Abstract
We studied dipeptidyl peptidase IV (DPP-IV, CD26) expression in different T helper cells and serum soluble DPP-IV/sCD26 levels in rheumatoid arthritis (RA) patients, correlated these with disease activity score (DAS), and examined how they were affected by different therapies, conventional or biological (anti-TNF, anti-CD20 and anti-IL6R or Ig-CTLA4). The percentage of CD4+CD45R0+CD26- cells was greatly reduced in patients (up to 50%) when compared with healthy subjects. Three other subsets of CD4 cells, including a CD26high Th1-associated population, changed variably with therapies. Data from these subsets (frequency and staining density) significantly correlated with DAS28 or DAS28 components but different in each group of patients undergoing the different therapies. Th17 and Th22 subsets were implicated in RA as independent CCR4+ and CCR4- populations each, with distinct CD26 expression, and were targeted with varying efficiency by each therapy. Serum DPP-IV activity rather than sCD26 levels was lower in RA patients compared to healthy donors. DPP-IV and sCD26 serum levels were found related to specific T cell subsets but not to disease activity. We conclude that, according to their CD26 expression, different cell subsets could serve to monitor RA course, and an uncharacterized T helper CD26- subset, not targeted by therapies, should be monitored for early diagnosis.
Highlights
Molecular biomarkers for earlier diagnosis of rheumatoid arthritis (RA),[1,2], and predictors of response to therapies or follow up markers of disease progression or remission are in demand [3]
While in systemic lupus erythematosus (SLE) patients the number of CD26+ T cells decreases and this reduction positively correlates with sCD26 levels [8], others have reported the opposite behaviour in RA
In order to identify early events that can be targeted with preventive or therapeutic measures; we studied the levels of serum CD26 and DPP-IV activity and its correlation with CD26 cell surface expression in T helper subsets from RA patients, grouped according to the type of therapy: conventional or biological
Summary
Molecular biomarkers for earlier diagnosis of rheumatoid arthritis (RA), (achieving remission of the disease is possible if diagnosed in the early stages)[1,2], and predictors of response to therapies or follow up markers of disease progression or remission are in demand [3]. Low levels of DPP-IV activity or soluble CD26 were observed in immuno-suppressed situations including some tumours; whereas high levels occur in other tumours, and infectious, inflammatory and liver diseases [11] These qualitative or quantitative changes may be important in RA and possibly in the pathogenesis of other diseases, since DPP-IV as a result of its N-terminal X-Pro cleaving activity, regulates chemotactic responses to the inflammatory chemokines CCL, 3–5, 11 and 22, and CXCL, 2 and 9–12 [9], including SDF-1 [12,13]; In addition, it regulates other biologically active peptides such as NPY and VIP, recently implicated in RA [14]. While in SLE patients the number of CD26+ T cells decreases and this reduction positively correlates with sCD26 levels [8], others have reported the opposite behaviour in RA It has been described [15] that patients with active disease display higher percentages of (mainly) CD4+ CD26+ T cells and higher CD26 surface density, whereas CD26 expression on synovial fluid T lymphocytes is low. In order to identify early events that can be targeted with preventive or therapeutic measures; we studied the levels of serum CD26 and DPP-IV activity and its correlation with CD26 cell surface expression in T helper subsets from RA patients, grouped according to the type of therapy: conventional or biological (using immunomodulating agents)
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