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The HLA-Cw*06 allele may predict the response to methotrexate (MTX) treatment in Chinese arthritis-free psoriasis patients

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Abstract

MTX in genetically distinctive Chinese psoriatic patients remains less explored. The present study aimed to determine the impact of HLA-Cw*06 on MTX response in a Chinese psoriasis patient population. A total of 204 patients with psoriasis were enrolled in this study. Clinical data and DNA samples from all patients were collected. The allele of HLA-Cw*06 genotyping was detected using direct Sanger sequencing. This study enrolled 204 patients with psoriasis, including 47 (23.04%) psoriatic arthritis patients, 157 (76.96%) patients free of psoriatic arthritis. Overall, 110 (53.92%) of all patients carried the HLA-Cw*06 allele. This frequency in patients with arthritis-free psoriasis was higher than that in those with psoriatic arthritis (58.59 vs. 38.30%, P = 0.014). After 8 weeks of MTX treatment, the arthritis-free psoriasis patients, who tested positive for the HLA-Cw*06 allele, showed significant improvement compared to those who tested negative (For PASI50, 78.57 vs. 55.22%, P = 0.02, and for PASI75, 51.11 vs. 34.33%, P = 0.036). The psoriatic arthritis-free patients who carried the HLA-Cw*06 allele in combination with the ABCB1 rs1045642 CC genotype showed the highest improvement. A regression model containing HLA-Cw*06, rs1045642T > C, and initial PASI scores was used to construct the efficacy prediction model of MTX, which yielded AUC values of 73.2 and 75.6% for PASI50 and PASI75 to MTX, respectively, in arthritis-free psoriasis patients. The HLA-Cw*06 allele is associated with optimal response to MTX treatment in arthritis-free Chinese psoriasis patients. When combined with clinical indicators, the polymorphism explained more than 75% of the individual efficacy differences.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This work is supported by Grants from National Natural Science Foundation of China (81974479, 81773329, 82073447), National Key Research Grant (2018YFC0117004). We sincerely thank the participating patients and the volunteers for their generous and enthusiastic support for this study. We are also very grateful to Huashan Hospital of Fudan University for providing some of the samples.

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Contributions

MM, WZ, WC and XC: contributed to the study design, analysis, and manuscript writing, and MM contributed to data preparation. YK, WZ, MC, CL and KY: contributed to the clinical interpretation of the study findings. MM and PL: proposed statistical analysis methods and undertook the analysis. YL and CL: were responsible for verifying the underlying data. WZ and XC: secured the funding for the study. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication.

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Correspondence to Wu Zhu or Wangqing Chen.

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The authors have no conflict of interest to declare.

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This study was then assigned the registration number ChiCTR-OCH-14004518 in the Chinese Clinical Trial Registry.

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Mao, M., Kuang, Y., Chen, M. et al. The HLA-Cw*06 allele may predict the response to methotrexate (MTX) treatment in Chinese arthritis-free psoriasis patients. Arch Dermatol Res 315, 1241–1247 (2023). https://doi.org/10.1007/s00403-022-02498-x

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