Immune activation profiles may hint at insulin resistance, MetS

A specific profile of immune activation (IA)—characterized by CD4+ T cell senescence, inflammation, and endothelial, monocyte, and B cell activation—seems to be linked to insulin resistance (IR) and metabolic syndrome (MetS), a recent study has found.

A total of 150 volunteers (mean age 61.7±4.3 years, 76 men) participated in the study; pregnant or breastfeeding women and those on immunomodulatory treatment as well as with related comorbidities were excluded. Using flow cytometry and enzyme-linked immunosorbent assays, the researchers measured 43 different markers of IA from fasting blood samples.

Five distinct IA profiles emerged. Profile 1 was characterized by an abundance of naïve T cells; profiles 2 and 3 showed elevated levels of terminally differentiated and senescent CD4+ and CD8+ T cells, respectively. Profile 4, on the other hand, was dominated by activated natural killer cells, and profile 5 was enriched with monocytes.

Of all the IA profiles, the second showed correlations with both IR and MetS. For instance, individuals with such an IA profile had higher insulinaemia (13.3±9.2 vs 9.7±5.6 µU/mL; p=0.016) and homeostatic model assessment (3.9±3.4 vs 2.4±1.6; p=0.014).

Similarly, waist/hip circumference (0.93±0.09 vs 0.87±0.10; p=0.005) and triglyceridaemia (1.5±1.0 vs 1.1±0.6 mM; p=0.041) were significantly elevated in profile 2 participants. In turn, these individuals were more frequently given antihyperlipidaemic drugs than the other volunteers (p=0.038).

Further characterization of the profile 2 IA showed that aside from an abundance of terminally differentiated and senescent CD4+ T cells, levels of effector memory and exhausted CD4+ T cells were also significantly elevated in this group. Other elevated markers included the tissue plasminogen activator, immunoglobulin A, and soluble CD163, among others.

“Our findings open the way to the identification of markers predictive for MetS and the morbidities it drives, and of new causative factors,” the researchers said.