Tatum A H, Bollinger R R, Sanfilippo F
Transplantation. 1984 Dec;38(6):582-6. doi: 10.1097/00007890-198412000-00006.
Although the use of antithymocyte globulin/antilymphocyte serum (ATG/ALS) has been shown to be beneficial in treating renal allograft rejection, the incidence and nature of serum sickness reactions following such treatment have received limited attention. In the setting of rejection or infection, the diagnosis of serum sickness is often difficult on clinical grounds, and biopsy may be an undesirable means of obtaining documentation. A sensitive enzyme-linked immunosorbent assay (ELISA) was developed to detect antibodies against ATGAM (Upjohn) and was utilized in 35 patients treated for rejection with ATGAM following clinical unresponsiveness to bolus methylprednisolone therapy. Serum sickness was diagnosed clinically in 7 of these patients (20%) during or immediately following ATGAM therapy. Significant titers of anti-ATGAM antibody were found in these 7 cases, as well as 5 additional cases (14%). Upon retrospective review, the diagnosis of serum sickness was also made in each of these 5 additional cases based upon the immunopathologic detection of horse immunoglobulin deposits in vessels of tissue (lung or kidney) examined. In 2 other cases where serologic testing was negative, there was some clinical suggestion of serum sickness that could not be documented pathologically. ELISA for anti-ATGAM antibodies was negative in testing 46 control patients and pooled normal sera. In one case, retrospective testing of pre-ATGAM therapy serum samples showed significant antihorse antibodies. Despite a negative skin test prior to administration, this patient developed symptoms of serum sickness 15 days after the onset of ATGAM therapy. Extremely high titers of antibody were detected 5 days earlier (10 days posttherapy), and the presence of horse immunoglobulin immune complexes in the kidney was documented following graft loss that occurred within 4 weeks. These findings indicate (1) serologic testing for anti-ATGAM antibodies using a sensitive ELISA method provides a quick, inexpensive, noninvasive means for the presumptive diagnosis of serum sickness in complicated clinical situations, and (2) screening of patient sera prior to administration of ATGAM may be useful in avoiding potential serum sickness reactions.
尽管抗胸腺细胞球蛋白/抗淋巴细胞血清（ATG/ALS）已被证明在治疗肾移植排斥反应中有益，但这种治疗后血清病反应的发生率和性质受到的关注有限。在排斥反应或感染的情况下，基于临床依据往往难以诊断血清病，而活检可能是获取诊断依据的不理想方法。我们开发了一种敏感的酶联免疫吸附测定（ELISA）来检测抗ATGAM（Upjohn）抗体，并将其应用于35例对大剂量甲基泼尼松龙治疗无临床反应后接受ATGAM治疗排斥反应的患者。在这些患者中，有7例（20%）在ATGAM治疗期间或治疗后立即被临床诊断为血清病。在这7例以及另外5例（14%）患者中发现了显著滴度的抗ATGAM抗体。经回顾性分析，基于在检查的组织（肺或肾）血管中检测到马免疫球蛋白沉积，这另外5例患者也均被诊断为血清病。在另外2例血清学检测为阴性的病例中，有一些血清病的临床迹象，但无法通过病理检查证实。在检测46例对照患者和混合正常血清时，抗ATGAM抗体的ELISA检测结果为阴性。在1例病例中，对ATGAM治疗前的血清样本进行回顾性检测显示存在显著的抗马抗体。尽管在给药前皮肤试验为阴性，但该患者在ATGAM治疗开始15天后出现了血清病症状。在治疗后10天（即症状出现5天前）检测到极高滴度的抗体，并且在4周内发生移植肾丢失后，证实肾脏中存在马免疫球蛋白免疫复合物。这些发现表明：（1）使用敏感的ELISA方法检测抗ATGAM抗体为在复杂临床情况下初步诊断血清病提供了一种快速、廉价且非侵入性的手段；（2）在给予ATGAM之前筛查患者血清可能有助于避免潜在的血清病反应。
