NK-cell repertoire is feasible for diagnosing Epstein–Barr virus-infected NK-cell lymphoproliferative disease and evaluating the treatment effect

Epstein-Barr virus (EBV) occasionally infects T and NK cells and causes EBV-infected T/NK-cell lymphoproliferative disease (LPD), which comprises chronic active EBV infection, EBV-associated hemophagocytic syndrome, mosquito allergy, hydroa vacciniforme, aggressive NK-cell leukemia, and NK/T-cell lymphoma. The diagnosis is proven by the monoclonal proliferation of EBV-infected T or NK cells, which is a time-consuming and complicated method. T-cell monoclonality is helpful for the screening of EBV-infected T-cell LPD in patients with EBV-genome burden and is easily shown with T-cell-receptor rearrangement or the T-cell repertoire, whereas NK-cell monoclonality is difficult to prove due to its lacking such rearranged receptors. We investigated a set of killer immunoglobulin-like receptors (KIRs) and also CD94-NKG2 heterodimers on NK cells, namely the NK-cell repertoire. Skewed repertoires were seen in all patients with EBV-infected NK-cell LPD, but not in any patients with EBV-infected T-cell LPD and were restored only after successful treatment. The normal KIR repertoire is variable for each individual and it seems difficult to detect minimal residual EBV-infected lymphocytes. However, the NK-cell repertoire is feasible for identifying EBV-infected NK-cell LPD and evaluating the treatment effect.