多发性骨髓瘤患者NK细胞杀伤功能异常的研究

OBJECTIVE: To explore the mechanism of NK cell dysfunction in patients with multiple myeloma (MM). METHODS: The expression of inhibitory receptors (CD158a and CD158b) and activating receptors NKG2D and NCRs (NKp30, NKp44 and NKp46) on CD3 (−)CD56(+) NK cell of 13 MM patients and 30 healthy controls were analyzed by flow cytometry. The concentration of soluble NKG2D ligands (MICA, MICB, ULBP1, ULBP2 and ULBP3) in serum was detected by enzyme-linked immunosorbent assay (ELISA), and the cytotoxicity of NK cell against MM cell line by flow cytometry. RESULTS: There are no significant differences of percentage and absolute number of NK cells, and the expression level of CD158a and CD158b between MM patients and healthy individuals (P>0.05). No NKp44 expression was detected on fresh isolated NK cells from both groups. There is no difference in inhibitor receptors expression between MM patients and healthy individuals but the expression of NKG2D, NKp30 and NKp46 on NK cells were higher in MM patients as compared with that in healthy individuals. The concentration of soluble NKG2D ligands in serum was higher in MM patients as compared with that in healthy individuals (P<0.05). Cultured healthy individual's NK cells with MM patient's serum could significantly decrease its cytotoxicity against MM cell line U266 cells [(38.5±6.5)% vs (25.4±5.9)%, P= 0.044]. CONCLUSION: The higher level of soluble NKG2D ligands in serum may be the mechanism of NK cell dysfunction in MM patient.