Berthelot Laureline, Monteiro Renato C
INSERM U699, Faculté Bichat, 16 rue Henri Huchard, 75018 Paris, France - Université Paris Diderot, Faculté de Médecine, Site Bichat, 16 rue Henri Huchard, 75890 Paris Cedex 18, France - Laboratoire d'Excellence Inflamex, Sorbonne Paris Cité, 75890 Paris Cedex 18, France.
Biol Aujourdhui. 2013;207(4):241-7. doi: 10.1051/jbio/2013022. Epub 2014 Mar 5.
Immunoglobulin A (IgA) nephropathy (N) is the most common form of primary glomerulonephritis in the world and one of the first cause of end-stage renal failure. IgAN is characterized by the accumulation in mesangial areas of immune complexes containing IgA1. While epidemiology and clinical studies of IgAN are well-established, the mechanism(s) underlying disease development is poorly understood. The pathogenesis of this disease involves the deposition of polymeric and undergalactosylated IgA1 in the mesangium. Quantitative and structural changes of IgA1 play a key role in the development of the disease, due to functional abnormalities of two IgA receptors: the FcαR (CD89) expressed by blood myeloid cells and the transferrin receptor (TfR1) on mesangial cells. Abnormal IgA induces release of soluble CD89, responsible for the formation of circulating IgA complexes. These complexes are trapped by the TfR1 that is overexpressed on mesangial cells in IgAN patients, inducing the expression of transglutaminase 2. This enzyme stabilises IgA deposits at the surface of mesangial cells. These cells are then activated, proliferate and produce proinflammatory cytokines, leading to the loss of renal function.
免疫球蛋白A（IgA）肾病（IgAN）是全球原发性肾小球肾炎最常见的形式，也是终末期肾衰竭的首要病因之一。IgAN的特征是含有IgA1的免疫复合物在系膜区蓄积。虽然IgAN的流行病学和临床研究已很成熟，但对其疾病发展的潜在机制了解甚少。该疾病的发病机制涉及多聚化和低半乳糖基化IgA1在系膜中的沉积。IgA1的定量和结构变化在疾病发展中起关键作用，这是由于两种IgA受体存在功能异常：血液髓细胞表达的FcαR（CD89）和系膜细胞上的转铁蛋白受体（TfR1）。异常IgA诱导可溶性CD89释放，后者负责循环IgA复合物的形成。这些复合物被IgAN患者系膜细胞上过表达的TfR1捕获，诱导转谷氨酰胺酶2表达。该酶使IgA沉积物在系膜细胞表面稳定。然后这些细胞被激活、增殖并产生促炎细胞因子，导致肾功能丧失。
