Autoantibody Screening: A Prospective Multicenter Study , 1997, Diabetes.

[96]  P. Fernlund,et al.  Islet autoantibodies in the prediction of diabetes in school children. , 2001, Diabetes research and clinical practice.

[97]  A. Notkins New predictors of disease , 2007 .

[98]  P. Bingley,et al.  Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics. , 2004, Diabetes.

[99]  W. Hagopian,et al.  Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies: an 8-year follow-up of the Washington State Diabetes Prediction Study. , 2002, Diabetes care.

[100]  David E. J. Jones,et al.  Natural history of early primary biliary cirrhosis , 1996, The Lancet.

[101]  F. Santeusanio,et al.  Levels of adrenocortical autoantibodies correlate with the degree of adrenal dysfunction in subjects with preclinical Addison's disease. , 1998, The Journal of clinical endocrinology and metabolism.

[102]  Nicola Bizzaro,et al.  Autoantibody profiling of patients with autoimmune thyroid disease using a new multiplexed immunoassay method , 2006, Clinical chemistry and laboratory medicine.

[103]  M. Papp,et al.  Utility of serological markers in inflammatory bowel diseases: gadget or magic? , 2007, World journal of gastroenterology.

[104]  G. Rossi,et al.  Diagnosis and Classification of Diabetes Mellitus The information that follows is based largely on the reports of the Expert Committee on the Diagnosis and Classification of Diabetes (Diabetes Care 20:1183–1197, 1997, and Diabetes Care 26:3160–3167, 2003). , 2008, Diabetes Care.

[105]  P. Bingley,et al.  Combined testing of antibody titer and affinity improves insulin autoantibody measurement: Diabetes Antibody Standardization Program. , 2007, Clinical immunology.