Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Semin Immunopathol. 2015 Mar;37(2):187-97. doi: 10.1007/s00281-014-0466-0. Epub 2014 Nov 18.
Increased incidence of fungal infections in the immunocompromised individuals and fungi-mediated allergy and inflammatory conditions in immunocompetent individuals is a cause of concern. Consequently, there is a need for efficient therapeutic alternatives to treat fungal infections and inflammation. Several studies have demonstrated that antibodies or immunoglobulins have a role in restricting the fungal burden and their clearance. However, based on the data from monoclonal antibodies, it is now evident that the efficacy of antibodies in fungal infections is dependent on epitope specificity, abundance of protective antibodies, and their isotype. Antibodies confer protection against fungal infections by multiple mechanisms that include direct neutralization of fungi and their antigens, inhibition of growth of fungi, modification of gene expression, signaling and lipid metabolism, causing iron starvation, inhibition of polysaccharide release, and biofilm formation. Antibodies promote opsonization of fungi and their phagocytosis, complement activation, and antibody-dependent cell toxicity. Passive administration of specific protective monoclonal antibodies could also prove to be beneficial in drug resistance cases, to reduce the dosage and associated toxic symptoms of anti-fungal drugs. The longer half-life of the antibodies and flexibilities to modify their structure/forms are additional advantages. The clinical data obtained with two monoclonal antibodies should incite interests in translating pre-clinical success into the clinics. The anti-inflammatory and immunoregulatory role of antibodies in fungal inflammation could be exploited by intravenous immunoglobulin or IVIg.
免疫功能低下个体中真菌感染的发生率增加,以及免疫功能正常个体中真菌介导的过敏和炎症状态,这令人担忧。因此,需要有效的治疗方法来治疗真菌感染和炎症。多项研究表明,抗体或免疫球蛋白在限制真菌负荷及其清除方面发挥作用。然而,基于单克隆抗体的数据,现在很明显,抗体在真菌感染中的疗效取决于表位特异性、保护性抗体的丰度及其同型。抗体通过多种机制发挥抗真菌作用,包括直接中和真菌及其抗原、抑制真菌生长、改变基因表达、信号和脂质代谢,导致缺铁、抑制多糖释放和生物膜形成。抗体促进真菌的调理作用和吞噬作用、补体激活和抗体依赖性细胞毒性。特异性保护性单克隆抗体的被动给药也可能在耐药病例中证明是有益的,可以减少抗真菌药物的剂量和相关的毒副作用。抗体的半衰期更长,结构/形式更灵活,这是额外的优势。从两种单克隆抗体获得的临床数据应该激发将临床前成功转化为临床的兴趣。抗体在真菌性炎症中的抗炎和免疫调节作用可以通过静脉注射免疫球蛋白或 IVIg 来利用。