PMID- 18006540
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20191210
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 67
IP  - 3
DP  - 2008 Mar
TI  - Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and 
      associations with disease severity.
PG  - 414-7
AB  - BACKGROUND: Antibodies targeting citrullinated antigens are specific for 
      rheumatoid arthritis (RA). Citrullination is catalysed by the peptidylarginine 
      deiminase (PAD) enzyme family. Critical enzymes are often targeted by 
      disease-specific antibodies in complex immune-mediated diseases. Here, we have 
      tested for autoantibodies against human recombinant PAD4 (hPAD4) in Caucasian RA 
      patients. METHODS: A time-resolved fluorometric immunoassay based on hPAD4 was 
      developed to analyse sera from two RA cohorts (n = 237 and n = 177), one systemic 
      lupus erythaematosus (SLE) cohort (n = 84) and 148 healthy controls. Simple and 
      multiple analyses were performed to examine possible associations between 
      anti-hPAD4 and disease variables. RESULTS: Raised levels of anti-hPAD4 IgG were 
      found in both RA cohorts compared to the controls, and 23% of the RA patients 
      were anti-hPAD4 IgG positive. Anti-hPAD4 was associated with anti-cyclic 
      citrullinated peptide (CCP) and rheumatoid factor (RF), as well as increased 
      physical disability. Anti-hPAD4 was also associated with higher longitudinal 
      radiographic damage scores and increased clinical joint pathology, but weaker 
      than anti-CCP. No associations were found between anti-hPAD4 and selected Human 
      leukocyte antigen (HLA)-DRB1 variants. CONCLUSIONS: Approximately 23% of 
      Caucasian RA patients have serum IgG antibodies against hPAD4. The presence of 
      serum anti-hPAD4 IgG was in simple analyses associated with a more severe disease 
      phenotype, and the association with physical disability was maintained in 
      multiple analyses.
FAU - Halvorsen, E H
AU  - Halvorsen EH
AD  - Institute of Immunology, University of Oslo, Rikshospitalet University Hospital, 
      0027 Oslo, Norway. eirikhha@medisin.uio.no
FAU - Pollmann, S
AU  - Pollmann S
FAU - Gilboe, I-M
AU  - Gilboe IM
FAU - van der Heijde, D
AU  - van der Heijde D
FAU - Landewe, R
AU  - Landewe R
FAU - Odegard, S
AU  - Odegard S
FAU - Kvien, T K
AU  - Kvien TK
FAU - Molberg, O
AU  - Molberg O
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071115
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Autoantibodies)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Recombinant Proteins)
RN  - 0 (cyclic citrullinated peptide)
RN  - 9009-79-4 (Rheumatoid Factor)
RN  - EC 3.- (Hydrolases)
RN  - EC 3.5.3.15 (PADI4 protein, human)
RN  - EC 3.5.3.15 (Protein-Arginine Deiminase Type 4)
RN  - EC 3.5.3.15 (Protein-Arginine Deiminases)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Arthritis, Rheumatoid/diagnostic imaging/*immunology/pathology
MH  - Autoantibodies/*blood
MH  - Cohort Studies
MH  - Female
MH  - Fluorometry
MH  - Humans
MH  - Hydrolases/*immunology
MH  - Immunoglobulin G/*blood
MH  - Lupus Erythematosus, Systemic/immunology
MH  - Male
MH  - Middle Aged
MH  - Peptides, Cyclic/immunology
MH  - Protein-Arginine Deiminase Type 4
MH  - Protein-Arginine Deiminases
MH  - Radiography
MH  - Recombinant Proteins/immunology
MH  - Rheumatoid Factor/blood
MH  - Severity of Illness Index
EDAT- 2007/11/17 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/11/17 09:00
PHST- 2007/11/17 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/11/17 09:00 [entrez]
AID - ard.2007.080267 [pii]
AID - 10.1136/ard.2007.080267 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2008 Mar;67(3):414-7. doi: 10.1136/ard.2007.080267. Epub 2007 Nov 
      15.