IgA nephritis is caused by what?
The cause is not very clear, with a variety of factors. Most scholars believe that this disease is to contain IgA circulating immune complexes deposited in the kidney and disease. Complex antigen may be infected with respiratory or gastrointestinal mucosa viruses, bacteria, or food ingredients.
(B) in the pathogenesis
. Pathogenesis of renal tissue of IgA, C3, and (or) IgA, IgG deposition, IgA nephropathy is an immune complex glomerulonephritis, the incidence of IgA immune disorders are closely related, the present study has depth to IgA molecular structure level.
(1) the structure and characteristics of immunoglobulin A: IgA is an important immune globulin, accounting for 15.2% of the total serum immunoglobulin, 80% of serum IgA in the form of the monomer four chain monomer The inter-connected by disulfide bonds and the stability of the J chain. By α heavy chain different antigenic IgA is divided into two serotypes, i.e., IgA1 and IgA2.
IgA1 is the main subtype in the serum, accounting for 80% ~ 90%, IgA2, only 10% to 20%. IgA1 hinge region is 1 times longer than IgA2 IgA2 can be divided into the the IgA2m (1) and the IgA2m (2), although the concentration in serum IgA2 only IgA1 1/4, but the secretion of fluid equal to the 1gA2 concentration IgA1. Structure IgA2m (1) alpha chain and light chain disulfide bonds, connected to rely on non-covalent bonds, but between the light chain and α chain disulfide bonds connected.
Another form of IgA called secretory IgA (SIgA) exist in the outer secretions, such as saliva, tears, intestinal secretions and colostrum. Secretory IgA and serotype different, it is a dimeric molecule with a J chain, and the other outer secretory component (SC), composition (IgA) 2-J-SC complexes. Serotype is (IgA) 2-J composition.
J chain consists of 137 amino acids, molecular weight of 1500, is an acidic glycoprotein containing 8 cysteine residues, six with intra-chain disulfide bond formation, and the two with the connection of the α chain. 18 additional amino acid residues of the C-terminus of the known α chain, J chain is connected through the first two cysteine residues with an α-chain with the C-terminus of the α chain. Both of which are produced by plasma cells, and secretion would be connected together.
SC is synthesized by the epithelial cells in the mucosal tissue or endocrine body, connected through one of the two monomer IgA disulfide colleagues SIgA, SC is from 549 to 558 amino acids of the polypeptide chain, a molecular weight of about 7 Wan, glycosyl content of up to 20%. 5 homologous region in its polypeptide chain, each of the homologous region from the 104,114 amino acids, these homologous regions in the three-dimensional structure similar to and Ig. It has been known that is connected to the α-chain in the Fc region, but the precise positioning is not yet clear. The SIgA configuration may add up to the Y-shaped arrangement: ① a heap; ② The end of the end of the arrangement, the two IgA Fc α connected double Y-shaped structure.
Local tissue plasmacytomas (IgA) 2-J through the: ① with epithelial cell surface of the substrate side of the SC combination formed IgA-J-SC, and transferred to the top surface of a vesicle and secreted; ② (IgA) 2-J lymphatic vessels into the blood circulation, SC combined with the surface of the liver cells and clear, then turn to enter the biliary vesicle mechanism of liver cells, and eventually into the intestines.
The serum IgA terminal connected to each other may be formed to open at the end of polymer, and an obvious feature is a poly body size heterogeneity, the serum IgA 20% of polymer present in the form, and the sedimentation coefficient of 10s 13s, 15s ranging addition IgA Ease of a tendency to form a complex with other proteins, which are vulnerable due to the α-chain of the amino acid residues in the formation of intermolecular disulfide bonds. IgA molecular structure of these characteristics is important in IgA nephropathy.
(2) IgA deposition in the mesangial area: IgA nephropathy, IgA deposition and glomerular pathological changes parallel. Associated with mesangial proliferative mesangial IgA deposition, deposition on the capillary accompanied by changes of the vascular endothelial.
IgA deposition caused by pathological factors: ① antigen from the mucous membrane into the body and stimulate IgA immune system, the antigen component of a wide range of microorganisms, Food (ovalbumin, bovine serum albumin, casein), etc.. ② IgA immune response abnormalities lead to high molecular weight poly-IgA formation. (3) antigen-binding poly-IgA by electrostatic (λ chain), receptor (Fear) or connected to the fiber to protein binding and deposition in the kidneys, it has been found that the serum IgA-fibronectin complex is characterized IgA nephropathy. ④ Other IgA clearance mechanisms (such as liver) damage or saturation.
Existing studies show that the deposition in the glomeruli of the IgA IgA nephropathy is mainly poly λ-IgA1, the average IgA nephropathy patients, serum IgA1, poly-IgA, λ-IgA1 water visible increased. B cells in patients with reduced end link of galactose, β-1, 3 galactosyl transferase (β-1, 3GT) defects, resulting in O-glycosylation of IgA1 hinge region, this change may affect IgA1 and oligonucleotide on the sialic acid in the liver cell receptor (ASGPR) binding affect the clearance of IgA, but also increase the combined deposition and kidney tissue.
Harpel by in situ hybridization study found that of IgA nephropathy intestinal mucosa express an essential component of the synthesis of poly-IgA J chain mRNA levels decreased, while the bone marrow is increased. In addition tonsil PIgA1 also increased. The due production of tonsil PIgA is far lower than the mucosa and bone marrow, it is deposited in the kidney tissue PIgAl mainly derived from bone marrow rather than tonsils and mucosal.
(3) IgA nephropathy immune abnormalities: IgA nephropathy humoral and cellular immune extensive research shows that patients with IgA nephropathy immune abnormalities, including:
① autoantibodies: Fornesier, has been found in the serum of kidney patients the cytoplasmic macromolecules ingredients mesangial cells in the antibody. In addition to antibodies against the basement membrane Ⅰ, Ⅱ type III collagen fibers laminin, Gliadin ingredients. IgA anti-neutrophil cytoplasmic antibodies (IgA-ANCA) is also found in the blood of some patients. IgA nephropathy received renal allograft re-appear in the transplanted kidney the IgA nephropathy pathological changes by as much as 40% to 50%, these data are autoantibodies play an important role in the pathogenesis of IgA nephropathy.
② cellular immunity: studies have shown that the cellular immune function disorders are IgA nephropathy play an important role in the pathogenesis. IgA specific inhibition of the decline in the activity of T cells resulting in B lymphocytes increased synthesis of IgA. T helper cell (Th) of activity in IgA nephropathy increased activity of Th / Ts increased. IgA specific receptor of T cells referred to as a the Tα cell, Talpha cells increase the role of IgA production. It was found that IgA nephropathy, especially for patients with gross hematuria Tα increased significantly, Tα helper cells resulted in significantly increased IgA synthesis increased.
③ cell factor and inflammation of the media: many cytokines involved in the regulation of the immune system, including lymphokines White mediated hormone (interleukin, of IL), tumor necrosis factor, a polypeptide growth factor, these cytokines for the exercise of normal immune function from the important role in the abnormal circumstances will cause the offset of the cytokine network, thereby generating immune injury. Mesangial cell proliferation, cytokine and inflammatory mediators (complement components MAC, IL-1, MCP-1, reactive oxygen species, etc.) play an important role.
④ immune genetic: there are family members has suffering from IgA nephropathy reported, suggesting that genetic factors important role in IgA nephropathy. IgA nephropathy associated HLA antigen sites also reports vary, Europe and the United States Bw35, Japan and China DR4 common, also reported in northern China Han DRWl2 most common, in addition to B12, DR1 and IL-RN.2 bit gene, ACED / D genotype reported.
These sediments have diagnostic value. I, III, type IV collagen and laminin, fibronectin in IgA nephropathy glomerular capillary loop expression increased significantly, I type III collagen expression in mesangial area also increased significantly, the majority of patients with tubular basement IV also increased the expression of collagen type.
And accompanied by large lumpy electron dense deposits.