Evaluation of HLA-G and Hematobiochemical levels and their association with malaria and miscarriage among pregnant women: A Ghanaian case-control study

Background HLA-G (Human Leukocyte Antigen-G) is a non-classical molecule belonging to the major histocompatibility complex (MHC) class I family, located on chromosome 6 within the MHC region, which is pivotal in promoting immune tolerance. The immune-suppressive ability of Human Leukocyte Antigen (HLA-G) and its binding to fetal maternal interface predispose pregnant women to Plasmodium falciparum ( Pf ) infection and pregnancy loss, respectively. Alterations in hematological parameters may accelerate the severity of malaria infection. Limited data is available about the effects of malaria infection on hepatocytes and how this endangers the lives of the mother and the fetus due to liver injury. Thus, this study evaluated HLA-G and Hematobiochemical levels and their association with malaria infection and miscarriage among pregnant women in the Ghanaian population. Materials and Methods This case-control study recruited forty-six (46) Pf -infected pregnant women and forty-six (46) Pf -uninfected pregnant women from the Bibiani Anhwiaso Bekwai Municipality, Ghana. A well-structured questionnaire was administered to obtain sociodemographic and clinical data from 21 st December 2022–20 th December 2023. 10 ml venous blood samples were collected from each participant for Pf parasite testing using the Pf HRP2 RDT test kit (CareStart TM Malaria PfHRP2/pLDH Ag RDT, Access Bio, Inc., USA), and the results were confirmed with microscopy. Hematobiochemical profile analyses were done using the Sysmex automated hematology and chemistry analyser. Plasma HLA-G levels were quantified using a sandwich ELISA (Maxisop ELISA plate), and their corresponding concentrations were determined. Results The results shows a significant difference in the use of IPT-SP and Pf infection, with 31(67.4%) for Pf positive vs 18(39.1%) for Pf negative among those who were not on IPT-SP and 15(32.6%) for Pf positive vs 28(60.9%) for Pf negative for those who were on IPT-SP (p = 0.007)., Multivariate regression crude analysis shows increased ALT levels among the malaria-infected pregnant women [β = 7.091(95% CI = 1.563–32.182) p = 0.011] compared to the negative group. This finding was insignificant after adjusting for age, IPT-SP use and Trimester. ALP, on the other hand, shows significantly increased levels among the malaria-infected pregnant women compared to the malaria-negative pregnant women for both crude [β = 13.301(95% CI = 1.577–112.208) p = 0.017] and adjusted [β = 17.524(95% CI = 1.534–200.20), p = 0.02] analysis. In a comparative analysis, we found that GLR (G) and PLR (H) levels were significantly higher in participants with Pf infections compared to participants without Pf infection ( p < 0.05). We also found that women with a history of miscarriage had considerably higher sHLA-G levels [50.14 (36.30–71.00) vs. 35.44(31.84–42.72)] than women with no history of miscarriage. Conclusion Pf infection in pregnant Ghanaian women was associated with elevated ALP, GLR, and PLR, indicating hepatic dysfunction and systemic inflammation. The non-use of IPTp-SP among pregnant women was significantly associated with active Pf infection, highlighting the importance of chemoprophylaxis. Increased sHLA-G levels in women with miscarriage suggest an immunological link to pregnancy loss. Further prospective investigation of sHLA-G as a biomarker of adverse pregnancy outcome in malaria-endemic settings with a larger sample size is required.