IL-6 Autoantibodies Predict Lower Platelet Counts and Altered Plasma Cytokine Profiles in Healthy Blood Donors: Results From the Danish Blood Donor Study

Frontiers in Medicine

article

Jakob Hjorth von Stemann¹  Ole Birger Vesterager Pedersen²  Henrik Hjalgrim³  Christian Erikstrup⁷  Henrik Ullum⁸  Joseph Dowsett¹  Lise Wegner Thørner¹  Margit Anita Hørup Larsen¹  Erik Sørensen¹  Morten Bagge Hansen¹  Sisse Rye Ostrowski¹ 

[1] Department of Clinical Immunology, Rigshospitalet, Copenhagen University Hospital;Department of Clinical Immunology, Zealand University Hospital;Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen;Department of Epidemiology Research, Statens Serum Institut;Centre for Cancer Research, Danish Cancer Society;Department of Haematology, Rigshospitalet, Copenhagen University Hospital;Department of Clinical Immunology, Aarhus University Hospital;Statens Serum Institute

关键词: autoimmunity;    IL-6;    platelets;    epidemiology;    blood donors;    cytokine autoantibodies;    cytokines;    thrombopoiesis;   

DOI  :  10.3389/fmed.2022.914262

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

Cytokine-specific autoantibodies (c-aAb) represent a novel type of immune dysfunction. Though they have been detected in both patient cohorts and healthy individuals, and have immunomodulatory properties, the full extent of their influence remains unknown. Based on the critical role of several cytokines in thrombopoiesis, we investigated if there is an association between c-aAb and platelet variables in healthy individuals, with a specific focus on c-aAb against a known thrombopoietic cytokine, IL-6. Using platelet count and mean platelet volume in 3,569 healthy participants of the Danish Blood Donor Study as dependent variables, we performed a series of multivariate regression analyses using five cytokine autoantibodies, including IL-6 c-aAb, as independent variables. In men, high titers of IL-6 c-aAb were negatively associated with platelet counts (β = −24 * 10 9 /l (95% confidence interval −43 to −6), p = 0.008) and positively associated with mean platelet volume (β = 0.4 fL (95% confidence interval 0.0–0.7) p = 0.043). These associations were exacerbated when adjusting for undetectable C-reactive protein levels, which we used as a proxy for c-aAb mediated IL-6 inhibition in vivo . Furthermore, in a smaller subgroup, individuals with high vs. low titer IL-6 c-aAb had different profiles of plasma IL-6, IL-10, TNFα and TPO, further suggesting a functional inhibition of IL-6 by high titers of circulating IL-6 c-aAb. We therefore speculate that in addition to their immunomodulatory potential IL-6 c-aAb may interfere with thrombopoiesis – directly or indirectly – under normal physiological conditions. This study is the first to suggest an influence of c-aAb on platelets in healthy individuals, beyond their apparent effects on immune competence.

【 授权许可】

CC BY