Grom Alexei A, Villanueva Joyce, Lee Susan, Goldmuntz Ellen A, Passo Murray H, Filipovich Alexandra
William S. Rowe Division of Rheumatology, and the Division of Hematology/Oncology, Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
J Pediatr. 2003 Mar;142(3):292-6. doi: 10.1067/mpd.2003.110.
To assess natural killer (NK) and cytotoxic functions in patients with systemic-onset juvenile rheumatoid arthrithis (soJRA) complicated by macrophage activation syndrome (MAS).
NK cells (CD56+/TCRalphabeta-), NK T cells (CD56+/TCRalphabeta+) and CD8+ cells were assessed for perforin expression by flow cytometry. NK cytotoxic activity was measured after coincubation of mononuclear cells with an NK-sensitive K562 cell line.
Two major patterns of immunologic abnormalities were detected. Four of 7 patients had decreased NK activity, low NK cell numbers, and mildly increased levels of perforin expression in CD8+ and CD56+ cytotoxic cells. Three remaining patients with MAS, however, had decreased NK activity associated with low levels of perforin expression in all cytotoxic cell populations, a pattern indistinguishable from that in carriers of perforin-deficient familial hemophagocytic lymphohistiocytosis. Remarkably, two of these patients had previous episodes of MAS.
NK dysfunction is an immunologic abnormality common to both familial hemophagocytic lymphohistiocytosis and MAS of soJRA. The extent of NK cell abnormalities in soJRA needs to be further investigated.
评估合并巨噬细胞活化综合征(MAS)的全身型幼年类风湿关节炎(soJRA)患者的自然杀伤(NK)细胞及细胞毒性功能。
采用流式细胞术评估NK细胞(CD56+/TCRαβ-)、NK T细胞(CD56+/TCRαβ+)和CD8+细胞中的穿孔素表达。将单核细胞与NK敏感的K562细胞系共孵育后,测量NK细胞的细胞毒性活性。
检测到两种主要的免疫异常模式。7例患者中有4例NK活性降低、NK细胞数量减少,且CD8+和CD56+细胞毒性细胞中的穿孔素表达水平轻度升高。然而,其余3例患有MAS的患者,其NK活性降低,且所有细胞毒性细胞群体中的穿孔素表达水平均较低,这种模式与穿孔素缺陷型家族性噬血细胞性淋巴组织细胞增生症携带者的模式无法区分。值得注意的是,其中2例患者曾有过MAS发作。
NK功能障碍是家族性噬血细胞性淋巴组织细胞增生症和soJRA的MAS共有的免疫异常。soJRA中NK细胞异常的程度有待进一步研究。