Pediatric IgA Nephropathy

Introduction to Pediatric IgA Nephropathy basic knowledge The proportion of children: the incidence rate of children is about 0.02%-0.05%

Pediatric IgA nephropathy

(1) Causes of the disease

(two) pathogenesis

Pathogenesis

(1) Structure and characteristics of immunoglobulin A: IgA is an important immunoglobulin, accounting for 15.2% of total serum immunoglobulin. 80% of serum IgA is in the form of four chains of monomers. The inter-ligation is stabilized by the disulfide bond and the J chain. IgA is divided into two serotypes according to the antigenicity of the alpha heavy chain, namely IgA1 and IgA2. IgA1 is the main subtype in serum, accounting for 80% to 90%, IgA2. Only 10% to 20%, IgA1 hinge region is 1 times longer than IgA2, IgA2 can be divided into IgA2m (1) and IgA2m (2), although serum IgA2 concentration is only 1/4 of IgA1, but 1gA2 in secretion The concentration is equal to that of IgA1. In the structure of IgA2m(1), there is no disulfide bond between the chain and the light chain, and it is connected by a non-covalent bond, but the disulfide bond is connected between the light chain and the chain, and the other is The form of IgA is called secretory IgA (SIgA) and is present in human exocrines such as saliva, tears, intestinal secretions and colostrum. Secretory IgA is a dimeric molecule, unlike serotypes. One J chain and another exocrine component (SC) constitute the (IgA)2-J-SC complex, while the serotype is composed of (IgA)2-J. The J chain consists of 137 amino acids with a molecular weight of 1500. An acidic glycoprotein containing 8 cystine residues, 6 associated with intrachain disulfide bond formation, and 2 associated with alpha chain linkage, 18 additional amino acid residues at the C-terminus of the known alpha chain The J chain is linked to the chain by a second cysteine esidue at the C-terminus of the chain, both of which are produced by plasma cells and are joined together at the time of secretion, and SC is composed of mucosa. The epithelial cells in the tissue or secretory glands are synthesized and linked to one of the two monomeric IgAs of human SIgA by a disulfide bond. SC is a polypeptide chain consisting of 549-558 amino acids with a molecular weight of about 70,000. The content is up to 20%, there are 5 homologous regions on the polypeptide chain, and each homologous region is composed of 104, 114 amino acids. These homologous regions are similar to Ig in stereo structure, and it is known that the linkage to the chain is The Fc region, but the precise localization is not clear. The configuration of SIgA may be: 1 a Y-shaped arrangement of a stack; 2 end-to-end arrangement, two IgAs connected by an Fc region, forming a double Y-shaped Structure, local tissue plasma cells (IgA) 2-J pass: 1 after binding to SC on the basal side surface of epithelial cells

(2) Deposition of IgA in the mesangial area: In IgA nephropathy, the deposition of IgA is parallel to the pathological changes of glomeruli. IgA deposition in the mesangial area is accompanied by mesangial hyperplasia, on the capillaries. Sedimentation is accompanied by changes in vascular endothelium. Pathological factors that cause IgA deposition are: 1 antigen enters the body from the mucosa and stimulates the IgA immune system. The antigenic components range from microorganisms to food (ovalbumin, bovine serum albumin, casein). Etc., 2IgA immunoreactivity leads to the formation of high molecular weight poly IgA, and 3 antigen-binding poly IgA is deposited in the kidney by electrostatic ( chain), receptor (FeaR) or binding to fibronectin. IgA has been found in serum. - Fibronectin complex is characteristic of IgA nephropathy, 4 other IgA clearance mechanisms (such as liver) are damaged or saturated. Existing studies have shown that IgA deposited in glomeruli in IgA nephropathy is mainly poly-. -IgA1, IgA1 patients with serum IgA1, poly IgA, -IgA1 levels can be seen increased, patient B cells have -1,3 galactosyltransferase (-1,3GT) defects, resulting in IgA1 hinge O-glycosylation

2. Pathological changes

Light microscopy showed mesangial mesangial hyperplasia, ranging from focal, segmental hyperplasia to diffuse mesangial hyperplasia. Some mesangial hyperplasia can be seen in mesangial insertion, forming segmental double-track, sometimes see Segmental glomerular sclerosis, capillary collapse, balloon adhesion, individual lesions may appear transparent, global hardening, individual capillary necrosis and crescent formation, Masson staining can be seen in the mesangial area Reddish sediments, these deposits have diagnostic value, type I, III, IV collagen and laminin, fibronectin increased in IgA nephropathy glomerular capillary vasospasm, type I, III collagen in the mesangial area The expression also increased significantly. In most patients, the expression of type IV collagen in the basement membrane of renal tubules also increased. Under electron microscope, there were mainly mesangial cells and stromal hyperplasia in different degrees. There were more electron dense deposits in the mesangial area, and some dense substances could also be used. Deposition under the endothelium, in recent years, the ultrastructure of the glomerular basement membrane has also changed, about 10% of IgA nephropathy has a basement membrane thinning, whether it is associated with thin basement membrane disease or IgA nephropathy

Pediatric IgA nephropathy prevention

Pediatric IgA nephropathy complications