Immune Response, Antibody Titers Seen Prior to Clinical RA

Anti-citrullinated protein antibody epitope spreading begins years prior to RA onset

FRIDAY, Nov. 4 (HealthDay News) -- Anti-citrullinated protein antibody (ACPA) spreading starts several years prior to the onset of clinical rheumatoid arthritis (RA) with a marked increase in ACPA titers seen approximately two to four years before RA diagnosis, according to a study published in the November issue of Arthritis & Rheumatism.

Lotte A. van de Stadt, M.D., from the University of Amsterdam in the Netherlands, and colleagues investigated the mechanism behind ACPA epitope spreading prior to the onset of clinical RA, and assessed the pattern of autoantigen reactivity at the beginning of the immune response. Prior to the onset of clinical RA, a median of six sequential pre-RA serum samples were obtained one to two years apart in 53 patients with RA who tested positive for ACPA. Reactivity to five distinct citrullinated peptides (two peptides derived from fibrinogen, one each from vimentin, alpha enolase, and filaggrin) was measured using an enzyme-linked immunosorbent assay.

The investigators found that seroconversion from ACPA absence to ACPA presence was seen in 25 of the patients. The immune response started with reactivity to one peptide in 72 percent of these patients, without preference for a particular peptide. There was an increase in the number of peptides recognized over time, with no dominant epitope spreading pattern. Low levels of ACPAs were found several years prior to RA diagnosis, while antibody titers showed a marked increase approximately two to four years before RA diagnosis.

"ACPA immune response starts several years prior to the diagnosis of RA in a restricted manner without preference for a specific peptide reactivity," the authors write.

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