Role of IL-35, Vitamin B12, and Folate Deficiency in Patients with Megaloblastic Anemia

(1) Background: Megaloblastic anemia is described as a reduction in red blood cell (RBC) count. Caused by deficits in vital cofactors of folate and vitamin B12 for the synthesis of deoxyribonucleic acid (DNA). The heterodimeric inhibitory cytokine interleukin-35 (IL-35) serves as a biomarker of immune-mediated involvement in anemia. This study was designed to investigate IL-35 levels in patients with megaloblastic anemia and to examine their correlation with hematological parameters. (2) Methods: A total of 180 participants (80 megaloblastic anemia patients and 100 healthy participants), aged between 18 and 65 years, were enrolled. For all participants, clinical laboratory testing, including complete blood count (CBC), peripheral blood smear, serum vitamin B12, folate levels, and IL-35 analysis, was performed. (3) Results: There was a significant difference in the development of megaloblastic anemia with age. Patients showed an elevated mean of mean corpuscular volume (MCV) value (93.43), indicating macrocytosis. Elliptocyte, hypersegmented neutrophils, anisopoikilocyte, and dacrocyte were shown in a blood smear. Vitamin B12 levels were significantly lower in patients compared to the control group (p < 0.0001), and folate levels showed no significant difference (p = 0.914). All patients had a lower level of IL-35, despite no association with any particular hematological parameter. (4) Conclusions: The primary cause of megaloblastic anemia is vitamin B12 deficiency, which leads to macrocytosis and presents abnormal cells in the blood smear. The IL-35 low levels are detectable for inflammation that is present in the bone marrow microenvironment and used as a biomarker in this type of anemia.