Podoconiosis is a geo-chemically induced, non-infectious, familial, chronic lymphedema of the legs that occurs among barefoot people in rural, farming communities with extreme poverty. Despite a growing body of research surrounding the disease, the pathogenesis of the disease is relatively unknown. This study aims to investigate the immunological and hematological profiles of individuals affected by podoconiosis in comparison to healthy controls. A comparative cross-sectional study was conducted in West Gojjam Zone of Ethiopia involving adult individuals clinically diagnosed with podoconiosis (n = 53) and healthy controls (n = 67) from the same area. A survey was conducted to gather information on sociodemographic, lifestyle characteristics, and clinical features of the disease. About nine ml whole blood samples were collected for hematological and immunological testing, which included IL-4, TNF-α, IL-6, IL-17, IL-10, TGF β and IFN-γ. Overall, we observed significant differences in hematological parameters between individuals with podoconiosis and healthy controls. Specifically, we found a notable reduction in white blood cell count, with an adjusted mean difference (AMD) of -1.15 (95% CI: -2.09 to -0.21; p = 0.017). Additionally, the differential white blood count showed a decrease in absolute neutrophils (AMD = -3.42, 95% CI: -4.15 to -2.69; p < 0.001) and absolute eosinophils (AMD = -0.20, 95% CI: -0.37 to -0.03; p = 0.019). Conversely, we noted an increase in absolute lymphocytes (AMD = 0.98, 95% CI: 0.50 to 1.46; p < 0.001) and monocytes (AMD = 0.54, 95% CI: 0.22 to 0.85; p = 0.001). However, we didn't observe a significant difference in cytokine profile between podoconiosis patients and healthy controls. The decrease in neutrophil counts among podoconiosis cases compared to healthy controls may provide insight into the potential disease pathogenesis, suggesting the involvement of autoimmune-related mechanisms, as it demonstrates a similar hematological profile to other autoimmune disorders.
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