Background: Helicobacter pylori ( HPY ) provokes gastrointestinal disorders and gastric cancer. We supposed that HPY disrupts the 25-OH-Vitamin-D3 (Vit.D3) absorption. We evaluated the association between Vit.D3 and anti- HPY immunoglobulins (Igs) and the Vit.D3 potency as a predictive biomarker for HPY infection. Materials and Methods: 603 patients’ raw data were gathered from a private clinical laboratory. Anti- HPY Igs including serum IgG, IgA, and IgM, in addition to HPY -stool antigen, were assessed by the immunoassay methods. Vit.D3 was determined by high-pressure liquid chromatography. Correlations, ordinal comparisons, cutoff points (COP), and odds ratio (OR) were estimated. Results: The age mean ± standard deviation was 39.83 ± 18.426 for female and 38.82 ± 16.937 for male participants ( P = 0.521). Significant correlations existed after age and gender adjustment between Vit.D3 serum levels and the HPY IgG ( R = 0.298) and IgA ( R = 0.271) but not for IgM ( R = −0.103). Approximately, 48% of males and 36% of females had insufficient/deficient Vit.D3 serum levels (male/female OR: 1.65; 1.16–2.33; P = 0.0051). After age and gender adjustment, the best COP of Vit.D3 to predict an HPY IgG-positive patient was Vit.D3 >32.80 ng/mL with 66.23% diagnostic accuracy (DAAC), 30.43% specificity (SPC), and 90.41% sensitivity (SEN). For the HPY IgA, the values were Vit.D3 >37.83 ng/mL, DAAC = 60.45%, SPC = 58.82%, SEN = 64.20%. For HPY IgM, the values were Vit.D3 >37.32 ng/mL, DAAC = 58.97%, SPC = 57.33%, and SEN = 100%. Conclusions: Vit.D3 had a good association with anti- HPY Igs and may be a good biomarker for immunity competence against HPY infection if the patient's age and gender are considered when interpreting the laboratory results.
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