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High incidence of antinuclear antibodies that recognize the matrix attachment region
1Department of Medical Technology, Okayama University, Okayama, 700-8558, Japan.
Abstract:
The matrix attachment region (MAR) is a distinctive genomic DNA involved in a variety of nuclear processes through association with the nuclear matrix. Recent studies suggest that nuclear matrix is altered in the process of apoptosis and presented to the immune system, leading to the production of autoantibodies against its protein components. To see whether MARs are also recognized by autoantibodies, a collection of human sera containing antinuclear antibodies was screened for the presence of binding activities against cloned MARs. We found that MAR-binding activities are quite common in these sera. There was a positive correlation among the MAR-binding titers for three different MAR probes. As expected, the MAR-binding activity was copurified with serum IgG, and subclass analysis with affinity-purified IgG on MAR-Sepharose showed a predominance of IgG2 isotype. Several lines of evidence implied that the anti-MAR antibodies detected here is distinct from the ordinary anti-DNA antibodies that are reactive to bulk DNA.
Insights
Autoantibodies targeting matrix attachment regions (MARs) are common in human sera. These anti-MAR antibodies, primarily IgG2, are distinct from typical anti-DNA antibodies and may play a role in nuclear matrix autoimmunity.
Area of Science:
- Molecular Biology
- Immunology
- Genetics
Background:
- Matrix attachment regions (MARs) are DNA elements crucial for nuclear organization and processes.
- Alterations in the nuclear matrix during apoptosis can trigger autoimmune responses against its protein components.
Purpose of the Study:
- To investigate the presence and characteristics of autoantibodies targeting MARs in human sera.
- To determine if anti-MAR antibodies are distinct from antibodies against bulk DNA.
Main Methods:
- Screening of human sera with known antinuclear antibodies for binding activity against cloned MARs.
- Copurification of MAR-binding activity with serum IgG and subclass analysis.
- Distinguishing anti-MAR antibodies from anti-DNA antibodies.
Main Results:
- MAR-binding autoantibodies were frequently detected in the screened human sera.
- A positive correlation was observed between MAR-binding titers using different MAR probes.
- The identified anti-MAR antibodies were predominantly of the IgG2 isotype and distinct from antibodies reactive to bulk DNA.
Conclusions:
- Autoantibodies against MARs are common in individuals with antinuclear antibodies.
- These anti-MAR antibodies represent a distinct autoimmune response, separate from typical anti-DNA antibodies.
- The findings suggest a potential role for anti-MAR antibodies in autoimmune diseases involving the nuclear matrix.