School of Pharmacy and Biochemistry, University of Buenos Aires (UBA) and Prof. Ricardo A. Margni Humoral Immunity Institute (IDEHU), National Research Council (CONICET)-UBA, Buenos Aires, Argentina.
Nutrition Service, J. P. Garrahan National Pediatrics Hospital, Buenos Aires, Argentina.
PLoS One. 2013 Dec 30;8(12):e84099. doi: 10.1371/journal.pone.0084099. eCollection 2013.
In this study, the characterization of insulin (auto)antibodies has been described, mainly in terms of concentration (q), affinity (Ka) and Ig (sub)isotypes by Surface Plasmon Resonance (SPR) in two particular clinical cases of individuals with severe episodes of impaired glycemia. Subject 1 suffers from brittle diabetes associated with circulating insulin antibodies (IA) due to insulin treatment. Subject 2 has insulin autoantibodies (IAA) associated with hypoglycemia in spite of not being diabetic and not having ever received exogenous insulin therapy. After conventional screening for IA/IAA by radioligand binding assay (RBA), we further characterized IA/IAA in sera of both patients in terms of concentration (q), affinity (Ka) and Ig (sub)isotypes by means of SPR technology. In both cases, q values were higher and Ka values were lower than those obtained in type 1 diabetic patients, suggesting that IA/IAA:insulin immunocomplexes could be responsible for the uncontrolled glycemia. Moreover, subject 1 had a predominat IgG1 response and subject 2 had an IgG3 response. In conclusion, SPR technology is useful for the complete characterization of IA/IAA which can be used in special cases where the simple positive/negative determination is not enough to achieve a detailed description of the disease fisiopathology.
在这项研究中,主要通过表面等离子体共振(SPR)技术,从浓度(q)、亲和力(Ka)和免疫球蛋白(sub)亚型等方面对 2 例严重血糖受损发作的个体的胰岛素(自身)抗体进行了特征描述。病例 1 患有脆性糖尿病,与胰岛素治疗相关的循环胰岛素抗体(IA)有关。病例 2 尽管没有糖尿病且从未接受过外源性胰岛素治疗,但存在与低血糖相关的胰岛素自身抗体(IAA)。通过放射配体结合分析(RBA)对 IA/IAA 进行常规筛选后,我们进一步通过 SPR 技术从浓度(q)、亲和力(Ka)和免疫球蛋白(sub)亚型等方面对这 2 例患者的 IA/IAA 进行了特征描述。在这两种情况下,q 值均高于 1 型糖尿病患者,Ka 值均低于 1 型糖尿病患者,这表明 IA/IAA:胰岛素免疫复合物可能是导致血糖失控的原因。此外,病例 1 表现出以 IgG1 为主的反应,病例 2 则表现出 IgG3 反应。总之,SPR 技术可用于对 IA/IAA 进行全面特征描述,在某些特殊情况下,简单的阳性/阴性测定不足以详细描述疾病的病理生理学。