PMID- 22339947
OWN - NLM
STAT- MEDLINE
DCOM- 20121217
LR  - 20211021
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 14
IP  - 1
DP  - 2012 Feb 17
TI  - Anti-citrullinated fibronectin antibodies in rheumatoid arthritis are associated 
      with human leukocyte antigen-DRB1 shared epitope alleles.
PG  - R35
LID - 10.1186/ar3744 [doi]
AB  - INTRODUCTION: Fibronectin is one of the most abundant proteins present in the 
      inflamed joint. Here, we characterized the citrullination of fibronectin in the 
      joints of rheumatoid arthritis (RA) patients and studied the prevalence, epitope 
      specificity and human leukocyte antigen (HLA) association of autoantibodies 
      against citrullinated fibronectin in RA. METHODS: Citrullinated residues in 
      fibronectin isolated from RA patient synovial fluid were identified by mass 
      spectrometry. The corresponding citrullinated and non-citrullinated peptides were 
      synthesized and used to analyze the presence of autoantibodies to these peptides 
      in RA sera and sera from other diseases and healthy controls by ELISA. The data 
      were compared with risk factors like shared epitope HLA alleles and smoking, and 
      with clinical features. RESULTS: Five citrullinated residues were identified in 
      fibronectin from RA synovial fluid. RA sera reacted in a citrulline-dependent 
      manner with two out of four citrullinated fibronectin peptides, one of which 
      contains two adjacent citrulline residues, in contrast to non-RA sera, which were 
      not reactive. The most frequently recognized peptide (FN-Cit1035,1036, 
      LTVGLTXXGQPRQY, in which x represents citrulline) was primarily targeted by 
      anti-CCP (cyclic citrullinated peptide) 2-positive RA patients. 
      Anti-FN-Cit1035,1036 autoantibodies were detected in 50% of established 
      anti-CCP2-positive RA patients and in 45% of such patients from a early arthritis 
      clinic. These antibodies appeared to be predominantly of the immunoglobulin G 
      (IgG) isotype and to be associated with HLA shared epitope alleles (odds ratio = 
      2.11). CONCLUSIONS: Fibronectin in the inflamed synovia of RA patients can be 
      citrullinated at least at five positions. Together with the flanking amino acids, 
      three of these citrullinated residues comprise two epitopes recognized by RA 
      autoantibodies. Anti-citrullinated fibronectin peptide antibodies are associated 
      with HLA shared epitope alleles.
FAU - van Beers, Joyce J B C
AU  - van Beers JJ
AD  - Department of Biomolecular Chemistry, Institute for Molecules and Materials, 
      Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, P,O, 
      Box 9101, 6500 HB Nijmegen, The Netherlands. J.vanbeers@ncmls.ru.nl
FAU - Willemze, Annemiek
AU  - Willemze A
FAU - Stammen-Vogelzangs, Judith
AU  - Stammen-Vogelzangs J
FAU - Drijfhout, Jan W
AU  - Drijfhout JW
FAU - Toes, Rene E M
AU  - Toes RE
FAU - Pruijn, Ger J M
AU  - Pruijn GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120217
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Autoantibodies)
RN  - 0 (Epitopes)
RN  - 0 (Fibronectins)
RN  - 0 (HLA-DRB1 Chains)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptides)
RN  - 29VT07BGDA (Citrulline)
SB  - IM
MH  - Alleles
MH  - Amino Acid Sequence
MH  - Analysis of Variance
MH  - Arthritis, Rheumatoid/blood/genetics/*immunology
MH  - Autoantibodies/blood/*immunology
MH  - Binding Sites/genetics
MH  - Citrulline/*immunology/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Epitopes/genetics/*immunology
MH  - Fibronectins/genetics/*immunology/metabolism
MH  - HLA-DRB1 Chains/genetics/*immunology
MH  - Humans
MH  - Immunoglobulin G/blood/immunology
MH  - Logistic Models
MH  - Molecular Sequence Data
MH  - Peptides/genetics/immunology/metabolism
MH  - Smoking/immunology
MH  - Synovial Fluid/immunology/metabolism
MH  - Tandem Mass Spectrometry
PMC - PMC3392834
EDAT- 2012/02/22 06:00
MHDA- 2012/12/18 06:00
PMCR- 2012/02/17
CRDT- 2012/02/21 06:00
PHST- 2011/08/24 00:00 [received]
PHST- 2012/01/05 00:00 [revised]
PHST- 2012/02/17 00:00 [accepted]
PHST- 2012/02/21 06:00 [entrez]
PHST- 2012/02/22 06:00 [pubmed]
PHST- 2012/12/18 06:00 [medline]
PHST- 2012/02/17 00:00 [pmc-release]
AID - ar3744 [pii]
AID - 10.1186/ar3744 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2012 Feb 17;14(1):R35. doi: 10.1186/ar3744.