ArticleArthritis and rheumatism2013
Multiple lupus-associated ITGAM variants alter Mac-1 functions on neutrophils.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 57 citations in OpenAlex.
- Complement gene variants in relation to autoantibodies to beta cell specific antigens and type 1 diabetes in the TEDDY Study.Scientific reports · 2016Trial
- Mac-1 regulates disease stage-specific immunosuppression via the nitric oxide pathway in autoimmune disease.Science advances · 2025Article
- Identification of a potential miRNA-mRNA regulatory network for ischemic stroke by using bioinformatics methods: a retrospective study based on the Gene Expression Omnibus database.Frontiers in immunology · 2025Article
- Gut microbiota dysbiosis aggravates sepsis-induced lung injury by promoting neutrophil extracellular traps and suppressing host integrin defense.Frontiers in microbiology · 2025Article
- The integrin CD11b inhibits MSU-induced NLRP3 inflammasome activation in macrophages and protects mice against MSU-induced joint inflammation.Arthritis research & therapy · 2024Article
- Targeting Neutrophil βBiomolecules · 2023Review
- CD11b agonists offer a novel approach for treating lupus nephritis.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Loss of CD11b Accelerates Lupus Nephritis in Lyn-Deficient Mice Without Disrupting Glomerular Leukocyte Trafficking.Frontiers in immunology · 2022Article
- Immunogenetics of Lupus Erythematosus.Advances in experimental medicine and biology · 2022Article
- Clinical features and expression of type I interferon-inducible genes in systemic lupus erythematosus patients harboring rs1143679 polymorphism in China: a single-center, retrospective study.Clinical rheumatology · 2021Article
- A Genetic Model of Constitutively Active Integrin CD11b/CD18.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Heterogeneity in neutrophil responses to immune complexes.Blood advances · 2019Article
- Mice expressing the variant rs1143679 allele of ITGAM (CD11b) show impaired DC-mediated T cell proliferation.Mammalian genome : official journal of the International Mammalian Genome Society · 2019Article
- Exploring the etiopathogenesis of systemic lupus erythematosus: a genetic perspective.Immunogenetics · 2019Review
- Infection with Opportunistic Bacteria Triggers Severe Pulmonary Inflammation in Lupus-Prone Mice.Mediators of inflammation · 2019Article
- MiR-21 binding site SNP within ITGAM associated with psoriasis susceptibility in women.PloS one · 2019Article
- Evidence for a direct link between PAD4-mediated citrullination and the oxidative burst in human neutrophils.Scientific reports · 2018Article
- Complement Factor H Inhibits Anti-Neutrophil Cytoplasmic Autoantibody-Induced Neutrophil Activation by Interacting With Neutrophils.Frontiers in immunology · 2018Article
- Perspective on Protein Arginine Deiminase Activity-Bicarbonate Is a pH-Independent Regulator of Citrullination.Frontiers in immunology · 2018Article
- CD11b Activity Modulates Pathogenesis of Lupus Nephritis.Frontiers in medicine · 2018Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveMultiple studies have demonstrated that single-nucleotide polymorphisms (SNPs) in the ITGAM locus (including the nonsynonymous SNPs rs1143679, rs1143678, and rs1143683) are associated with systemic lupus erythematosus (SLE). ITGAM encodes the protein CD11b, a subunit of the β2 integrin Mac-1. The purpose of this study was to determine the effects of ITGAM genetic variation on the biologic functions of neutrophil Mac-1.
methodsNeutrophils from ITGAM-genotyped and -sequenced healthy donors were isolated for functional studies. The phagocytic capacity of neutrophil ITGAM variants was probed with complement-coated erythrocytes, serum-treated zymosan, heat-treated zymosan, and IgG-coated erythrocytes. The adhesion capacity of ITGAM variants, in adhering to either purified intercellular adhesion molecule 1 or tumor necrosis factor α-stimulated endothelial cells, was assessed in a flow chamber. Expression levels of total CD11b and activation of CD11b were assessed by flow cytometry.
resultsMac-1-mediated neutrophil phagocytosis, determined in cultures with 2 different complement-coated particles, was significantly reduced in individuals with nonsynonymous variant alleles of ITGAM. This reduction in phagocytosis was related to variation at either rs1143679 (in the β-propeller region) or rs1143678/rs1143683 (highly linked SNPs in the cytoplasmic/calf-1 regions). Phagocytosis mediated by Fcγ receptors was also significantly reduced in donors with variant ITGAM alleles. Similarly, firm adhesion of neutrophils was significantly reduced in individuals with variant ITGAM alleles. These functional alterations were not attributable to differences in total receptor expression or activation.
conclusionThe nonsynonymous ITGAM variants rs1143679 and rs1143678/rs113683 contribute to altered Mac-1 function on neutrophils. These results underscore the need to consider multiple nonsynonymous SNPs when assessing the functional consequences of ITGAM variation on immune cell processes and the risk of SLE.
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