Type 2 Diabetes Reshapes the B-Cell Compartment in Tuberculosis, with Reduction of Transitional B Cells and Expansion of Plasmablasts.
Abstract
Objective
Type 2 diabetes (T2D) increases the risk of tuberculosis (TB) and TB severity; however, its effects on B-cells in the TB-T2D syndemic are not fully understood.
Methods
We evaluated by flow cytometry, the distribution of circulating B-cell subsets in patients with TB disease, TB-T2D, subjects with TB infection (TBI), TBI-T2D, healthy controls (HCs), T2D, patients with pulmonary respiratory diseases other than TB (ORDs), and ORD-T2D. Plasma levels of unspecific or PPD-specific IgG and B-cell-related soluble factors were measured by multiplex assays.
Results
Total B-cell frequency was similar across groups. TB-T2D patients showed decreased transitional B cells compared to TB, TBI-T2D, HC, and T2D. Transitional B-cell frequency significantly and negatively correlated with HbA1c levels in the TB-T2D group. Moreover, plasmablast frequency was increased in TB-T2D compared to TB, TBI-T2D, and T2D. Unspecific or PPD-specific IgG levels were not modulated by T2D. BAFF levels increased in TB and TB-T2D compared to the other groups, whereas the levels of SDF-1 were decreased in TB and TBI irrespective of T2D, compared to the controls.
Conclusions
Overall, T2D reshapes B-cell compartments in TB, reducing potentially anti-inflammatory transitional B-cells and increasing plasmablasts, possibly reinforcing inflammation and impacting B-cell development and humoral immunity in TB-T2D.