Background: The occurrence of inhibitory alloantibodies against FVIII is one of the most challenging complication of replacement therapy for haemophilia A (HA) patients. Despite the clinical relevance of FVIII inhibitors, the immune mechanisms that leads to the production of inhibitors are not clearly understood. This study is aimed to discover the relation between immune cytokines and inhibitors development amongst Malaysian patients with severe haemophilia A
Material and Methods: This study involves a total of 46 severe HA patients; 15 with inhibitors and 31 without inhibitors. Patient’s samples were obtained from the Haemophilia Clinic, National Blood Centre, Kuala Lumpur. Tissue Necrosis Factor alpha (TNFa) known as pro-inflammatory cytokine and regulatory cytokine Interleukin 10 (IL10) were selected for cytokines measurement. Enzyme-Linked Immunosorbent Assay (ELISA) method were used to measure the TNFa and IL-10 concentration in plasma sample.
Results: Fifteen patients with inhibitors showed TNFa level of 114.40pg/ml (IQR) while thirty one patients without inhibitors showed 134.90pg/ml (IQR). Patients with inhibitors titre <5 BU (73.3%) expressed 263.32pg/ml, an average level of TNFa while patients with inhibitors titre ≥5 BU (26.7%) expressed an 177.58pg/ml. IL10 level for patients with inhibitors and without inhibitors were of 203.90pg/ml (IQR) and 37.10pg/ml (IQR) respectively. An average level of IL10 in patients with patients with inhibitor titre <5 BU and inhibitor titre ≥5 BU were of 125.41pg/ml and 414.65pg/ml respectively.
Discussion and Conclusion: This preliminary study shows a significance difference (p value <0.053) of plasma TNFa concentration which was higher among patients with inhibitors titre <5 BU as compared to patients with inhibitors titre ≥5 BU. In contrast, patients with inhibitors titre <5 BU showed a lower level of IL10 as compared to patients with inhibitors titre ≥5 BU where this is also statistically significance (P value <0.058). Findings of the mixed pattern of cytokine profiles in severe haemophilia A patients seemed to be associated with the presence of FVIII inhibitors which requires further verification with a larger sample size of study.
Keywords: Haemophilia A, inhibitors, cytokines