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Little attention has been devoted to the role of HLA‐G gene and molecule on parasitic disorders, and the available studies have focused on malaria, African and American trypanosomiasis, leishmaniosis, toxoplasmosis and echinococcosis. After reporting a brief description regarding the role of the cells of innate and adaptive immune system against parasites, we reviewed the major features of the HLA‐G gene and molecule and the role of HLA‐G on the major cells of immune system. Increased levels of soluble HLA‐G (sHLA‐G) have been observed in patients presenting toxoplasmosis and in the active phase of echinococcosis. In addition, increased sHLA‐G has also been associated with increased susceptibility to malaria and increased susceptibility to develop human African trypanosomiasis (HAT). In contrast, decreased membrane‐bound HLA‐G has been reported in placenta of patients infected with Plasmodium falciparum and in heart and colon of patients presenting Chagas disease. The 3′ untranslated region of the HLA‐G gene has been the main focus of studies on malaria, HAT and Chagas disease, exhibiting distinct patterns of associations. Considering that HLA‐G is an immune checkpoint molecule, inhibiting the activity of several cells of the immune system, the excessive neoexpression and the increased sHLA‐G levels together with the decreased constitutive tissue expression of membrane‐bound HLA‐G may be detrimental to the host infected with parasite agents. [ABSTRACT FROM AUTHOR]

Host and Plasmodium interactions result in highly variable clinical phenotypes, partly explained by the nature and level of anti-malarial antibody response. Human leukocyte antigen ( HLA)-G can create a tolerogenic environment, allowing parasites to escape from anti-malarial immunity. We performed a family-based association study encompassing 483 Sereer individuals (261 children and their parents), and reported two independent signals at the HLA-G 3′ untranslated region associated with antibody response to specific Plasmodium falciparum blood stage antigens, previously associated with malaria protection: (i) + 3010G together with + 3142C with total IgG and IgG1 against GLURP and (ii) + 3196G with IgG3 against MSP2. While these results require further investigation, they suggest for the first time a role of HLA-G in the regulation of humoral immune response in malaria. [ABSTRACT FROM AUTHOR]

We have previously shown that antibody responses directed to Plasmodium falciparum merozoite surface protein (MSP)-1, MSP-2 and glutamate-rich protein (GLURP) are associated with anti-malarial protection in residents of the Niakhar area of Senegal. In the same area, urinary schistosomiasis is frequent and we therefore assessed the possible influence of Schistosoma haematobium infection on these protective anti-malarial IgG responses. After adjustment for confounders, we found that the levels of IgG1 directed to MSP1 and GLURP were significantly lower in helminth carriers. The higher circulating levels of interleukin (IL)-10 present in the plasma of co-infected individuals were associated with decreased anti-plasmodial IgG responses, particularly of those directed to MSP-2. Our data thus reveal a modulation of P. falciparum-specific immune responses in the presence of a trematode helminth infection, potentially increasing infected individuals' risk of plasmodial infection or disease. [ABSTRACT FROM AUTHOR]

Structural variation in the human genome can affect risk of disease. An example is a complex structural variant of the human glycophorin gene cluster, called DUP4, which is associated with a clinically significant level of protection against severe malaria. The human glycophorin gene cluster harbours at least 23 distinct structural variants, and accurate genotyping of this complex structural variation remains a challenge. Here, we use a polymerase chain reaction-based strategy to genotype structural variation at the human glycophorin gene cluster, including the alleles responsible for the U- blood group. We validate our approach, based on a triplex paralogue ratio test, on publically available samples from the 1000 Genomes project. We then genotype 574 individuals from a longitudinal birth cohort (Tori-Bossito cohort) using small amounts of DNA at low cost. Our approach readily identifies known deletions and duplications, and can potentially identify novel variants for further analysis. It will allow exploration of genetic variation at the glycophorin locus, and investigation of its relationship with malaria, in large sample sets at minimal cost, using standard molecular biology equipment., (© 2020 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd.)