Low C4A copy numbers and higher HERV gene insertion contributes to increased risk of SLE, with absence of association with disease phenotype and disease activity.
Complement C4 gene
Copy number variations
Droplet digital PCR
Human endogenous retrovirus-K
Systemic lupus erythematosus
Journal
Immunologic research
ISSN: 1559-0755
Titre abrégé: Immunol Res
Pays: United States
ID NLM: 8611087
Informations de publication
Date de publication:
10 Apr 2024
10 Apr 2024
Historique:
received:
18
01
2024
accepted:
23
03
2024
medline:
10
4
2024
pubmed:
10
4
2024
entrez:
9
4
2024
Statut:
aheadofprint
Résumé
Low copy numbers (CNs) of C4 genes are associated with systemic autoimmune disorders and affects autoantibody diversity and disease subgroups. The primary objective of this study was to characterize diversity of complement (C4) and C4-Human Endogenous Retrovirus (HERV) gene copy numbers in SLE. We also sought to assess the association of C4 and C4-HERV CNs with serum complement levels, autoantibodies, disease phenotypes and activity. Finally, we checked the association of C4 and HERV CNs with specific HLA alleles. Genomic DNA from 70 SLE and 90 healthy controls of south Indian Tamil origin were included. Demographic, clinical and serological data was collected in a predetermined proforma. CNs of C4A and C4B genes and the frequency of insertion of 6.4kb HERV within C4 gene (C4AL, C4BL) was determined using droplet digital polymerase chain reaction (ddPCR). A four digit high resolution HLA genotyping was done using next generation sequencing. In our cohort, the total C4 gene copies ranged from 2 to 6. Compared to controls, presence of two or less copies of C4A gene was associated with SLE risk (p = 0.005; OR = 2.79; 95% CI = 1.29-6.22). Higher frequency of HERV insertion in C4A than in C4B increases such risk (p = 0.000; OR = 12.67; 95% CI = 2.80-115.3). AL-AL-AL-BS genotype was significantly higher in controls than SLE (9%vs1%, p = 0.04; OR = 0.15, 95% CI = 0.00-0.16). Distribution of HLA alleles was not different in SLE compared to controls as well as in SLE subjects with ≤ 2 copies and > 2 copies of C4A, but HLA allele distribution was diverse in subjects with C4B ≤ 2 copies and > 2 copies. Finally, there was no correlation between the C4 and the C4-HERV diversity and complement levels, autoantibodies, disease phenotypes and activity. In conclusion, our data show that, low C4A copy number and higher insertion of HERV-K in C4A increases the risk for SLE. C4 and C4-HERV CNs did not correlate with serum complements, autoantibodies, disease phenotypes and activity in SLE. Further validation in a larger homogenous SLE cohort is needed.
Identifiants
pubmed: 38594415
doi: 10.1007/s12026-024-09475-8
pii: 10.1007/s12026-024-09475-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : IFCPAR/CEFIPRA-5103-1-Negi/Tamouza
ID : 5103-1
Organisme : IFCPAR/CEFIPRA-5103-1-Negi/Tamouza
ID : 5103-1
Organisme : IFCPAR/CEFIPRA-5103-1-Negi/Tamouza
ID : 5103-1
Organisme : IFCPAR/CEFIPRA-5103-1-Negi/Tamouza
ID : 5103-1
Organisme : IFCPAR/CEFIPRA-5103-1-Negi/Tamouza
ID : 5103-1
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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