Objective Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease. Genetic factors may play a pivotal role in determining susceptibility to these disorders. HLA associations with SSc, especially HLA class II, were investigated in different populations but not in Tunisia. Our aim was to study HLA profile in South Tunisian patients with SSc. Methods We conducted a case–control study on 19 SSc patients and 123 healthy controls. HLA class I (HLA-A and -B) typing was performed using a microlymphocytotoxicity complement–dependent technique followed by polymerase chain reaction sequence specific primer (PCR-SSP). HLA class II DRB1/DQB1 of all patients and controls was genotyped using the PCR-SSP technique. Statistical analysis was performed using SPSS software and R language. Results Nineteen SSc patients and 123 healthy controls were included. The HLA-DRB111 was associated with the genetic susceptibility to SSc (corrected p-value (pc) = 0.005; OR = 5.56; 95% CI = [2–15.4]). The HLA-DQB103:01 had also increased the risk of SSc in our study (pc = 0.002; OR = 5.9; 95% CI = [2–16.8]). Concerning HLA class I typing, we found a significant association between HLA-B53 and SSc (pc = 0.01; OR = 9; 95% CI = [2.53–31.99]). The association of HLA-B53 was independent of HLA-DRB111 in binary logistic regression test (HLA-B53: p = 0.01; HLA-DRB111: p = 0.008). Concerning the haplotype study, a significant difference in the distribution of the haplotype B53-DRB111 was found between patients and controls (13.15% in SSc patients vs. 0.8% in controls; p = 1.33 10−5; HaploScore = 4.35). Conclusion Our results showed that in South Tunisia SSc is associated with HLA-DRB111 and DQB103:01 alleles. A susceptibility to SSc was found in positive HLA-B53 patients. This association of HLA alleles with SSc needs further study. <Table Float="No" ID="Taba"> <tgroup cols="2"> <colspec align="left" colname="c1" colnum="1" /> <colspec align="left" colname="c2" colnum="2" /> <tbody> <row> <entry align="left" nameend="c2" namest="c1"> Key Points •HLA-DR and DQ alleles represent the most common associations reported in Systemic Sclerosis (SSc). •In this study, in addition to the known association with HLA-DRB111, we identified an association with HLA-B53 in a cohort of 19 South Tunisian patients. </entry> </row> </tbody> </tgroup> </Table>

HLA polymorphisms in South Tunisian systemic sclerosis patients: a case-control study

期刊论文
发表日期：

2025年9月10日

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Aida Charfi,
Raida Ben Salah,
Olfa Frikha,
Nadia Mahfoudh,
Arwa Kamoun,
Yosra Bouattour,
Lilia Gaddour,
Feiza Hakim,
Zouhir Bahloul,
Hafedh Makni

摘要

Objective

Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease. Genetic factors may play a pivotal role in determining susceptibility to these disorders. HLA associations with SSc, especially HLA class II, were investigated in different populations but not in Tunisia. Our aim was to study HLA profile in South Tunisian patients with SSc.

Methods

We conducted a case–control study on 19 SSc patients and 123 healthy controls. HLA class I (HLA-A and -B) typing was performed using a microlymphocytotoxicity complement–dependent technique followed by polymerase chain reaction sequence specific primer (PCR-SSP). HLA class II DRB1/DQB1 of all patients and controls was genotyped using the PCR-SSP technique. Statistical analysis was performed using SPSS software and R language.

Results

Nineteen SSc patients and 123 healthy controls were included. The HLA-DRB1*11 was associated with the genetic susceptibility to SSc (corrected p-value (pc) = 0.005; OR = 5.56; 95% CI = [2–15.4]). The HLA-DQB1*03:01 had also increased the risk of SSc in our study (pc = 0.002; OR = 5.9; 95% CI = [2–16.8]). Concerning HLA class I typing, we found a significant association between HLA-B53 and SSc (pc = 0.01; OR = 9; 95% CI = [2.53–31.99]). The association of HLA-B53 was independent of HLA-DRB1*11 in binary logistic regression test (HLA-B53: p = 0.01; HLA-DRB1*11: p = 0.008). Concerning the haplotype study, a significant difference in the distribution of the haplotype B53-DRB1*11 was found between patients and controls (13.15% in SSc patients vs. 0.8% in controls; p = 1.33 10⁻⁵; HaploScore = 4.35).

Conclusion

Our results showed that in South Tunisia SSc is associated with HLA-DRB1*11 and DQB1*03:01 alleles. A susceptibility to SSc was found in positive HLA-B53 patients. This association of HLA alleles with SSc needs further study.

Key Points

•HLA-DR and DQ alleles represent the most common associations reported in Systemic Sclerosis (SSc).

•In this study, in addition to the known association with HLA-DRB1*11, we identified an association with HLA-B53 in a cohort of 19 South Tunisian patients.