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10.04.2024 | Research

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

verfasst von: Christina Mary Mariaselvam, Gaurav Seth, Chengappa Kavadichanda, Wahid Boukouaci, Ching-Lien Wu, Bruno Costes, Molly Mary Thabah, Rajagopal Krishnamoorthy, Marion Leboyer, Vir Singh Negi, Ryad Tamouza

Erschienen in: Immunologic Research

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Abstract

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.

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Titel: 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
verfasst von: Christina Mary Mariaselvam
Gaurav Seth
Chengappa Kavadichanda
Wahid Boukouaci
Ching-Lien Wu
Bruno Costes
Molly Mary Thabah
Rajagopal Krishnamoorthy
Marion Leboyer
Vir Singh Negi
Ryad Tamouza
Publikationsdatum: 10.04.2024
Verlag: Springer US
Erschienen in: Immunologic Research
Print ISSN: 0257-277X
Elektronische ISSN: 1559-0755
DOI: https://doi.org/10.1007/s12026-024-09475-8

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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

Abstract

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Die Highlights vom Kongress des American College of Cardiology 2024

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