Liu H, Ozaki K, Matsuzaki Y, Abe M, Kosaka M, Saito S
First Department of Internal Medicine, School of Medicine, University of Tokushima, Japan.
Clin Exp Immunol. 1995 Jun;100(3):480-5. doi: 10.1111/j.1365-2249.1995.tb03726.x.
The inhibiting activity of serum on haematopoiesis has been described in patients with SLE. To explore further the features of serum inhibitor, we first examined the suppression of granulocytic and erythroid colony formation in vitro by serum from patients with SLE using methylcellulose culture. The potent inhibiting activity was demonstrated in six of 20 patients. All of these six patients were associated with leukocytopenia and/or anaemia. Five of 10 sera from patients with active SLE suppressed the colony formation of both burst-forming units of erythrocyte (BFU-E) and colony-forming units of granulocyte/macrophage (CFU-GM), and one serum suppressed BFU-E only. IgG fraction isolated from sera with inhibiting activity suppressed colony formation without complement involvement. The elimination of monocytes and lymphocytes from target mononuclear cells did not affect the suppression by the IgG fractions. The suppressive effect was completely eliminated after incubation of the IgG fractions with progenitor-enriched mononuclear cells. Flow cytometric analysis showed these IgG bound to CD34+ haematopoietic progenitor cells, but not to CD33+ cells. These data suggest that (i) the inhibitor of colony formation in serum was observed in IgG fraction; (ii) its suppressive effect on colony formation was mediated by neither monocytes and lymphocytes nor complements; and (iii) IgG fraction could bind to primitive haematopoietic progenitor cells and suppress the growth of these cells. Thus, IgG autoantibodies to primitive haematopoietic progenitor cells are demonstrated to be present in the sera of a significant proportion of active SLE patients with anaemia and leukocytopenia and to suppress the progenitor cell growth.
系统性红斑狼疮(SLE)患者血清对造血的抑制活性已有相关描述。为进一步探究血清抑制剂的特征,我们首先使用甲基纤维素培养法检测了SLE患者血清在体外对粒细胞和红系集落形成的抑制作用。在20例患者中,有6例表现出较强的抑制活性。这6例患者均伴有白细胞减少和/或贫血。10份活动期SLE患者的血清中,有5份抑制了红细胞爆式集落形成单位(BFU-E)和粒细胞/巨噬细胞集落形成单位(CFU-GM)的集落形成,1份血清仅抑制了BFU-E的集落形成。从具有抑制活性的血清中分离出的IgG组分在无补体参与的情况下抑制了集落形成。从靶单核细胞中去除单核细胞和淋巴细胞并不影响IgG组分的抑制作用。将IgG组分与富含祖细胞的单核细胞孵育后,抑制作用完全消除。流式细胞术分析显示,这些IgG与CD34+造血祖细胞结合,但不与CD33+细胞结合。这些数据表明:(i)血清中集落形成抑制剂存在于IgG组分中;(ii)其对集落形成的抑制作用既不是由单核细胞、淋巴细胞介导的,也不是由补体介导的;(iii)IgG组分可与原始造血祖细胞结合并抑制这些细胞的生长。因此,已证实在相当一部分伴有贫血和白细胞减少的活动期SLE患者血清中存在针对原始造血祖细胞的IgG自身抗体,且该抗体可抑制祖细胞生长。