CD26 Expression on T Helper Populations and sCD26 Serum Levels in Patients with Rheumatoid Arthritis

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.

Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis

“…An increase of a Th1 population which expresses high levels of CD26 was also detected in other autoimmune disorders of Th1/Th17 type, for example in patients with multiple sclerosis or Crohn's disease [30,31]. However, the results here support our recent data [16] indicating that those increases are due to the diminution of, at least, a CD4+CD26 subset early on the pathogenic process rather than the enhancement of CD26 high expressing Th1/Th17 subsets. Keeping in mind that the patients we examined had early, untreated RA, our results could suggest that the increase in the percentage of these cells is probably a later event in the immune response in patients with RA.…”

“…It must be noted that our examination did not include the specific subtypes of T lymphocytes. Furthermore, the significantly lower frequency of CD26+ cells in the WBC population of eRA and cRA patients detected in our study could be a consequence of the drop in the percentage of lymphocytes in the total WBC population (also seen as total count in another cohort [16]). This is the first study of CD26 expression on the surface of overall WBCs in eRA patients.…”

“…Examination of CD26 density on lymphocytes and monocytes of patients with cRA showed significantly lower CD26 density compared to eRA patients and healthy individuals. This finding could be partly explained by using DMARD therapy, particularly methotrexate, whose effect on CD26 density on PBMC was already published [16,33].…”

“…However, a growing body of evidence suggests that the pathogenesis of early RA (eRA) includes different cell and cytokine profiles, emphasizing the role of Th17 lymphocytes, Il-17 and Il-23 [13][14][15]. Furthermore, it was shown that different T cell subsets, according to their CD26 expression, are implicated in RA [16]. In this different cell and cytokine milieu, little is known about the possible role of DPPIV/CD26 in the pathogenesis of eRA.…”

CD26 and Asthma: a Comprehensive Review

“…CD26 expression amongst Teff lymphocytes is also variable, and T H17 cells appear to display the highest levels of CD26 according to the following order: T H17 >> T H1 > T H2 [72,[74][75][76][77]. Furthermore, two subsets were reported amongst T H17 cells on the base of CCR4 expression [78], but only the CCR4 − T H17 subset (and not the TGF-β-secreting CCR4 + T H17 subpopulation) has a CD26 high phenotype [79]. This finding likely indicates that the degree of phenotypic diversity found in Teff cells for CD26 levels is also probably present in Tregs and reflects the presence of functionally different subsets that mirror the corresponding Teff subsets [80].…”