Clinicogenomic factors of biotherapy immunogenicity in autoimmune disease: A prospective multicohort study of the ABIRISK consortium

自身免疫性疾病生物治疗免疫原性的临床基因组学因素:ABIRISK 联盟的一项前瞻性多队列研究

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作者:Signe Hässler, Delphine Bachelet, Julianne Duhaze, Natacha Szely, Aude Gleizes, Salima Hacein-Bey Abina, Orhan Aktas, Michael Auer, Jerôme Avouac, Mary Birchler, Yoram Bouhnik, Olivier Brocq, Dorothea Buck-Martin, Guillaume Cadiot, Franck Carbonnel, Yehuda Chowers, Manuel Comabella, Tobias Derfuss, 

Background

Biopharmaceutical products (BPs) are widely used to treat autoimmune diseases, but immunogenicity limits their efficacy for an important proportion of patients. Our knowledge of patient-related factors influencing the occurrence of antidrug antibodies (ADAs) is still limited.

Conclusion

In our study, we found that immunosuppressants and antibiotics were associated with decreased risk of ADA development, whereas tobacco smoking and infections during the study were associated with increased risk. We found that the HLA-DQA1*05 allele was associated with an increased rate of immunogenicity. Moreover, our results suggest a relationship between CXCL12 production and ADA development independent of the disease, which is consistent with its known function in affinity maturation of antibodies and plasma cell survival. Our findings may help physicians in the management of patients receiving biotherapies.

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