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Introduction to Several Autoimmune Disease-associated Antigens and Antibodies (II)

These complexes are located on the mitochondrial matrix and are connected to the inner mitochondrial membrane; use lipoamide prosthetic groups in the body and catalyze a variety of Oxidative decarboxylation of α-keto acid substrates. Although M2 subtype (AMA-M2) antibody detection is of great significance in the clinical diagnosis of primary biliary cirrhosis, it is not the only specific autoantibody for primary biliary cirrhosis. Anti-nuclear antibodies (ANA) also play an important role in mediating the immune response of primary biliary cirrhosis. Indirect immunofluorescence shows that anti-nuclear antibodies (ANA) are distributed on the nuclear membrane in two ways: multiple nuclear dots (MND) or nuclear membrane distribution (rim-like or membranous pattern).

Sp100 belongs to the multipoint distribution type, while gp210 and Nup62 belong to the nuclear envelope type. Sp100 is the main antigen of nuclear membrane multi-point distribution type antinuclear antibodies. It is a nuclear protein with a molecular weight of 54kDa and has transcription enhancing activity. Interferon can enhance the expression of Sp100.

The specificity of anti-gp210 antibody for primary biliary cirrhosis is close to 100%. Compared with M2 antibody, the presence of gp210 antibody is related to the prognosis of the disease and is considered to be related to the development of end-stage liver disease. The epitope of gp210 protein is located in the cytoplasmic part of the protein. Nup62 is a protein with a molecular weight of 55kDa, located on the central plug in the nuclear pore complex, and regulates the entry of proteins with nuclear localization signals into the nucleus. New data prove that anti-Nup62 antibodies are more frequent than anti-gp210 glycoprotein autoantibodies in patients with primary biliary cirrhosis.

1. Autoantibodies in polymyositis/dermatomyositis

Inflammatory myopathy is a disease with complex and diverse symptoms, which is mainly characterized by inflammatory infiltration of skeletal muscle. Common subtypes of this myopathy include adult polymyositis, dermatomyositis, body myositis, childhood myositis, and tumor-related myositis. In addition, inflammatory myopathy can overlap with other autoimmune connective tissue diseases. Data show that 8 of the 20 aminoacyl tRNA synthetases have been identified as targets for autoantibodies. These antibodies can be found in the serum of 30% of myositis patients and have high specificity for detecting these diseases. Its existence is also related to complex lung diseases. Anti-SRP autoantibodies are often present in necrotizing myopathy, accompanied by heart involvement. The appearance of this antibody indicates a severely poor prognosis and a poor response to treatment. Anti-Mi-2 autoantibody is a specific serological marker of dermatomyositis. It can be detected in the serum of 20% of myositis patients. It is a marker of acute onset, with a good prognosis and good treatment effect. Anti-PM/Scl (mainly PM/Scl 100) autoantibodies appear in patients with polymyositis, scleroderma or polymyositis/scleroderma overlap syndrome. The presence of PM/Scl 100 autoantibodies has a good prognosis for patients with polymyositis/scleroderma overlap syndrome. The difference is that when PM/Scl 100 and other myositis or systemic scleroderma-specific autoantibodies co-exist, it points to a poor prognosis. At present, many articles have described many autoantibodies in patients with inflammatory myopathy, especially those in patients with dermatomyositis. Studies have found that anti-p155/140 (TIF1 gamma) autoantibodies appear in more than 20% of patients with dermatomyopathies. And in patients with myopathy closely related to cancer, anti-TIF1 gamma is positive. MDA5 is a cytoplasmic protein with a molecular weight of 140kDa, and its autoantibodies are mainly found in Asian dermatomyositis patients. The appearance of this autoantibody is often associated with interstitial lung disease.

2. Recombinant SmD1 and SmD3 proteins for detecting autoantibodies

Systemic Lupus Erythematosus (SLE) is a chronic and inflammatory autoimmune connective tissue disease that can affect other parts of the body. Anti-Sm antibody is a highly specific antibody for systemic lupus erythematosus, which has been recorded in the classification standards of the American College of Rheumatology. Anti-Sm antibodies appear in 5-30% of SLE patients, this difference depends on the detection system and the criteria selected for cohort studies. The study also pointed out that there are ethnic differences in the incidence of anti-Sm antibodies. The Sm antigen is part of the splicing complex and catalyzes the splicing of nuclear precursor mRNA. Each spliceosome snRNP contains snRNAs (U1, U2, U4/U6 and U5), a unique connexin group, and a shared protein consisting of seven different Sm (SmB/SmB, SmD1, SmD2, SmD3, SmE, SmF and SmG), the molecular weight is between 9 and 29.5 kDa respectively. SmB and SmD polypeptides are the most common targets of anti-Sm-specific autoimmune responses, and SmD is regarded as the main Sm antigen.

SmD1, SmD3 and SmB/B proteins are methylated by arginine methyltransferase 5 (PRMT5; typical methyltransferase type II). The symmetric dimethylation of arginine residues catalyzed by PRMT5 in Sm protein should be very important for regulating snRNP aggregation.

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