What is IgE nephropathy in children?

First, the cause of IgA nephropathy in children

First, the cause of the disease

The cause is not very clear, and a variety of factors. Most scholars believe that this disease is containing IgA circulating immune complex in the kidney deposition and disease. Antigens in the complex may be associated with certain components of the virus, bacteria, or food that are infected with the respiratory tract or gastrointestinal mucosa.

Second, the pathogenesis

IgA nephropathy is an immune complex nephritis due to the deposition of IgA, C3 and / or IgA, IgG in renal tissue. The pathogenesis is IgA, which is closely related to IgA immune abnormality. At present, the study has deepened into IgA molecular structure Level.

(1) the structure and characteristics of immunoglobulin A: IgA is an important immunoglobulin, accounting for about 15.2% of total serum immunoglobulin, 80% of serum IgA is a single form of four chains, monomer The connection between the disulfide bond and the J chain is stable. IgA is divided into two serotypes, namely, IgA1 and IgA2, depending on the heavy chain antigenicity. IgA1 is the main subtype of serum, accounting for 80% to 90%, IgA2 only 10% to 20%. IgA2 and IgA2m (2), although serum IgA2 concentration and IgA1 only 1/4, but the secretion of 1gA2 concentration and IgA1 equal. In the structure of IgA2m (1), there is no disulfide bond between the chain and the light chain, but it is connected by noncovalent bond between the light chain and the chain. Another form of IgA is called secretory IgA (SIgA), which is present in human exudates such as saliva, tears, intestinal secretions, and colostrum. Secretory IgA differs from serotype in that it is a dimeric molecule that carries a J-chain and another exocrine component (SC), consisting of (IgA) 2-J-SC complex. While the serotype is (IgA) 2-J composition. J chain consists of 137 amino acids, molecular weight 1500, is an acidic glycoprotein, containing 8 cysteine ​​residues, 6 and intra-chain disulfide bond formation, and two linked to the chain. The C-terminus of the known chain has 18 additional amino acid residues that are linked to the chain by the second cysteine ​​residue at the C-terminus of the chain. Both are produced by plasma cells and are connected together when secreted. SC is synthesized by epithelial cells in the mucosal tissue or secretory glands and is linked by one of the two monomers IgA of the disulfide bond to human SIgA. SC is a polypeptide chain consisting of 549 to 558 amino acids with a molecular weight of about 7 Million, sugar content of up to 20%. There are five homologous regions on the polypeptide chain, each of which is composed of 104,114 amino acids, which are similar in structure to Ig in stereochemistry. It is known that the connection to the chain is in the Fc area, but the precise positioning is not clear. The configuration of SIgA may be: (1) a Y-type arrangement of stacking; ② the end of the end of the arrangement, the two IgA through the Fc area connected to form a double Y-shaped structure. (IgA) 2-J is produced by: (1) binding to SC on the basal side of epithelial cells to form IgA-J-SC, which is transferred to the top surface of a vesicle and secreted; (2) 2-J through the lymphatic vessels into the blood circulation, with the surface of the liver cells SC and clear, and then through the hepatocyte vesicle mechanism and turn into the bile duct, the end of the interconnection can form the end of the open multi-polymer, and an obvious feature Is multimeric size heterogeneity, serum IgA 20% is in the form of multimeric, and the sedimentation coefficient of 10s, 13s, 15s range, in addition to IgA easy to form complex with other protein tendencies, This is due to the chain of amino acid residues easily formed between the molecules of disulfide bonds. These properties of IgA molecular structure are important in the development of IgA nephropathy.

(2) deposition of IgA in the glomerular mesangial area: IgA nephropathy, IgA deposition in a manner consistent with the pathological changes of glomeruli. Mesangial area of ​​IgA deposition accompanied by mesangial proliferation, capillary deposition is accompanied by changes in vascular endothelium. IgA deposition caused by pathological factors are: ① antigen from the mucous membrane into the body and stimulate the immune system, the antigen composition is broad, including microbes, food (ovalbumin, bovine serum albumin, casein) and so on. ②IgA immune response abnormalities lead to high molecular weight poly-IgA formation. ③ IgA-fibronectin complexes in serum are found to be characteristic of IgA nephropathy by intravenous (IgA), receptor (FeaR) or fibronectin binding to deposition in the kidney. ④ other IgA clearance mechanism (such as liver) damage or saturation. The existing studies have shown that IgA in IgA nephropathy in the glomerular deposition of IgA is mainly poly-IgA1, IgA nephropathy in patients with serum IgA1, poly IgA, -IgA1 levels were seen increased. Patients with B cells present a deficiency of -1,3-galactosyltransferase (-1,3GT), resulting in reduced end-linked galactose at the time of IgA1 hinge region O-glycosylation, which may affect IgA1 and hepatocytes (ASGPR) binding to the clearance of IgA, and can increase its binding to kidney tissue deposition. Harpel and other in situ hybridization techniques found that IgA nephropathy intestinal mucosal expression of synthetic poly-IgA essential components J chain mRNA levels decreased, while the bone marrow is increased. In addition, tonsil PIgA1 production also increased. Because PIgA production is much lower than mucosal and bone marrow, PIgAl deposited in renal tissue may be mainly derived from bone marrow rather than tonsils and mucosa.

(3) Immunological abnormalities of IgA nephropathy: extensive studies of humoral and cellular immunity in IgA nephropathy suggest that there are immunological abnormalities in patients with IgA nephropathy, including: (1) autoantibodies: Fornesier et al. Have been found in patients with nephropathy for renal mesangial cells The macromolecular component of the antibody. In addition to the basement membrane Ⅰ, Ⅱ, Ⅲ type collagen fiber mucin, Gliadin and other components of the antibody. IgA-type anti-neutrophil cytoplasmic antibodies (IgA-ANCA) were also found in the blood of some patients. IgA nephropathy after renal transplantation in the transplanted kidney re-emergence of IgA nephropathy pathological changes as high as 40% to 50%, these data show that autoantibodies in IgA nephropathy play an important role in the pathogenesis. ② cellular immunity: studies have shown that cellular immune dysfunction also plays an important role in the pathogenesis of IgA nephropathy. IgA-specific inhibition of T cell activity leads to an increase in B lymphocyte synthesis IgA. T helper cells (Th) increased in the active phase of IgA nephropathy, so the activity of Th / Ts increased. T cells with IgA-specific receptors are called T cells, and T cells have the effect of increasing IgA production. It was found that IgA nephropathy, especially in patients with gross hematuria T increased significantly, T helper cells increased significantly led to increased IgA synthesis. ③ cytokines and inflammatory mediators: many cytokines involved in the regulation of the immune system, including lymphokines, interleukin (IL), tumor necrosis factor, peptide growth factor, these cytokines play an important role in the exercise of normal immune function, Abnormal circumstances will lead to disorders of the cytokine network, resulting in immune damage. In the process of glomerular mesangial cell proliferation, cytokines play an important role in inflammatory mediators (complement components MAC, IL-1, MCP-1, reactive oxygen species). ④ immune genetic: family members have been suffering from IgA nephropathy reported that prompted genetic factors in IgA nephropathy has an important role. IgA nephropathy-related HLA antigen sites are also reported, Europe and the United States to Bw35, Japan and China to DR4 more common, there are reports of northern China Han DRWl2 most common, in addition to B12, DR1 and IL-RN.2 Gene, ACED / D genotype.

2. Pathological changes in the characteristics of light microscopic glomerular mesangial proliferation, the degree from the focal, segmental hyperplasia to diffuse mesangial proliferation. Part of the mesangial hyperplasia can be seen more mesenteric insertion, the formation of segmental dual-track. Sometimes see segmental glomerulosclerosis, capillary collapse, balloon adhesions. Individual cases of severe lesions can occur transparent, global hardening, individual capillary necrosis and crescent formation. Masson staining shows a large number of retrogradic red sediments in the mesangial area, and these sediments have diagnostic value. The expressions of type Ⅰ, Ⅲ, Ⅳ collagen and laminin and fibronectin in glomerular capillary loop of IgA nephropathy were significantly increased, and the expression of type Ⅰ and Ⅲ collagen in mesangial area was also increased. Most patients had renal tubular basement membrane Ⅳ Type collagen expression also increased. Electron microscopy mainly for different degrees of mesangial cells and matrix hyperplasia, in the mesangial area with more electron dense material deposition, some dense matter can also be deposited in the subcutaneous. In recent years, the glomerular basement membrane ultrastructural changes, 10% of IgA nephropathy with basement membrane thinning, whether it is combined with thin basement membrane disease or IgA nephropathy secondary change is not clear. WHO on the pathology of the disease classification:

(1) Ⅰ: light microscope, the majority of glomerular normal, a small number of parts of mild mesangial hyperplasia with (not accompanied by) cell proliferation, called minor changes, no tubules and interstitial damage.

(2) Ⅱ grade: less than 50% of the glomerular mesangial proliferation, rare sclerosis, adhesions and small crescent, said mild lesions, no tubules and interstitial damage.

(3) Ⅲ grade: focal segment and even diffuse glomerular mesangial hyperplasia with cell proliferation, occasional adhesion and small crescent, called focal segmental glomerulonephritis. Occasional focal interstitial edema and mild inflammatory cell infiltration.

(4) Ⅳ grade: all glomerular obvious diffuse mesangial proliferation and sclerosis, with irregular distribution, varying degrees of cell proliferation, often seen abandoned glomeruli. Less than 50% of glomeruli have adhesions and crescent bodies, called diffuse mesangial proliferative glomerulonephritis. There are obvious tubule atrophy and interstitial inflammation.

(5) Ⅴ grade: similar to the grade Ⅳ but more severe, segmental and / or sclerosis, vitreous changes, balloon adhesions, more than 50% of the glomerular crescent, known as diffuse hardening glomerulus nephritis. Tubular and interstitial damage is more severe than grade IV.