Department of Tranzo, Tilburg University, Tilburg, the Netherlands.
Department of Paediatrics, Amalia Children's Hospital, Nijmegen, the Netherlands.
Clin Exp Immunol. 2021 Aug;205(2):213-221. doi: 10.1111/cei.13605. Epub 2021 Jun 1.
Unlike immunoglobulin (Ig)G pneumococcal polysaccharide (PnPS)-antibodies, PnPS IgA and IgM-antibodies are not routinely determined for the assessment of immunocompetence. It is not yet known whether an isolated inability to mount a normal IgM or IgA-PnPS response should be considered a relevant primary antibody deficiency (PAD). We studied the clinical relevance of anti-PnPS IgM and IgA-assays in patients with suspected primary immunodeficiency in a large teaching hospital in 's-Hertogenbosch, the Netherlands. Serotype-specific-PnPS IgG assays were performed; subsequently, 23-valent-PnPS IgG assays (anti-PnPS IgG assays), and later anti-PnPS IgA and IgM assays, were performed in archived material (240 patients; 304 samples). Eleven of 65 pre- and six of 10 post-immunization samples from good responders to PnPS serotype-specific IgG testing had decreased anti-PnPS IgA and/or IgM titres. Of these, three pre- and no post-immunization samples were from patients previously classified as 'no PAD'. Determination of anti-PnPS IgA and IgM in addition to anti-PnPS IgG did not reduce the need for serotype-specific PnPS IgG testing to assess immunocompetence [receiver operating characteristic (ROC) analysis of post-immunization samples: anti-PnPS IgA + IgG area under the curve (AUC) = 0.80, 95% confidence interval (CI) = 0.63-0.97; anti-PnPS IgM + IgG AUC 0.80, 95% CI = 0.62-0.98; anti-PnPS IgA + IgG + IgM AUC = 0.71, 95% CI = 0.51-0.91; anti-PnPS IgG AUC = 0.93, 95% CI = 0.85-1.00]. Our data show that patients classified as having an intact antibody response based on measurement of serotype-specific PnPS IgG can still display impaired anti-PnPS IgM and IgA responses, and that the additional measurement of anti-PnPS IgA and IgM could not reduce the need for serotype-specific IgG testing. Future studies are needed to investigate the clinical relevance of potential 'specific IgA or IgM antibody deficiency' in patients with recurrent airway infections in whom no PAD could be diagnosed according to the current definitions.
与免疫球蛋白 (Ig)G 肺炎球菌多糖 (PnPS)-抗体不同，PnPS IgA 和 IgM-抗体通常不用于评估免疫能力。目前尚不清楚是否应将单独缺乏正常 IgM 或 IgA-PnPS 反应视为相关的原发性抗体缺陷 (PAD)。我们在荷兰's-Hertogenbosch 的一家大型教学医院研究了疑似原发性免疫缺陷患者中抗 PnPS IgM 和 IgA 检测的临床相关性。进行了血清型特异性 PnPS IgG 检测；随后，在存档材料中进行了 23 价 PnPS IgG 检测（抗 PnPS IgG 检测），随后进行了抗 PnPS IgA 和 IgM 检测（240 例患者；304 份样本）。11 份良好 PnPS 血清型特异性 IgG 检测反应者的预免疫和 6 份后免疫样本的抗 PnPS IgA 和/或 IgM 滴度降低。其中，3 份预免疫样本和 10 份后免疫样本来自先前被归类为“无 PAD”的患者。除了抗 PnPS IgG 外，测定抗 PnPS IgA 和 IgM 并不能减少对血清型特异性 PnPS IgG 检测评估免疫能力的需求[后免疫样本的受试者工作特征 (ROC) 分析：抗 PnPS IgA+IgG 曲线下面积 (AUC) = 0.80，95%置信区间 (CI) = 0.63-0.97；抗 PnPS IgM+IgG AUC 0.80，95% CI = 0.62-0.98；抗 PnPS IgA+IgG+IgM AUC = 0.71，95% CI = 0.51-0.91；抗 PnPS IgG AUC = 0.93，95% CI = 0.85-1.00]。我们的数据表明，根据血清型特异性 PnPS IgG 测量被归类为具有完整抗体反应的患者仍可能显示出受损的抗 PnPS IgM 和 IgA 反应，并且额外测量抗 PnPS IgA 和 IgM 不能减少对血清型特异性 IgG 检测的需求。未来的研究需要调查在根据当前定义无法诊断为 PAD 的反复呼吸道感染患者中，潜在的“特异性 IgA 或 IgM 抗体缺陷”的临床相关性。
