IMMUNE DYSREGULATION IN RECURRENT DENGUE HEMORRHAGIC FEVER CASES

Abstract

Recurrent dengue hemorrhagic fever (DHF) presents a significant clinical challenge, with disease severity often driven by immune system dysregulation rather than viral load alone. This study aimed to investigate immunological alterations in patients with recurrent DHF and identify patterns associated with clinical severity. A total of 120 patients with at least two prior episodes of DHF were enrolled across three tertiary care hospitals in endemic regions. In the acute phase, analysis of peripheral blood included studying Alanine aminotransferase (ALT), complement activation, specific T cell subsets and the release of cytokines.  Around 40% of patients had Grade II illness and 30% had Grade III and the study indicated that DENV-2 and DENV-3 were involved the most in patients’ recurring symptoms.  As the problem worsened, the levels of IL-6, IL-10, TNF-α and IFN-γ were observed to gradually climb.  Intriguingly, the correlation between IL-6 and TNF-α was very high (r = 0.78) which connects them in causing the cytokine storm related to DHF.  High complement component C5b-9 was found in severe patients, indicating that complement activation is responsible for a larger amount of plasma leakage.  The higher number of CD8+ T cells and lower activity of regulatory T cells in the blood of severe patients indicated that the immune system was not well-controlled.  Serotype-specific studies show that infections with DENV-2 stimulated the most significant inflammatory and complement reactions among the viruses.  Overall, the findings point out that the severity of DHF is due to hyperactivation of the complement system, a lack of properly balanced cytokines and weak immune control.  Results suggest that both C5b-9 and IL-6 can guide new treatments in immunology and point to the development of diseases.  If high-risk individuals are identified using immunological profiling, new treatments and vaccines for dengue could help protect them and further improve their outcomes.