van der Molen Renate G, Hamann Dörte, Jacobs Joannes F M, van der Meer Arnold, de Jong Jan, Kramer Christine, Strengers Paul F W, van der Meer Jos W M
Department of Laboratory Medicine, Laboratory for Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands.
Department of Immunopathology and Blood Coagulation, Sanquin Diagnostic Services, Amsterdam, the Netherlands.
Transfusion. 2015 Apr;55(4):832-7. doi: 10.1111/trf.12922. Epub 2014 Nov 13.
Anti-SSA autoantibodies are among the most frequently detected autoantibodies and have traditionally been associated with Sjögren's syndrome (SjS) and systemic lupus erythematosus. The unexpected finding of anti-SSA antibodies in a patient with common variable immunodeficiency disorder (CVID) treated with intravenous immunoglobulin (IVIG), who developed discoid lupus erythematosus, prompted us to investigate the presence of anti-SSA antibodies in IVIG preparations. Since anti-SSA antibodies may be present in apparently healthy individuals without overt autoimmune features, IVIG preparations may also contain anti-SSA antibodies.
IVIG consists of polyclonal immunoglobulin G isolated from the plasma of more than 1000 blood donors. Several IVIG batches from different suppliers and serum samples of patients receiving these IVIG products were tested for the presence of anti-nuclear antibodies (ANAs) and extractable nuclear antibodies (ENAs). In addition, we tested several plasma pools for the presence of anti-SSA and subsequent serum samples of individual donors.
Several CVID-patients receiving IVIG tested positive for ANA and anti-SSA. The IVIG products administered also contained clearly detectable concentrations of these antibodies. The frequency of apparently healthy blood donors with anti-SSA positivity was 0.69% and one of 1894 donors (0.05%) showed a very high titer of anti-SSA of more than 10,000 U/mL.
Anti-SSA is present in IVIG products and in blood donors without clinical symptoms. IVIG replacement can interfere with ANA and ENA serology by passive transfer of autoantibodies. We hypothesize that such autoantibodies may be causally related to disease manifestations in some recipients.
抗SSA自身抗体是最常检测到的自身抗体之一,传统上与干燥综合征(SjS)和系统性红斑狼疮相关。一名接受静脉注射免疫球蛋白(IVIG)治疗的常见可变免疫缺陷病(CVID)患者出现盘状红斑狼疮,意外检测到抗SSA抗体,这促使我们调查IVIG制剂中抗SSA抗体的存在情况。由于抗SSA抗体可能存在于无明显自身免疫特征的健康个体中,IVIG制剂也可能含有抗SSA抗体。
IVIG由从1000多名献血者血浆中分离出的多克隆免疫球蛋白G组成。对来自不同供应商的几批IVIG以及接受这些IVIG产品的患者血清样本进行抗核抗体(ANA)和可提取核抗原(ENA)检测。此外,我们还检测了几个血浆池以及个别献血者随后的血清样本中抗SSA的存在情况。
几名接受IVIG治疗的CVID患者ANA和抗SSA检测呈阳性。所使用的IVIG产品中也含有可清晰检测到浓度的这些抗体。抗SSA阳性的健康献血者频率为0.69%,1894名献血者中有1名(0.05%)抗SSA滴度非常高,超过10000 U/mL。
IVIG产品和无临床症状的献血者中存在抗SSA。IVIG替代治疗可通过自身抗体的被动转移干扰ANA和ENA血清学检测。我们推测这种自身抗体可能与某些接受者的疾病表现存在因果关系。