Contribution of Impaired DNASE1L3 Activity to Anti-DNA Autoantibody Production in Systemic Lupus Erythematosus

Overview

Journal Rheumatol Immunol Res

Specialty Allergy & Immunology

Date 2022 Dec 5

PMID 36467024

Authors

Samarth Mathapathi

Cong-Qiu Chu

Affiliations

Soon will be listed here.

Abstract

Anti-DNA autoantibodies are pathogenic in systemic lupus erythematosus (SLE). Cell-free chromatin associated long DNA fragments are antigens for anti-DNA antibodies. In health state, released by cell death and actively secreted by live cells, these cell-free DNA are cleared by deoxyribonucleases (DNASES). In SLE, cell-free DNA are accumulated. The defective clearance of long fragments of cell-free DNA in SLE is largely attributed to impaired deoxyribonuclease 1 like 3 (DNASE1L3). null mutation results in monogenic SLE. The SLE risk single-nucleotide polymorphism (rs35677470) encodes R260C variant DNASE1L3, which is defective in secretion, leading to reduced levels of DNASE1L3. In addition, neutralizing autoantibodies to DNASE1L3 are produced in SLE to inhibit its enzymatic activity.

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