Plasma Interleukin-6 Levels Correlate with Factor VIII Inhibitor Titers But Not Plasmablast Frequencies in Severe Hemophilia A Patients: A Case-Control Study.
- 1Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
- 2Department of Parasitology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
- 3Department of Pathology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
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.
Related
- 1010 HLA-B allele frequencies in immune checkpoint inhibitor-associated rheumatologic adverse events
- PO131 | BEYOND THE INHIBITOR TITER: THE IMPORTANCE OF EARLY COMBINED IMMUNOSUPPRESSIVE THERAPY IN THE MANAGEMENT OF ACQUIRED HEMOPHILIA A
- RECOMBINANT FACTOR VIII, FAMILY HISTORY, AND HIGH-TITER INHIBITOR RISK IN SEVERE HEMOPHILIA A
- PO127 | ANAPHYLACTIC REACTION TO RECOMBINANT ACTIVATED FVII IN A MILD HEMOPHILIA A PATIENT WITH INHIBITOR: A CASE REPORT
- PO024 | IMPLEMENTATION OF 4PL SIGMOIDAL REGRESSION FOR FACTOR VIII INHIBITOR QUANTIFICATION IN ACQUIRED HEMOPHILIA
BibTeX
@article{zarei2026plasma,
title = {{Plasma Interleukin-6 Levels Correlate with Factor VIII Inhibitor Titers But Not Plasmablast Frequencies in Severe Hemophilia A Patients: A Case-Control Study.}},
author = {Tahereh Zarei and Omid Reza Zekavat and Aref Teimouri and Amin Shahsavani and Helmi Helmi and Hossein Golmoghaddam and Shirin Parand and Nargess Arandi},
journal = {Iranian journal of medical sciences},
year = {2026},
month = oct,
doi = {10.30476/ijms.2026.110554.4625},
url = {https://europepmc.org/article/MED/42999772},
note = {CC BY-ND},
}
RIS
TY - JOUR
TI - Plasma Interleukin-6 Levels Correlate with Factor VIII Inhibitor Titers But Not Plasmablast Frequencies in Severe Hemophilia A Patients: A Case-Control Study.
AU - Tahereh Zarei
AU - Omid Reza Zekavat
AU - Aref Teimouri
AU - Amin Shahsavani
AU - Helmi Helmi
AU - Hossein Golmoghaddam
AU - Shirin Parand
AU - Nargess Arandi
PY - 2026
DA - 2026/10/01
JO - Iranian journal of medical sciences
DO - 10.30476/ijms.2026.110554.4625
UR - https://europepmc.org/article/MED/42999772
AB - 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.
SN - 0253-0716
SN - 1735-3688
ER -