CD247, a Novel T Cell–Derived Diagnostic and Prognostic Biomarker for Detecting Disease Progression and Severity in Patients With Type 2 Diabetes

Abstract

OBJECTIVEWe have previously shown that chronic inflammation results in immunosuppression associated with CD247 downregulation in T lymphocytes. Type 2 diabetes mellitus (T2DM) is known to be associated with chronic inflammation. We therefore sought to examine CD247 expression levels in patients with T2DM and to assess whether it can serve as a diagnostic and prognostic biomarker for disease complications and outcomes. RESEARCH DESIGN AND METHODSPeripheral blood samples from 75 T2DM patients and 40 healthy control subjects were collected and analyzed for the expression level of CD247 in T lymphocytes. Subjects with T2DM underwent a medical interview with physical examination and were followed for an additional average of 19.2 6 0.9 months to determine the occurrence of major adverse disease end points. The relationship between the level of CD247 expression and disease status at the time of blood draw and the ability of the marker to identify future complications was evaluated. RESULTSWe observed a significant reduction in CD247 expression levels in T lymphocytes of T2DM patients when compared with healthy volunteers. CD247 downregulation was associated with disease severity, complications, and the occurrence of future cardiovascular events, suggesting its potential use not only as a diagnostic but also as a prognostic biomarker. CONCLUSIONSOur results suggest the use of CD247 as a biomarker in diabetic patients for evaluating the state of chronic inflammation that contributes to morbidity and mortality in this disease and for the prediction of future cardiovascular events.Type 2 diabetes mellitus (T2DM) is associated with low-grade chronic inflammation, which may contribute to the development of diabetes-related complications (1). Several nonspecific biomarkers of inflammation, such as hs-CRP, TNF-a, lipoprotein (a), and sICAM-1, have been implicated in disease progression and activity and found to be significantly elevated in diabetic patients with existing coronary artery

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“…CD247 (T-cell surface glycoprotein CD3 zeta chain) plays an important role in antigen recognition in the immune response and shows altered expression patterns in peripheral blood in individuals with Type 2 Diabetes (44). XYLT1 (Xylosyltransferase 1) is necessary for biosynthesis of glycosaminoglycan chains.…”

Whole‐exome sequencing identified mutational profile of a case with T‐cell chronic lymphocytic leukemia

“…It is plausible that cyclosporine effectively inhibited T cells activated via TCR signaling. 6 Nonsynonymous SNVs in DDX3X and TYK2 may also be important because their dysregulation has been implicated in tumorigenesis. 7 We propose that the classification of indolent MTCL must not be based purely on morphological criteria, but should be substantiated by underlying molecular/genetic features as well as clinical manifestations.…”

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“…CD247 (also known as CD3z) is a part of the TCR complex, which plays a key role in receptor expression and signaling associated to T-cell functions (29,30). Eldor et al (31) reported that CD247 downregulation is associated with immunosuppression in T-cells and was correlated with disease progression and severity in patients with type 2 diabetes. Zap70 was enriched in the TCR signaling pathway.…”