title: The fine specificity of IgM anti-citrullinated protein antibodies (ACPA) is different from that of IgG ACPA.
abstract: BACKGROUND
  The antigen recognition pattern of immunoglobulin M (IgM) could, when directed against protein antigens, provide an indication of the antigenic moieties triggering new B cells. The half-life of IgM is short and memory B cells against T-cell-dependent protein antigens typically produce IgG and not IgM antibodies. In this study, we analyzed whether a difference exists between the fine specificity of IgM versus IgG anti-citrullinated protein antibodies (ACPAs).
  
  
  METHODS
  We determined the fine specificity of IgM and IgG ACPAs in 113 ACPA-positive rheumatoid arthritis patients with IgM cyclic citrullinated peptide 2 (CCP2) levels above 100 AU/ml. Fine specificity was assessed by performing ELISA using citrullinated peptides derived from vimentin, fibrinogen-β, fibrinogen-α and α-enolase, as well as citrullinated proteins fibrinogen and myelin basic protein. The arginine counterparts were used as controls.
  
  
  RESULTS
  Recognition of defined citrullinated antigens by IgM ACPA was confined to samples that also displayed recognition by IgG ACPA. However, the IgM ACPA response displayed a more restricted antigen recognition profile than IgG ACPA (OR = 0.26, P < 0.0001).
  
  
  CONCLUSIONS
  Our data show that several defined citrullinated antigens are recognized only by IgG ACPA, whereas others are also recognized by IgM ACPA. These observations suggest that not all citrullinated antigens are able to activate new B cells despite concurrent recognition by IgG ACPA.
authors: Department of Rheumatology, Leiden University Medical Center (LUMC), PO Box 9600, NL-2300 RC Leiden, The Netherlands.
authors: Parawee
authors: P
authors: Suwannalai
authors: Annemiek
authors: A
authors: Willemze
authors: Linda
authors: L
authors: van Toorn
authors: Gerrie
authors: G
authors: Stoeken-Rijsbergen
authors: Nivine
authors: N
authors: Levarht
authors: Jan Wouter
authors: JW
authors: Drijfhout
authors: Tom W J
authors: TW
authors: Huizinga
authors: Rene E M
authors: RE
authors: Toes
authors: Leendert A
authors: LA
authors: Trouw
mesh_terms: D000595:Amino Acid Sequence; D000918:Antibody Specificity / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005340:Fibrinogen / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000276:immunology; D010456:Peptides, Cyclic / Q000276:immunology*; D010751:Phosphopyruvate Hydratase / Q000276:immunology; D055550:Protein Stability; D013997:Time Factors; D014746:Vimentin / Q000276:immunology
chemical_list: D000939:Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D004676:Myelin Basic Protein; D010456:Peptides, Cyclic; D014746:Vimentin; C487763:cyclic citrullinated peptide; D005340:Fibrinogen; D010751:Phosphopyruvate Hydratase