The mRNA levels of TGF-β Type II receptor splice variants in monocytes are associated with disease activity in patients with rheumatoid arthritis

Abstract

In rheumatoid arthritis (RA) patients, TGF-β exerts a singular effect on lymphocytes, macrophages, and polymorphonuclear leukocytes. Moreover, evidences indicate that TGF-β1 stimulation affects the expression levels of TGF-β receptors. Therefore, we analysed in different leukocyte subpopulations, whether the mRNA abundance of TGFBR2 splice variants might be related to RA. We isolated different leukocyte subpopulations from peripheral blood from 9 healthy control volunteers and 9 RA patients, matched by gender and age (cohort 1), and 8 additional RA patients (cohort 2). Then we quantified, by RT-qPCR, the mRNA relative abundance of TGFBR2 splice variants (namely TGFBR2A and TGFBR2B) in PMNs, and PBMCs (monocytes and non-monocytes). We first checked whether the TGFBR2-splice variant mRNA profile could be associated with any particular blood cell type both, in healthy control volunteers and in RA patients. In addition, PBMC and PMN mRNA levels were correlated, using Spearman's rank-order correlation test, with clinical and biochemical determinations of RA patients. We have shown that TGFBR2 exhibits an alternative splicing pattern in different subpopulations of human leucocytes from healthy controls, and the lack of it in the same cell type from RA samples. Furthermore, our study yields initial evidence that TGFBR2 mRNA expression levels in monocytes might mirror RA disease activity. mRNA abundance of TGFBR2 splice variants in monocytes shows changes linked to RA disease activity.