Human leukocyte antigen class-II DRB1 alleles and Giardia lamblia infection in children: A case-control study

El-Beshbishi, Samar N.; Elblihy, Ayat; Atia, Raefa A; Megahed, Ahmed; Auf, Fatma A

doi:10.4103/1995-7645.275413

Cited by 2 publications

(3 citation statements)

References 2 publications

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“…In this study, 26 epitopes are proposed to activate CD4+ cells due to their high affinity to several MHC class II molecules. First, four MHC class II alleles were chosen, the MHC class II I-A k and I-A d that are expressed in mice widely used as model for giardiasis, as well as the HLA-DRB1 * 03: 01 and HLA-DRB1 * 13: 01 alleles that are related to an increased risk of G. lamblia infection ( AL-Khaliq et al., 2020 ; El-Beshbishi et al., 2020 ). MHC class II molecules are expressed in dendritic cells and B lymphocytes, which are chemoattracted by trophozoite-stimulated epithelial cells ( Roxström-Lindquist et al., 2005 ).…”

Section: Discussionmentioning

confidence: 99%

“…Those MHC molecules are expressed on the C3H/He and BALB/c mouse models, respectively, which are mouse strains frequently used in giardiasis studies ( Belosevic et al., 1984 ; Venkatesan et al., 1997 ; Larocque et al., 2003 ; Lee et al., 2014 ; Serradell et al., 2019 ; Garzon et al., 2020 ). The HLA-DRB1*03:01 and HLA-DRB1*13:01 human MHC class II molecules were selected due to their probable association with susceptibility to infection ( AL-Khaliq et al., 2020 ; El-Beshbishi et al., 2020 ). The proteins Hen Egg-white Lysozyme (HEL) and ovalbumin (Ova) were used as control antigens for the epitope prediction of MHC class II alleles (I-A k and I-A d , respectively).…”

Section: Methodsmentioning

confidence: 99%

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“Immunoinformatic Identification of T-Cell and B-Cell Epitopes From Giardia lamblia Immunogenic Proteins as Candidates to Develop Peptide-Based Vaccines Against Giardiasis”

Garzon

Ortega-Tirado

Lopez-Romero

et al. 2021

Front. Cell. Infect. Microbiol.

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Giardiasis is one of the most common gastrointestinal infections worldwide, mainly in developing countries. The etiological agent is the Giardia lamblia parasite. Giardiasis mainly affects children and immunocompromised people, causing symptoms such as diarrhea, dehydration, abdominal cramps, nausea, and malnutrition. In order to develop an effective vaccine against giardiasis, it is necessary to understand the host-Giardia interactions, the immunological mechanisms involved in protection against infection, and to characterize the parasite antigens that activate the host immune system. In this study, we identify and characterize potential T-cell and B-cell epitopes of Giardia immunogenic proteins by immunoinformatic approaches, and we discuss the potential role of those epitopes to stimulate the host´s immune system. We selected the main immunogenic and protective proteins of Giardia experimentally investigated. We predicted T-cell and B-cell epitopes using immunoinformatic tools (NetMHCII and BCPREDS). Variable surface proteins (VSPs), structural (giardins), metabolic, and cyst wall proteins were identified as the more relevant immunogens of G. lamblia. We described the protein sequences with the highest affinity to bind MHC class II molecules from mouse (I-Ak and I-Ad) and human (DRB1*03:01 and DRB1*13:01) alleles, as well as we selected promiscuous epitopes, which bind to the most common range of MHC class II molecules in human population. In addition, we identified the presence of conserved epitopes within the main protein families (giardins, VSP, CWP) of Giardia. To our knowledge, this is the first in silico study that analyze immunogenic proteins of G. lamblia by combining bioinformatics strategies to identify potential T-cell and B-cell epitopes, which can be potential candidates in the development of peptide-based vaccines. The bioinformatics analysis demonstrated in this study provides a deeper understanding of the Giardia immunogens that bind to critical molecules of the host immune system, such as MHC class II and antibodies, as well as strategies to rational design of peptide-based vaccine against giardiasis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“Immunoinformatic Identification of T-Cell and B-Cell Epitopes From Giardia lamblia Immunogenic Proteins as Candidates to Develop Peptide-Based Vaccines Against Giardiasis”

Garzon

Ortega-Tirado

Lopez-Romero

et al. 2021

Front. Cell. Infect. Microbiol.

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“…Documented studies have recorded associations between HLA class-II gene polymorphisms and development of resistance or susceptibility to several parasitic infections, as well as clinical variability [16,17] . Accordingly, El-Beshbishi et al [18] compared for the first time the genotype frequencies of HLA class-II DRB1 alleles in G. lambliainfected children and in children free of any enteric pathogens. The investigators demonstrated that HLA class-II DRB1*03:01 as well as DRB1*13:01 alleles were significantly (P<0.001) associated with G. lamblia infection, while DRB1*04:02, DRB1*10:01, DRB1*14:01 and DRB1*15:01 alleles were significantly detected in control children, suggesting the involvement of those alleles in the establishment of host immune response to G. lamblia infection [16] .…”

Section: Introductionmentioning

confidence: 99%

Clinical characteristics versus human leukocyte antigen class-II DRB1 alleles profiles and fecal calprotectin level in Giardia lamblia-infected children

Elblihy

Megahed

Atia

et al. 2020

Parasitologists United Journal

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Background: Giardia lamblia is a global enteric protozoan causing giardiasis, a disease characterized by different clinical presentations ranging from loss of appetite, abdominal pain, steatorrhea, nausea, vomiting to severe malabsorption syndrome, but the majority of infected children are asymptomatic, especially in developing countries. The clinical outcome may be associated with fecal calprotectin released in the bowel in case of inflammation and human leukocyte antigen (HLA) class-II DRB1 alleles that play a crucial role in the immune system. Objectives: To reveal any association between fecal calprotectin and the development of symptomatic or asymptomatic giardiasis. Also, to highlight the influence of HLA class-II DRB1 alleles on clinical manifestations of G. lamblia-infected children. Subjects and Methods:The study included 160 children: 80 healthy children (control), 40 Giardiapositive children with gastrointestinal symptoms (symptomatic group), and 40 Giardia-positive children without gastrointestinal manifestations (asymptomatic group). Fecal calprotectin was measured using ELISA, and HLA class-II was typed by PCR. Results: The commonest presentation of giardiasis was abdominal pain. Fecal calprotectin level was elevated (141.40±67.7-183±48.21 µg/gm) in children with giardiasis, mainly among asymptomatic group. HLA class-II DRB1*03:01 and *13:01 alleles were significantly associated with incidence of giardiasis (P<0.0005). A significant association of the heterozygous allotype HLA-DRB1*03:01/03:02 was recorded with giardiasis manifestations, mainly abdominal pain (P=0.026). Conclusion:Fecal calprotectin can be used as a marker of G. lamblia-induced intestinal inflammation. HLA class-II DRB1*03 and DRB1*13 alleles likely underlie clinical variability of giardiasis. This association may clarify why giardiasis does not occur in significant number of children exposed to the parasite. Calprotectin versus HLA in giardiasisElBlihy et al.

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Human leukocyte antigen class-II DRB1 alleles and Giardia lamblia infection in children: A case-control study

Cited by 2 publications

References 2 publications

“Immunoinformatic Identification of T-Cell and B-Cell Epitopes From Giardia lamblia Immunogenic Proteins as Candidates to Develop Peptide-Based Vaccines Against Giardiasis”

“Immunoinformatic Identification of T-Cell and B-Cell Epitopes From Giardia lamblia Immunogenic Proteins as Candidates to Develop Peptide-Based Vaccines Against Giardiasis”

Clinical characteristics versus human leukocyte antigen class-II DRB1 alleles profiles and fecal calprotectin level in Giardia lamblia-infected children

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