Study on the Correlation Between IgG Subtype of Anti-dsDNA Antibody and SLE

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease of unclear pathogenesis, characterized by the production of multiple autoantibodies and involving multiple organs and systems. The course of SLE can be divided into an active disease phase and a remission phase. The clinical manifestations of SLE patients in different disease states vary greatly. Most patients in the active phase have severe clinical symptoms that can easily cause damage to major organs. Treatment of SLE is therefore mainly aimed at achieving remission or a state of reduced disease activity.

The main features of SLE are the production of multiple autoantibodies in the blood and damage to multiple organs and systems. Not only does SLE manifest clinically as multi-organ and multi-system involvement, such as the kidneys, blood, musculoskeletal and circulatory systems, but it also has great heterogeneity in autoantibody levels. Under the action of multiple autoantibodies, SLE patients will have different clinical manifestations, ranging from relatively mild clinical manifestations such as rash or arthritis to severe life-threatening clinical manifestations such as lupus crisis and renal artery embolism. This heterogeneity of clinical manifestations also leads to different treatment responses and prognoses in patients. In addition, SLE patients still suffer from many complications, the most common of which is lupus nephritis (LN), which is also one of the leading causes of death in SLE patients. It is therefore very important to monitor organ damage in SLE patients.

Diagnostic study of anti-double-stranded DNA antibodies in SLE

The literature reports that IgG anti-double-stranded DNA antibodies are associated with disease activity and organ involvement in SLE patients. At the same time, studies have shown that IgG anti-double-stranded DNA antibodies are more sensitive in diagnosing SLE (sensitivity 83%), while IgA anti-double-stranded DNA antibodies are more specific (specificity 42%); however, IgG anti-double-stranded DNA antibodies are currently the main test in clinical practice. In addition, studies have shown that combined detection of IgA and IgG anti-double-stranded DNA antibodies can help identify active lesions of glomerulonephritis in LN patients, while IgM anti-double-stranded DNA antibodies may be a protective factor for patients with SLE. In addition, anti-double-stranded DNA antibodies are not unique to SLE patients and are often seen in severe infections and malignancies, but their production mechanisms may be different. At the same time, there are five subtypes of anti-double-stranded DNA antibodies produced in mammals, two of which (bacterial double-stranded DNA antibodies and viral double-stranded DNA antibodies) are related to infection, and the production of two cross-reactive subtypes (kidney-related and non-kidney-related subtypes) is related to the effects of kidney and non-kidney proteins/phospholipids. It can be seen that different subtypes of anti-double-stranded DNA antibodies have different production mechanisms and different functions. The pathogenicity of anti-double-stranded DNA antibodies has been demonstrated in autoimmune diseases.

Since the early 1960s, the IgG subtypes of antibodies have been identified. Currently, four IgG subtypes have been found to exist, namely IgG1, IgG2, IgG3, and IgG4. In addition, different IgG subtypes of antibodies have different functions. Among different IgG subtypes, IgG2 subtype can activate complement more effectively than IgG1 and IgG3 subtypes, while IgG4 subtype antibodies hardly activate complement. Therefore, the distribution of different IgG subtypes of autoantibodies may be different in autoimmune diseases, and this difference in different IgG subtypes of autoantibodies may be related to the complex pathogenesis of SLE. According to literature reports, about 65%-70% of IgG subtypes in the blood circulation of healthy people belong to the IgG1 subtype, IgG2 subtype accounts for about 20-25% of the total IgG in the circulation, and IgG3 and IgG4 each account for less than 10%. At the same time, studies have found that the distribution of different IgG subtypes of different anti-double-stranded DNA antibodies in lupus nephritis is quite different. Using a large sample size study, researchers found that IgG2 antinuclear antibodies have a special pathophysiological role in LN patients. In LN patients, IgG2 autoantibodies are the most abundant subtypes in their circulation, and the level of IgG2 anti-double-stranded DNA antibodies is higher in SLE and LN patients than in healthy people, but the level of IgG2 anti-double-stranded DNA antibodies was not different between SLE patients with LN and non-LN. Another study found that the frequency of IgG2, IgG3 anti-nuclear histone antibodies and IgG2 anti-double-stranded DNA antibodies in SLE patients with renal involvement was higher than that in SLE patients with extrarenal manifestations. It can be seen that different IgG subtypes of anti-double-stranded DNA antibodies may have different relationships with different clinical phenotypes of SLE patients. In clinical practice, the detection of autoantibodies has many advantages over other forms of molecular diagnostic methods, such as low cost, convenience, and non-invasiveness. Therefore, enzyme-linked immunosorbent assay (ELISA) is often used to detect anti-double-stranded DNA antibodies of different IgG subtypes.

dsDNA Antibody

dsDNA Antigens

dsDNA ELISA