Skewed expression of natural-killer (NK)-associated antigens on lymphoproliferations of large granular lymphocytes (LGL).

Killer-immunoglobulin-like receptors (KIR) or C-type lectin-like receptors are heterogeneously expressed on NK cells and small subsets of T cells and might provide a new diagnostic tool for LGL lymphoproliferations (LGLL). We investigated the diagnostic impact of these cell surface molecules in T- and NK-type LGLL. Using three-color flow cytometry we examined the expression patterns of KIR (CD158a/b/e/i), CD85j, lectin-like receptors (CD94, CD161, NKG2A/D) and natural cytotoxicity receptors (NKp30/44/46) in 13 patients with LGLL (10 T-, 3 NK-LGLL) and compared them to those of the corresponding lymphocyte subsets in 20 control subjects. The presence of clonal TCR-gamma rearrangements and of Epstein Barr virus- (EBV) DNA were evaluated by PCR. All patients exhibited an altered expression of NK-associated markers. KIR were either lacking (6/13) or overexpressed (7/13). CD94 expression was significantly higher in all LGLL. NKG2A expression was significantly higher in NK-LGLL. Absence or overexpression was observed for NKG2A in T-LGLL and CD161 in most T/NK-LGLL. In NK-LGLL expression of NKp30 and NKp46 was significantly decreased, whereas CD85j was overexpressed. We consistently found a skewed expression pattern of novel NK markers as a pathological feature of LGLL. These antigens should be included in the diagnostic workup of this rare disease.