Plasma Interleukin-6 Levels Correlate with Factor VIII Inhibitor Titers But Not Plasmablast Frequencies in Severe Hemophilia A Patients: A Case-Control Study.

Authors

Tahereh Zarei, Omid Reza Zekavat, Aref Teimouri, Amin Shahsavani, Helmi Helmi, Hossein Golmoghaddam, Shirin Parand, Nargess Arandi

Published in

Iranian journal of medical sciences. Volume 51. Issue 10. Pages 712-719. Epub Oct 01, 2026.

Abstract

Inflammatory cytokines are thought to contribute to the development of inhibitors against factor VIII (FVIII) in patients with severe hemophilia A (HA). In this study, we evaluated the association between plasma interleukin-6 (IL-6) levels and inhibitor development and plasmablast frequencies in severe HA patients.
This case-control study included 32 severe HA patients, who were admitted to the Comprehensive Hemophilia Center affiliated with Shiraz University of Medical Sciences between January and December 2022. The studied groups comprised eight severe HA patients with inhibitors, 24 without inhibitors, and 24 age- and sex-matched healthy controls. Plasma IL-6 levels were measured using the enzyme-linked immunosorbent assay (ELISA) and compared between studied groups using the Student's t test (for two groups) and ANOVA (for more than 2 groups). Correlation between IL-6 levels and inhibitor titers, as well as plasmablast frequencies, was assessed using Spearman's correlation test.
Plasma IL-6 levels were higher in HA patients than healthy controls; however, the difference was not statistically significant (P=0.197). Patients with inhibitors exhibited significantly elevated IL-6 levels compared with both inhibitor-negative HA patients (*P=0.001) and healthy controls (*P=0.001). Moreover, plasma IL-6 levels correlated significantly with inhibitor titers (r=0.393, *P=0.026) but not plasmablast frequencies (r=0.173, P=0.208). Receiver operating characteristic (ROC) curve analysis indicated that elevated IL-6 is a specific but moderately sensitive marker for inhibitor status in severe HA patients (sensitivity=62.5%, and specificity=87.5%, *P=0.027).
This study suggests that plasma IL-6 levels may serve as a fair-to-good immunological marker for predicting inhibitor development in severe HA patients.

PMID:
42999772
Bibliographic data and abstract were imported from PubMed on 08 Nov 2026.

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