title: Skewed expression of natural-killer (NK)-associated antigens on lymphoproliferations of large granular lymphocytes (LGL).
abstract: 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.
authors.affiliation: Department of Hematology, Oncology and Transfusion Medicine, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Germany. lars.fischer@charite.de
authors.forename: Lars
authors.initials: L
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Thomas
authors.initials: T
authors.lastname: Burmeister
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwartz
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000276:immunology*; D004247:DNA / Q000097:blood / Q000302:isolation & purification; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D008232:Lymphoproliferative Disorders / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012016:Reference Values; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D004247:DNA