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.

Tipo de publicaciónJournal Article
Año de publicación2015
AutoresReyes-Castillo, Z, Palafox-Sánchez, CA, Parra-Rojas, I, Martínez-Bonilla, GE, del Toro-Arreola, S, Ramírez-Dueñas, MG, Ocampo-Bermudes, G, Muñoz-Valle, JF
JournalClin Exp Immunol
Fecha de publicación2015 Nov
Palabras claveAdult, Arthritis, Rheumatoid, Autoantibodies, Blood Sedimentation, Citrulline, Cytokines, Enzyme-Linked Immunosorbent Assay, Female, Gene Frequency, Genotype, Humans, Hydrolases, Male, Middle Aged, Mutant Proteins, Peptides, Cyclic, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Polymorphism, Single Nucleotide, Severity of Illness Index, Th1 Cells, Th17 Cells, Th2 Cells, Vimentin

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)-α, interleukin (IL)-12, IL-2, IL-1β], 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.

Alternate JournalClin. Exp. Immunol.
ID de PubMed26149185
PubMed Central IDPMC4608501