Utility of HLA-DR in screening panel for inborn errors of immunity

A comprehensive evaluation of immune parameters while screening for inborn errors of immunity (IEIs) provides valuable information about the underlying defect. In 2019, the ICMR-National Institute of Immunohaematology adopted a screening panel modified from the Euroflow consortium-recommended PIDOT tube, the difference being the addition of HLA-DR. In the present study, we evaluate the utility of HLA-DR in our screening panel. The HLA-DR expression on CD3 + T, its CD4+ and CD8+ subsets, natural killer (NK) and double-negative T cells (DNT) was compared between patients and controls. HLA-DR expression on CD3+ T cells or its subsets was significantly elevated in SCID and Omenn's phenotype (P <.001), combined immunodeficiencies (P < .05) including DOCK8 and WAS, diseases of immune dysregulation including FHL (P < .0001) and ALPS (P < .05) and CVID with complications (P < .05). An absence of HLA-DR marker can help in identifying cases of MHC II deficiency at the time of screening including atypical cases which present without reduction in CD4+ T cell counts and reversal of CD4+/CD8+ ratio. ROC analysis revealed a cut-off of 14.62%, 19.11% and 1.5% for percentage HLA-DR expression on CD3+ and CD8+ T cells and HLA-DR on CD8/HLA-DR on CD4, respectively, for FHL. Random forest analysis identified HLA-DR (%) on NK cells, ratio of HLA-DR CD8+/HLA-DR CD4+, NK cell (%), T cell (%), HLA-DR+ CD8(%) and CD45pos NK cell (%) as important predictors for FHL. Evaluation of HLA-DR expression during screening can provide corroborative clues to the diagnosis of underlying IEI along with other immunological abnormalities.