Sequence variants in the ITGB2 gene underlying leukocyte adhesion deficiency Type-1 in four consanguineous families

Raza, Rubab; Khalid, Zara; Zaman, Atteaya; Jafar, Sadaf; Anwar, Muhammad Zeeshan; Hassan, Syed Waqas; Iqbal, Momin; Rashid, Sajid; Ahmad, Wasim; Raza, Syed M.

doi:10.1016/j.genrep.2022.101699

Cited by 3 publications

(1 citation statement)

References 19 publications

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“…The other DEP nodes at P2 were found to participate in protein synthesis, ribosome biogenesis, and cellular trafficking. The observed differential expression of Integrin Subunit Beta 2 (ITGB2) between ASC‐EVs and BMSC‐EVs at P4 and P8 implies significantly different capacities to promote wound healing and various immune cell functions (Raza et al., 2022 ). The remaining nine DEP nodes at P4 mainly play roles in ubiquitination and protein degradation, while at P8 they are involved in a wide range of biological processes, such as intracellular transport, mRNA processing and metabolism, and cell adhesion and signalling.…”

Section: Resultsmentioning

confidence: 99%

Mesenchymal stromal/stem cell tissue source and in vitro expansion impact extracellular vesicle protein and miRNA compositions as well as angiogenic and immunomodulatory capacities

Liu,

Sun,

et al. 2024

J of Extracellular Vesicle

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Recently, therapies utilizing extracellular vesicles (EVs) derived from mesenchymal stromal/stem cells (MSCs) have begun to show promise in clinical trials. However, EV therapeutic potential varies with MSC tissue source and in vitro expansion through passaging. To find the optimal MSC source for clinically translatable EV‐derived therapies, this study aims to compare the angiogenic and immunomodulatory potentials and the protein and miRNA cargo compositions of EVs isolated from the two most common clinical sources of adult MSCs, bone marrow and adipose tissue, across different passage numbers. Primary bone marrow‐derived MSCs (BMSCs) and adipose‐derived MSCs (ASCs) were isolated from adult female Lewis rats and expanded in vitro to the indicated passage numbers (P2, P4, and P8). EVs were isolated from the culture medium of P2, P4, and P8 BMSCs and ASCs and characterized for EV size, number, surface markers, protein content, and morphology. EVs isolated from different tissue sources showed different EV yields per cell, EV sizes, and protein yield per EV. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of proteomics data and miRNA seq data identified key proteins and pathways associated with differences between BMSC‐EVs and ASC‐EVs, as well as differences due to passage number. In vitro tube formation assays employing human umbilical vein endothelial cells suggested that both tissue source and passage number had significant effects on the angiogenic capacity of EVs. With or without lipopolysaccharide (LPS) stimulation, EVs more significantly impacted expression of M2‐macrophage genes (IL‐10, Arg1, TGFβ) than M1‐macrophage genes (IL‐6, NOS2, TNFα). By correlating the proteomics analyses with the miRNA seq analysis and differences observed in our in vitro immunomodulatory, angiogenic, and proliferation assays, this study highlights the trade‐offs that may be necessary in selecting the optimal MSC source for development of clinical EV therapies.

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Section: Resultsmentioning

confidence: 99%

Mesenchymal stromal/stem cell tissue source and in vitro expansion impact extracellular vesicle protein and miRNA compositions as well as angiogenic and immunomodulatory capacities

Liu,

Sun,

et al. 2024

J of Extracellular Vesicle

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Sequence variants underlying severe combined immunodeficiency and leukocyte adhesion deficiency type 1 in six consanguineous families

Fayyaz,

Zaman,

Haider

et al. 2024

Immunogenetics

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Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

Saad,

Alkady,

Eldash

et al. 2024

J Clin Immunol

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Purpose Leukocyte adhesion deficiency (LAD) represents a rare group of inherited inborn errors of immunity (IEI) characterized by bacterial infections, delayed umbilical stump separation, and autoimmunity. This single-center study aimed at describing the clinical, immunological, and molecular characterizations of 34 LAD-I Egyptian pediatric patients. Methods Details of 34 patients’ personal medical history, clinical and laboratory findings were recorded; Genetic material from 28 patients was studied. Mutational analysis was done by Sanger sequencing. Results Omphalitis, skin and soft tissue infections with poorly healing ulcers, delayed falling of the umbilical stump, and recurrent or un-resolving pneumonia were the most common presentations, followed by chronic otitis media, enteropathy, periodontitis; and recurrent oral thrush. Persistent leukocytosis and neutrophilia were reported in all patients, as well as CD18 and CD11b deficiency. CD18 expression was < 2% in around 90% of patients. Sixteen different pathological gene variants were detected in 28 patients who underwent ITGß2 gene sequencing, of those, ten were novel and six were previously reported. Three families received a prenatal diagnosis. Patients were on antimicrobials according to culture’s results whenever available, and on prophylactic Trimethoprim-Sulfamethoxazole 5 mg/kg once daily, with regular clinical follow up. Hematopoietic stem cell transplantation (HSCT) was offered for 4 patients. However due to severity of the disease and delay in diagnosis, 58% of the patients passed away in the first 2 years of life. Conclusion This study highlights the importance of early diagnosis and distribution of ITGß2 gene mutation in Egyptian children. Further molecular studies, however, remain a challenging necessity for better disease characterization in the region.

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Sequence variants in the ITGB2 gene underlying leukocyte adhesion deficiency Type-1 in four consanguineous families

Cited by 3 publications

References 19 publications

Mesenchymal stromal/stem cell tissue source and in vitro expansion impact extracellular vesicle protein and miRNA compositions as well as angiogenic and immunomodulatory capacities

Mesenchymal stromal/stem cell tissue source and in vitro expansion impact extracellular vesicle protein and miRNA compositions as well as angiogenic and immunomodulatory capacities

Sequence variants underlying severe combined immunodeficiency and leukocyte adhesion deficiency type 1 in six consanguineous families

Analysis of Clinical, Immunological and Molecular Features of Leukocyte Adhesion Deficiency Type I in Egyptian Children

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