Dreskin S C, Goldsmith P K, Gallin J I
J Clin Invest. 1985 Jan;75(1):26-34. doi: 10.1172/JCI111683.
Patients with the hyperimmunoglobulin E and recurrent infection syndrome (HIE) characteristically have frequent skin and respiratory infections caused by Staphylococcus aureus. We have developed a set of enzyme-linked immunosorbent assays that use whole S. aureus (Wood's strain) immobilized on 0.22-micrometers filters and highly specific, affinity-purified enzyme conjugates of goat anti-human IgE, anti-human IgD, anti-human IgG, anti-human IgA, and anti-human IgM. These reagents were used to determine S. aureus-specific immunoglobulin (Ig) levels. As previously published, 10 patients with HIE had markedly higher levels of anti-S. aureus IgE than did 5 patients with eczema and recurrent superficial S. aureus infections (P less than 0.001). The HIE patients were also found to have a deficit of anti-S. aureus serum IgA as compared with 12 normal subjects, 12 patients with chronic granulomatous disease, 5 patients with chronic eczema and recurrent superficial S. aureus infections, and 3 patients with the Chediak-Higashi syndrome (P less than 0.01 for each comparison). In addition the HIE patients had an excess of anti-S. aureus IgM as compared with normal subjects (P less than 0.01). An expected excess of anti-S. aureus IgG was absent. These abnormalities cannot be explained by variations of total serum Ig levels or by a general inability to produce antigen-specific IgA because levels of naturally occurring IgA antibody against Escherichia coli lipopolysaccharide and the antigens of the pneumococcal vaccine are normal. Parotid saliva from patients with HIE contained less salivary IgA per milligram of protein (P less than 0.01) and less salivary anti-S. aureus IgA per milligram of protein (P less than 0.05) than did normal controls. The incidence of infection at mucosal surfaces and adjacent lymph nodes correlated inversely with serum anti-S. aureus IgA (r = -0.647, P = 0.034), serum anti-S. aureus IgE (r = -0.731, P = 0.016), total serum IgE (r = -0.714, P = 0.020), and total serum IgD (r = -0.597, P = 0.049). These findings are evidence of a previously undescribed immunoregulatory defect in patients with HIE, which may contribute to the increased susceptibility to infection in this syndrome.
患有高免疫球蛋白E和反复感染综合征（HIE）的患者通常会频繁发生由金黄色葡萄球菌引起的皮肤和呼吸道感染。我们开发了一套酶联免疫吸附测定法，该方法使用固定在0.22微米滤膜上的完整金黄色葡萄球菌（伍德菌株）以及山羊抗人IgE、抗人IgD、抗人IgG、抗人IgA和抗人IgM的高特异性、亲和纯化酶结合物。这些试剂用于测定金黄色葡萄球菌特异性免疫球蛋白（Ig）水平。如先前发表的那样，10例HIE患者的抗金黄色葡萄球菌IgE水平明显高于5例患有湿疹和反复浅表金黄色葡萄球菌感染的患者（P<0.001）。与12名正常受试者、12名慢性肉芽肿病患者、5名慢性湿疹和反复浅表金黄色葡萄球菌感染患者以及3名切-东综合征患者相比，HIE患者还被发现抗金黄色葡萄球菌血清IgA缺乏（每次比较P<0.01）。此外，与正常受试者相比，HIE患者的抗金黄色葡萄球菌IgM过量（P<0.01）。未发现预期的抗金黄色葡萄球菌IgG过量。这些异常现象不能用血清总Ig水平的变化或产生抗原特异性IgA的一般能力来解释，因为针对大肠杆菌脂多糖和肺炎球菌疫苗抗原的天然存在的IgA抗体水平是正常的。HIE患者腮腺唾液中每毫克蛋白质所含的唾液IgA较少（P<0.01），每毫克蛋白质所含的唾液抗金黄色葡萄球菌IgA也较少（P<0.05），与正常对照相比。黏膜表面和相邻淋巴结的感染发生率与血清抗金黄色葡萄球菌IgA（r=-0.647，P=0.034）、血清抗金黄色葡萄球菌IgE（r=-0.731，P=0.016）、血清总IgE（r=-0.714，P=0.020）和血清总IgD（r=-0.597，P=0.049）呈负相关。这些发现证明HIE患者存在一种先前未描述的免疫调节缺陷，这可能导致该综合征中感染易感性增加。
