Epitope specificity and significance in systemic autoimmune diseases

Autoimmune diseases are characterized by self‐reactive immune processes mediated by B and T cells. These disorders exhibit a spectrum of clinical features that range from local or organ specific to systemic diseases. Although a variety of putative mechanisms that trigger the loss of tolerance and thus the genesis of autoimmunity have been identified, for the most part the precise mechanisms remain illusive. Nevertheless, it is widely appreciated that autoantibodies are useful both in the diagnosis of autoimmune disorders and as molecular biological tools to study cellular processes in which the target antigens are involved. Several methods and technologies, including protein fragments, synthetic peptides, phage display, or structural analyses have been developed for the characterization of the specificity of the autoimmune reactions. The present review provides an overview of the autoantibody epitopes in systemic autoimmune diseases as they relate to the clinical relevance and applications of certain autoepitopes and the technologies that are used to classify and identify them.

[1]  M. Fritzler,et al.  Latest update on the Ro/SS-A autoantibody system. , 2009, Autoimmunity reviews.

[2]  M. Fritzler,et al.  The changing landscape of the clinical value of the PM/Scl autoantibody system , 2009, Arthritis research & therapy.

[3]  I. Mackay,et al.  Apotopes and the biliary specificity of primary biliary cirrhosis , 2009, Hepatology.

[4]  J. Harley,et al.  Early targets of nuclear RNP humoral autoimmunity in human systemic lupus erythematosus. , 2009, Arthritis and rheumatism.

[5]  A. Cava Lupus and T Cells , 2009 .

[6]  Ş. Yavuz,et al.  Comparative Performance Analysis of 4 Different Anti-Citrullinated Protein Assays in the Diagnosis of Rheumatoid Arthritis , 2009, The Journal of Rheumatology.

[7]  D. Huscher,et al.  Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients , 2009, Arthritis research & therapy.

[8]  R. Burlingame,et al.  A comparative study of IgG second- and third-generation anti-cyclic citrullinated peptide (CCP) ELISAs and their combination with IgA third-generation CCP ELISA for the diagnosis of rheumatoid arthritis , 2009, Clinical Rheumatology.

[9]  E. Peeva,et al.  B-cell-directed therapies in systemic lupus erythematosus. , 2008, Seminars in arthritis and rheumatism.

[10]  M. Fritzler,et al.  Limited reliability of the indirect immunofluorescence technique for the detection of anti-Rib-P antibodies , 2008, Arthritis research & therapy.

[11]  Michael W. Jackson,et al.  B cell apotopes of the 60-kDa Ro/SSA and La/SSB autoantigens. , 2008, Journal of autoimmunity.

[12]  W. V. van Venrooij,et al.  Anti‐CCP Antibody, a Marker for the Early Detection of Rheumatoid Arthritis , 2008, Annals of the New York Academy of Sciences.

[13]  V. Kraus,et al.  Biomarkers associated with clinical phenotypes of hand osteoarthritis in a large multigenerational family: the CARRIAGE family study. , 2008, Osteoarthritis and cartilage.

[14]  Marvin J Fritzler,et al.  Challenges to the use of autoantibodies as predictors of disease onset, diagnosis and outcomes. , 2008, Autoimmunity reviews.

[15]  R. Cervera,et al.  Anti-chromatin (anti-nucleosome) antibodies: diagnostic and clinical value. , 2008, Autoimmunity reviews.

[16]  Ehud Shapiro,et al.  De novo DNA synthesis using single molecule PCR , 2008, Nucleic acids research.

[17]  R. H. Scofield,et al.  Autoimmunity and oxidatively modified autoantigens. , 2008, Autoimmunity reviews.

[18]  T. Witte IgM Antibodies Against dsDNA in SLE , 2008, Clinical reviews in allergy & immunology.

[19]  G. Steiner,et al.  B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new specific antibody marker for active lupus disease , 2008, Annals of the rheumatic diseases.

[20]  A. Tincani,et al.  Pathogenic anti-nucleosome antibodies , 2008, Lupus.

[21]  R. Haigh,et al.  Consequence of neo-antigenicity of the 'altered self'. , 2008, Rheumatology.

[22]  S. Gabriel,et al.  Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part II. , 2008, Arthritis and rheumatism.

[23]  F. Ohsuzu,et al.  Primary biliary cirrhosis in female subjects with sicca-associated antibodies , 2007, Modern rheumatology.

[24]  S. Svegliati,et al.  Pathogenic autoantibodies in systemic sclerosis. , 2007, Current opinion in immunology.

[25]  M. Fritzler,et al.  Update on autoantibodies in systemic sclerosis , 2007, Current opinion in rheumatology.

[26]  K. Kessenbrock,et al.  Synthetic peptides: the future of patient management in systemic rheumatic diseases? , 2007, Current medicinal chemistry.

[27]  K. Kessenbrock,et al.  Diverse humoral autoimmunity to the ribosomal P proteins in systemic lupus erythematosus and hepatitis C virus infection , 2007, Journal of Molecular Medicine.

[28]  Reinout Raijmakers,et al.  Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. , 2007, Autoimmunity reviews.

[29]  D. Deforce,et al.  Do all anti-citrullinated protein/peptide antibody tests measure the same? Evaluation of discrepancy between anti-citrullinated protein/peptide antibody tests in patients with and without rheumatoid arthritis , 2007, Annals of the rheumatic diseases.

[30]  M. Fritzler,et al.  Effect of dsDNA binding to SmD-derived peptides on clinical accuracy in the diagnosis of systemic lupus erythematosus , 2007, Arthritis research & therapy.

[31]  M. Petri,et al.  Asymmetric dimethylarginine is a marker of poor prognosis and coronary calcium in systemic lupus erythematosus. , 2007, The Journal of rheumatology.

[32]  M. Hudson,et al.  A comparison of the frequency of antibodies to cyclic citrullinated peptides using a third generation anti-CCP assay (CCP3) in systemic sclerosis, primary biliary cirrhosis and rheumatoid arthritis , 2007, Clinical Rheumatology.

[33]  S. Barr,et al.  Autoantibodies in lupus nephritis patients requiring renal transplantation , 2007, Lupus.

[34]  Michael J Taussig,et al.  Crystal structure of a human autoimmune complex between IgM rheumatoid factor RF61 and IgG1 Fc reveals a novel epitope and evidence for affinity maturation. , 2007, Journal of molecular biology.

[35]  J. Buyon,et al.  Different temporal expression of immunodominant Ro60/60 kDa‐SSA and La/SSB apotopes , 2007, Clinical and experimental immunology.

[36]  R. Raijmakers,et al.  Challenges and Controversies in Autoantibodies Associated with Systemic Rheumatic Diseases , 2007 .

[37]  Lila Farrag,et al.  A study of conformational restraints on reactivity of human PR3-specific autoantibodies (ANCA) facilitated through protein folding manipulations of a new recombinant proteinase 3 protein , 2007, Autoimmunity.

[38]  J. Guthridge,et al.  Fine specificity mapping of autoantigens targeted by anti-centromere autoantibodies. , 2006, Journal of autoimmunity.

[39]  M. Gaubitz Epidemiology of connective tissue disorders. , 2006, Rheumatology.

[40]  J. Fisk,et al.  Anti-NR2 glutamate receptor antibodies and cognitive function in systemic lupus erythematosus. , 2006, The Journal of rheumatology.

[41]  G. Riemekasten,et al.  The binding of lupus-derived autoantibodies to the C-terminal peptide (83–119) of the major SmD1 autoantigen can be mediated by double-stranded DNA and nucleosomes , 2006, Annals of the rheumatic diseases.

[42]  C. Chichester,et al.  Review: Collagen markers in early arthritic diseases. , 2006, Clinica chimica acta; international journal of clinical chemistry.

[43]  G. Tsokos In the Beginning Was Sm , 2006, The Journal of Immunology.

[44]  A. Tzioufas,et al.  Autoantibodies to intracellular autoantigens and their B-cell epitopes: Molecular Probes to Study the Autoimmune Response , 2006, Critical reviews in clinical laboratory sciences.

[45]  J. Harley,et al.  Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus , 2006, Autoimmunity.

[46]  K. Kessenbrock,et al.  International Multicenter Evaluation of Autoantibodies to Ribosomal P Proteins , 2006, Clinical and Vaccine Immunology.

[47]  Wei Zhang,et al.  A peptide DNA surrogate that binds and inhibits anti-dsDNA antibodies. , 2005, Clinical immunology.

[48]  H. Bagavant,et al.  Epitope spreading within lupus-associated ribonucleoprotein antigens. , 2005, Clinical immunology.

[49]  G. Pruijn,et al.  Apoptotic modifications affect the autoreactivity of the U1 snRNP autoantigen. , 2005, Autoimmunity reviews.

[50]  H. Doyle,et al.  Posttranslational Modifications of Self‐Antigens , 2005, Annals of the New York Academy of Sciences.

[51]  R. Raijmakers,et al.  Clinical evaluation of autoantibodies to a novel PM/Scl peptide antigen , 2005, Arthritis research & therapy.

[52]  S. Bombardieri,et al.  Anti-Sm and anti-RNP antibodies , 2005, Autoimmunity.

[53]  G. Pruijn,et al.  Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease , 2005, Arthritis research & therapy.

[54]  M. Fritzler,et al.  Improved Serological Differentiation between Systemic Lupus Erythematosus and Mixed Connective Tissue Disease by Use of an SmD3 Peptide-Based Immunoassay , 2005, Clinical Diagnostic Laboratory Immunology.

[55]  M. Fritzler,et al.  Identification of a SmD3 epitope with a single symmetrical dimethylation of an arginine residue as a specific target of a subpopulation of anti-Sm antibodies , 2004, Arthritis research & therapy.

[56]  S. Pestka,et al.  Spliceosome Sm proteins D1, D3, and B/B' are asymmetrically dimethylated at arginine residues in the nucleus. , 2004, Biochemical and biophysical research communications.

[57]  Y. Shoenfeld,et al.  Autoantibody explosion in systemic lupus erythematosus: more than 100 different antibodies found in SLE patients. , 2004, Seminars in arthritis and rheumatism.

[58]  I. Sanz,et al.  B cells as therapeutic targets for rheumatic diseases , 2004, Current opinion in rheumatology.

[59]  E. Chan,et al.  Clinical and serological associations of autoantibodies to GW bodies and a novel cytoplasmic autoantigen GW182 , 2003, Journal of Molecular Medicine.

[60]  J. Koziol,et al.  A critical evaluation of enzyme immunoassay kits for detection of antinuclear autoantibodies of defined specificities. III. Comparative performance characteristics of academic and manufacturers' laboratories. , 2003, The Journal of rheumatology.

[61]  R Hal Scofield,et al.  Development of autoantibodies before the clinical onset of systemic lupus erythematosus. , 2003, The New England journal of medicine.

[62]  M. Mahler,et al.  Advances in B-cell epitope analysis of autoantigens in connective tissue diseases. , 2003, Clinical immunology.

[63]  E. Chan,et al.  A panel of monoclonal antibodies to cytoplasmic GW bodies and the mRNA binding protein GW182. , 2003, Hybridoma and hybridomics.

[64]  R. Williams,et al.  Characterization of the human autoimmune response to the major C-terminal epitope of the ribosomal P proteins , 2003, Journal of Molecular Medicine.

[65]  G. Pruijn,et al.  Human recombinant anti-La (SS-B) autoantibodies demonstrate the accumulation of phosphoserine-366-containing la isoforms in nucleoplasmic speckles. , 2003, European journal of cell biology.

[66]  H. Gausepohl,et al.  Chemistry of Fmoc Peptide Synthesis on Membranes , 2002 .

[67]  Hanspeter Herzel,et al.  Identification of distinct antibody epitopes and mimotopes from a peptide array of 5520 randomly generated sequences. , 2002, Journal of immunological methods.

[68]  N. Ede Multiple parallel synthesis of peptides on SynPhase grafted supports. , 2002, Journal of immunological methods.

[69]  R. Frank The SPOT-synthesis technique. Synthetic peptide arrays on membrane supports--principles and applications. , 2002, Journal of immunological methods.

[70]  M. Mahler,et al.  Development of a CENP-A/CENP-B-specific immune response in a patient with systemic sclerosis. , 2002, Arthritis and rheumatism.

[71]  H. Ménard,et al.  Autoantigenic posttranslational modifications of proteins: does it apply to rheumatoid arthritis? , 2002, Current opinion in rheumatology.

[72]  Philippa Marrack,et al.  Autoimmune disease: why and where it occurs , 2001, Nature Medicine.

[73]  M. Mahler,et al.  A population of autoantibodies against a centromere-associated protein A major epitope motif cross-reacts with related cryptic epitopes on other nuclear autoantigens and on the Epstein-Barr nuclear antigen 1 , 2001, Journal of Molecular Medicine.

[74]  A. Silverstein Autoimmunity versus horror autotoxicus: The struggle for recognition , 2001, Nature Immunology.

[75]  K. Fong,et al.  Peptide mimicking antigenic and immunogenic epitope of double-stranded DNA in systemic lupus erythematosus. , 2001, International immunology.

[76]  M. Hearth-Holmes,et al.  Prevalence of Active Hepatitis C Virus Infection in Patients with Systemic Lupus Erythematosus , 2001, The American journal of the medical sciences.

[77]  M. Mahler,et al.  Fine-specificity of the anti-CENP-A B-cell autoimmune response , 2000, Journal of Molecular Medicine.

[78]  B Westerlund-Wikström,et al.  Peptide display on bacterial flagella: principles and applications. , 2000, International journal of medical microbiology : IJMM.

[79]  R. Lührmann,et al.  The C-terminal RG Dipeptide Repeats of the Spliceosomal Sm Proteins D1 and D3 Contain Symmetrical Dimethylarginines, Which Form a Major B-cell Epitope for Anti-Sm Autoantibodies* , 2000, The Journal of Biological Chemistry.

[80]  G. Pruijn,et al.  Citrullination: a small change for a protein with great consequences for rheumatoid arthritis , 2000, Arthritis research.

[81]  T. Lowe,et al.  Fibrillarin-associated box C/D small nucleolar RNAs in Trypanosoma brucei. Sequence conservation and implications for 2'-O-ribose methylation of rRNA. , 2000, The Journal of biological chemistry.

[82]  M. Mahler,et al.  Identification of an α-helical epitope region on the PM/Scl-100 autoantigen with structural homology to a region on the heterochromatin p25β autoantigen using immobilized overlapping synthetic peptides , 2000, Journal of Molecular Medicine.

[83]  I. Pettersson,et al.  Key residues revealed in a major conformational epitope of the U1-70K protein. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[84]  James,et al.  Shared Early Autoantibody Recognition Events in the Development of Anti‐Sm B/B' in Human Lupus , 1999, Scandinavian journal of immunology.

[85]  J. Schneider-Mergener,et al.  A novel epitope on the C-terminus of SmD1 is recognized by the majority of sera from patients with systemic lupus erythematosus. , 1998, The Journal of clinical investigation.

[86]  J. Harley,et al.  B‐cell epitope spreading in autoimmunity , 1998, Immunological reviews.

[87]  B. Diamond,et al.  Immunization with a Peptide Surrogate for Double-stranded DNA (dsDNA) Induces Autoantibody Production and Renal Immunoglobulin Deposition , 1998, The Journal of experimental medicine.

[88]  Jerrold S. Levine,et al.  Apoptosis and autoimmunity , 1997, Current opinion in nephrology and hypertension.

[89]  E. Tan,et al.  The autoimmunity-inducing xenobiotic mercury interacts with the autoantigen fibrillarin and modifies its molecular and antigenic properties. , 1997, Journal of immunology.

[90]  J. Harley,et al.  Peptide autoantigenicity of the small nuclear ribonucleoprotein C. , 1995, Clinical and experimental rheumatology.

[91]  E. Tan,et al.  Autoantibodies in the diagnosis of systemicrheumatic diseases , 1995 .

[92]  S. Turley,et al.  Analysis of the autoantibody response to fibrillarin in human disease and murine models of autoimmunity. , 1995, Journal of immunology.

[93]  R. Burlingame,et al.  The central role of chromatin in autoimmune responses to histones and DNA in systemic lupus erythematosus. , 1994, The Journal of clinical investigation.

[94]  J. Mott,et al.  Biochemical diversity in a phage display library of random decapeptides. , 1993, Gene.

[95]  M. Fritzler,et al.  Epitope mapping of histone 5 (H5) with systemic lupus erythematosus, procainamide-induced lupus and hydralazine-induced lupus sera. , 1993, Molecular immunology.

[96]  M. Blüthner,et al.  Cloning and characterization of the cDNA coding for a polymyositis- scleroderma overlap syndrome-related nucleolar 100-kD protein , 1992, The Journal of experimental medicine.

[97]  R. Houghten,et al.  Generation and use of synthetic peptide combinatorial libraries for basic research and drug discovery , 1991, Nature.

[98]  G. Blobel,et al.  cDNA cloning and sequencing of human fibrillarin, a conserved nucleolar protein recognized by autoimmune antisera. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[99]  M. Fritzler,et al.  Antibodies from patients with systemic lupus erythematosus and drug-induced lupus bind determinants on histone 5 (H5). , 1990, Molecular immunology.

[100]  M. Jannatipour,et al.  Heterologous expression and epitope mapping of a human small nuclear ribonucleoprotein-associated Sm-B'/B autoantigen. , 1990, Journal of immunology.

[101]  E. Tan,et al.  Anti-fibrillarin autoantibodies in mercury-treated mice. , 1989, Clinical and experimental immunology.

[102]  T. Mimori,et al.  The U2 small nuclear ribonucleoprotein particle as an autoantigen. Analysis with sera from patients with overlap syndromes. , 1988, The Journal of clinical investigation.

[103]  E. Tan Antinuclear antibodies: diagnostic markers and clues to the basis of systemic autoimmunity , 1988, The Pediatric infectious disease journal.

[104]  H. M. Geysen,et al.  Strategies for epitope analysis using peptide synthesis. , 1987, Journal of immunological methods.

[105]  P. Cary,et al.  Antibodies from patients with drug-induced and idiopathic lupus erythematosus react with epitopes restricted to the amino and carboxyl termini of histone. , 1985, Journal of immunology.

[106]  K. Elkon,et al.  Lupus autoantibodies target ribosomal P proteins , 1985, The Journal of experimental medicine.

[107]  G. P. Smith,et al.  Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. , 1985, Science.

[108]  J. Hardin,et al.  The major core histone antigenic determinants in systemic lupus erythematosus are in the trypsin‐sensitive regions , 1984, FEBS letters.

[109]  J F Fries,et al.  The 1982 revised criteria for the classification of systemic lupus erythematosus. , 1982, Arthritis and rheumatism.

[110]  H. Kunkel,et al.  Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. , 1966, Journal of immunology.

[111]  A. La Cava,et al.  Potential for anti-DNA immunoglobulin peptide therapy in systemic lupus erythematosus. , 2009, Expert opinion on biological therapy.

[112]  L. Klareskog,et al.  Antibodies against citrullinated vimentin in rheumatoid arthritis: higher sensitivity and extended prognostic value concerning future radiographic progression as compared with antibodies against cyclic citrullinated peptides. , 2008, Arthritis and rheumatism.

[113]  Atlanta,et al.  Estimates of the prevalence of arthritis and other rheumatic conditions in the United States. Part I. , 2008, Arthritis and rheumatism.

[114]  M. McClain,et al.  An altered immune response to Epstein-Barr nuclear antigen 1 in pediatric systemic lupus erythematosus. , 2006, Arthritis and rheumatism.

[115]  M. McClain,et al.  Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry , 2005, Nature Medicine.

[116]  M. Rowley,et al.  Phage display for epitope determination: a paradigm for identifying receptor-ligand interactions. , 2004, Biotechnology annual review.

[117]  J. Koch,et al.  Affinity Purification and Competition Assays Using Solid-Phase Oligopeptides , 2002 .

[118]  Ronald Frank,et al.  SPOT Synthesis — Scope of Applications , 2002 .

[119]  E. Möncke-Buchner,et al.  Analysis of Protein-DNA Interactions , 2002 .

[120]  C. Schneider,et al.  Identification of major linear epitopes on the sp100 nuclear PBC autoantigen by the gene-fragment phage-display technology. , 1999, Autoimmunity.

[121]  E. Bautz,et al.  Mapping of epitopes recognized by PM/Scl autoantibodies with gene-fragment phage display libraries. , 1996, Journal of immunological methods.

[122]  E. Tan,et al.  Autoantibodies in the diagnosis of systemic rheumatic diseases. , 1995, Seminars in arthritis and rheumatism.

[123]  Kit S. Lam,et al.  A new type of synthetic peptide library for identifying ligand-binding activity , 1992, Nature.

[124]  R. Lührmann,et al.  Mercuric chloride induces autoantibodies against U3 small nuclear ribonucleoprotein in susceptible mice. , 1989, Proceedings of the National Academy of Sciences of the United States of America.