دورية أكاديمية
أعرض في EDS

The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon.

التفاصيل البيبلوغرافية
العنوان: The role of DNA in the pathogenesis of SLE: DNA as a molecular chameleon.
المؤلفون: Pisetsky DS; Duke University Medical Center, Durham, North Carolina, USA david.pisetsky@duke.edu.; Medical Research, Durham VA Health Care System, Durham, North Carolina, USA., Herbert A; InsideOutBio Inc, Charlestown, Massachusetts, USA.
المصدر: Annals of the rheumatic diseases [Ann Rheum Dis] 2024 Jun 12; Vol. 83 (7), pp. 830-837. Date of Electronic Publication: 2024 Jun 12.
نوع المنشور: Journal Article; Review
اللغة: English
بيانات الدورية: Publisher: BMJ Country of Publication: England NLM ID: 0372355 Publication Model: Electronic Cited Medium: Internet ISSN: 1468-2060 (Electronic) Linking ISSN: 00034967 NLM ISO Abbreviation: Ann Rheum Dis Subsets: MEDLINE
أسماء مطبوعة: Publication: London : BMJ
Original Publication: London : H.K. Lewis
مواضيع طبية MeSH: Lupus Erythematosus, Systemic*/immunology , Lupus Erythematosus, Systemic*/genetics , Antibodies, Antinuclear*/immunology , DNA, Z-Form*/immunology , DNA, Z-Form*/genetics, Humans ; DNA/immunology ; DNA/genetics ; Animals ; DNA, B-Form/immunology ; DNA, B-Form/genetics
مستخلص: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterised by antibodies to DNA (anti-DNA) and other nuclear macromolecules. Anti-DNA antibodies are markers for classification and disease activity and promote pathogenesis by forming immune complexes that deposit in the tissue or stimulate cytokine production. Studies on the antibody response to DNA have focused primarily on a conformation of DNA known as B-DNA, the classic right-handed double helix. Among other conformations of DNA, Z-DNA is a left-handed helix with a zig-zag backbone; hence, the term Z-DNA. Z-DNA formation is favoured by certain base sequences, with the energetically unfavourable flip from B-DNA to Z-DNA dependent on conditions. Z-DNA differs from B-DNA in its immunogenicity in animal models. Furthermore, anti-Z-DNA antibodies, but not anti-B-DNA antibodies, can be present in otherwise healthy individuals. In SLE, antibodies to Z-DNA can occur in association with antibodies to B-DNA as a cross-reactive response, rising and falling together. While formed transiently in chromosomal DNA, Z-DNA is stably present in bacterial biofilms; biofilms can provide protection against antibiotics and other challenges including elements of host defence. The high GC content of certain bacterial DNA also favours Z-DNA formation as do DNA-binding proteins of bacterial or host origin. Together, these findings suggest that sources of Z-DNA can enhance the immunogenicity of DNA and, in SLE, stimulate the production of cross-reactive antibodies that bind both B-DNA and Z-DNA. As such, DNA can act as a molecular chameleon that, when stabilised in the Z-DNA conformation, can drive autoimmunity.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)
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معلومات مُعتمدة: I01 BX003772 United States BX BLRD VA; R01 AR073935 United States AR NIAMS NIH HHS
فهرسة مساهمة: Keywords: Autoantibodies; Autoimmunity; Lupus Erythematosus, Systemic
المشرفين على المادة: 0 (Antibodies, Antinuclear)
0 (DNA, Z-Form)
9007-49-2 (DNA)
0 (DNA, B-Form)
تواريخ الأحداث: Date Created: 20240515 Date Completed: 20240612 Latest Revision: 20240614
رمز التحديث: 20240614
مُعرف محوري في PubMed: PMC11168871
DOI: 10.1136/ard-2023-225266
PMID: 38749573
قاعدة البيانات: MEDLINE
الوصف
تدمد:1468-2060
DOI:10.1136/ard-2023-225266