Human autoantibodies to poly(adenosine diphosphate-ribose) polymerase

Area of Science:

• Biochemistry
• Immunology
• Molecular Biology

Background:

• Poly(ADP-ribose) polymerase (ADPRP) is a chromatin-bound enzyme crucial for DNA repair and replication.
• ADPRP activation is implicated in lymphocyte dysfunction and inflammatory diseases.
• Its role in inborn errors of nucleoside metabolism has also been suggested.

Purpose of the Study:

• To investigate the presence of autoantibodies against ADPRP in patients with rheumatic complaints.
• To characterize the specificity and reactivity of these potential anti-ADPRP autoantibodies.

Main Methods:

• Detection of IgG autoantibodies in patient sera using immunoprecipitation and immunoblotting techniques.
• Purification of ADPRP from human and calf thymus.
• Immunofluorescence assays using HEp-2 cells to determine antibody binding patterns.

Main Results:

• High titers of IgG autoantibodies specifically against ADPRP were detected in six patients with rheumatic complaints.
• No other autoantibodies were found in these sera.
• The autoantibodies recognized both native and digested forms of ADPRP from different species and exhibited a distinct nuclear and nucleolar immunofluorescence pattern.

Conclusions:

• This study describes, for the first time, autoantibodies to ADPRP.
• The findings suggest a potential link between DNA damage, immune response against ADPRP, immunodeficiency, and autoimmunity.
• Further research is warranted to explore the implications of anti-ADPRP autoimmunity in rheumatic diseases and related conditions.