Jasin H E, Orozco J H, Ziff M
Department of Internal Medicine, Rheumatic Diseases Unit, University of Texas Southwestern Medical School, Dallas, Texas 75235, USA.
J Clin Invest. 1974 Feb;53(2):343-53. doi: 10.1172/JCI107566.
To study possible mechanisms responsible for the increased susceptibility to infection of patients with active systemic lupus erythematosus (SLE), a study of the serum heat-labile opsonic capacity (HLOC) in such patients was undertaken. With leukocytes from normal donors, the sera of 12 of 30 patients with active SLE demonstrated decreased HLOC for E. coli 075. The phagocytic activity was partially restored by normal serum, suggesting that decreased HLOC was responsible for the defective phagocytosis. While 8 of 10 patients with active SLE and concomitant infections showed deficient opsonic capacity to E. coli 075, only 4 of 20 such patients without infections showed the defect (P = 0.01). None of 12 patients with inactive disease had deficient opsonic capacity. Similar results were obtained with S. aureus 502A as the test bacterium. In the patients surviving infection, recovery of normal serum opsonic capacity was rapid and usually coincided with an increase of serum complement to normal levels. In three patients with active SLE and infection, the causative microorganisms were isolated and opsonic capacity for these organisms tested with the individual patients' sera. In each case, sera obtained at the onset of the infectious episode had low opsonic capacity when compared with normal sera. Serum C3 proactivator levels were low in 9 of 11 sera with deficient opsonic capacity. However, similar low values were found in other SLE sera with normal HLOC, suggesting that other factors of the opsonic system were also depleted. Addition of the classical complement components C1, C4, C2, C3, and C5 to sera with deficient HLOC failed to restore activity. Addition of pure C3 proactivator also failed to restore activity. However, addition of C3 proactivator together with 50 degrees C-heated normal serum restored activity, indicating that factors active at the early steps of opsonic activation via the alternative pathway of complement were necessary to restore opsonic activity. These findings indicate that in active SLE, a decrease of components of the alternate pathway of complement activation results in an acquired defect of serum HLOC and perhaps other related complement-mediated functions. This defect may be an important factor in the increased susceptibility to infections of patients with active systemic lupus erythematosus.
为研究活动期系统性红斑狼疮(SLE)患者感染易感性增加的可能机制,对这类患者的血清热不稳定调理素能力(HLOC)进行了研究。用正常供体的白细胞检测发现,30例活动期SLE患者中有12例血清对大肠杆菌075的HLOC降低。正常血清可部分恢复吞噬活性,提示HLOC降低是吞噬功能缺陷的原因。10例伴有感染的活动期SLE患者中有8例对大肠杆菌075的调理素能力不足,而20例无感染的此类患者中只有4例出现该缺陷(P = 0.01)。12例非活动期疾病患者均无调理素能力不足。以金黄色葡萄球菌502A作为测试细菌也得到了类似结果。在感染存活的患者中,血清正常调理素能力迅速恢复,通常与血清补体增加至正常水平同时发生。在3例活动期SLE合并感染患者中,分离出致病微生物,并用患者个体血清检测对这些微生物的调理素能力。在每种情况下,与正常血清相比,感染发作时获得的血清调理素能力均较低。11例调理素能力不足的血清中有9例血清C3前活化剂水平较低。然而,在其他HLOC正常的SLE血清中也发现了类似的低值,提示调理素系统的其他因素也有消耗。向HLOC不足的血清中添加经典补体成分C1、C4、C2、C3和C5未能恢复活性。添加纯C3前活化剂也未能恢复活性。然而,添加C3前活化剂与50℃加热的正常血清一起可恢复活性,表明通过补体替代途径在调理素激活早期起作用的因子是恢复调理素活性所必需的。这些发现表明,在活动期SLE中,补体激活替代途径成分的减少导致血清HLOC获得性缺陷以及可能的其他相关补体介导功能缺陷。这种缺陷可能是活动期系统性红斑狼疮患者感染易感性增加的一个重要因素。