Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Nijmegen, Netherlands.
Radboud Center for Infectious Diseases, Nijmegen, Netherlands.
Front Immunol. 2018 Aug 23;9:1925. doi: 10.3389/fimmu.2018.01925. eCollection 2018.
Patients with primary immunoglobulin deficiency have lower immunoglobulin levels or decreased immunoglobulin function, which makes these patients more susceptible to bacterial infection. Most prevalent are the selective IgA deficiencies (1:3,000), followed by common variable immune deficiency (1:25,000). Agammaglobulinemia is less common (~1:400,000) and is characterized by very low or no immunoglobulin production resulting in a more severe disease phenotype. Therapy for patients with agammaglobulinemia mainly relies on prophylactic antibiotics and the use of IgG replacement therapy, which successfully reduces the frequency of invasive bacterial infections. Currently used immunoglobulin preparations contain only IgG. As a result, concurrent IgA and IgM deficiency persist in a large proportion of agammaglobulinemia patients. Especially patients with IgM deficiency remain at risk for recurrent infections at mucosal surfaces, which includes the respiratory tract. IgA and IgM have multiple functions in the protection against bacterial infections at the mucosal surface. Because of their multimeric structure, both IgA and IgM are able to agglutinate bacteria efficiently. Agglutination allows for entrapment of bacteria in mucus that increases clearance from the respiratory tract. IgA is also important for blocking bacterial adhesion by interfering with bacterial adhesion receptors. IgM in its place is very well capable of activating complement, therefore, it is thought to be important in complement-mediated protection at the mucosal surface. The purpose of this Mini Review is to highlight the latest advances regarding IgA- and IgM-enriched immunoglobulin replacement therapy. We describe the different IgA- and IgM-enriched IgG formulations, their possible modes of action and potential to protect against respiratory tract infections in patients with primary immunoglobulin deficiencies.
原发性免疫球蛋白缺陷患者的免疫球蛋白水平较低或免疫球蛋白功能下降，这使这些患者更容易受到细菌感染。最常见的是选择性 IgA 缺乏症（1:3000），其次是常见可变免疫缺陷症（1:25000）。无丙种球蛋白血症较少见（~1:400000），其特征是几乎或完全不能产生免疫球蛋白，导致更严重的疾病表型。无丙种球蛋白血症患者的治疗主要依赖预防性抗生素和 IgG 替代疗法，这成功降低了侵袭性细菌感染的频率。目前使用的免疫球蛋白制剂仅含有 IgG。因此，在很大一部分无丙种球蛋白血症患者中，同时存在 IgA 和 IgM 缺乏症持续存在。特别是 IgM 缺乏症患者仍有复发性感染的风险，包括呼吸道感染。IgA 和 IgM 在保护粘膜表面免受细菌感染方面具有多种功能。由于其多聚体结构，IgA 和 IgM 都能够有效地聚集细菌。聚集使细菌被困在粘液中，从而增加了从呼吸道清除的速度。IgA 还通过干扰细菌粘附受体来阻止细菌粘附，从而发挥重要作用。IgM 同样能够有效地激活补体，因此，它被认为在粘膜表面的补体介导保护中很重要。本综述的目的是强调 IgA 和 IgM 丰富的免疫球蛋白替代疗法的最新进展。我们描述了不同的 IgA 和 IgM 丰富的 IgG 制剂、它们可能的作用机制以及在原发性免疫球蛋白缺陷患者中预防呼吸道感染的潜力。
