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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Clin+Exp+Immunol
2015 ; 182
(2
): 119-31
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Comparative analysis of autoantibodies targeting peptidylarginine deiminase type
4, mutated citrullinated vimentin and cyclic citrullinated peptides in rheumatoid
arthritis: associations with cytokine profiles, clinical and genetic features
#MMPMID26149185
Reyes-Castillo Z
; Palafox-Sánchez CA
; Parra-Rojas I
; Martínez-Bonilla GE
; del Toro-Arreola S
; Ramírez-Dueñas MG
; Ocampo-Bermudes G
; Muñoz-Valle JF
Clin Exp Immunol
2015[Nov]; 182
(2
): 119-31
PMID26149185
show ga
Antibodies against cyclic citrullinated peptides (anti-CCP) are widely used for
diagnosis of rheumatoid arthritis (RA). We performed a comparative analysis of
antibodies targeting the citrullinating enzyme peptidylarginine deiminase type 4
(anti-PAD4) and mutated citrullinated vimentin (anti-MCV) with anti-CCP
autoantibodies in RA patients and examined their relationships with clinical
parameters, cytokine profiles and the PADI4 gene. Autoantibodies were examined by
enzyme-linked immunosorbent assay (ELISA) in sera of 170 RA patients and 103
controls. Cytokine profiles were measured using a multiplex system. PADI4
polymorphisms (89 G > A, 90 T > C and 92 G > C) were genotyped by polymerase
chain reaction-restriction fragment length polymorphism (PCR-RFLP). Anti-PAD4,
anti-MCV and anti-CCP autoantibodies were detected in 24, 61 and 74% of RA
patients, respectively. Positive correlations were observed between anti-PAD4 and
disease duration; anti-CCP and erythrocyte sedimentation rate (ESR); anti-MCV and
ESR and C-reactive protein. Anti-MCV antibodies were associated with high disease
activity score 28 (DAS-28) in early RA. Concentrations of T helper type 1 (Th1)
[tumour necrosis factor (TNF)-?, interleukin (IL)-12, IL-2, IL-1?], Th2 (IL-4,
IL-6, IL-10, IL-13) and Th17 (IL-17) cytokines were higher in RA than in
controls. Th2 and, to a lesser extent, Th1-related cytokines, showed positive
correlations with anti-MCV and anti-CCP. The GTG haplotype in PADI4 was
associated with anti-CCP and anti-MCV, but not anti-PAD4 antibodies. In
conclusion, anti-PAD4 antibodies are detected mainly in established RA, which is
in contrast to the early detection of antibodies against citrullinated
peptide/proteins (ACPAs). Among autoantibodies, anti-MCV appear to perform better
as markers of disease activity. Furthermore, anti-CCP and anti-MCV are associated
genetically with the citrullinating enzyme PAD4 and are related strongly to Th1
and Th2 cytokines, suggesting a feed-forward loop between cytokines and ACPA
production.