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Immunomodulating Agents in Gastrointestinal Disease
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Samir A. Shah, Athos Bousvaros, A. Christopher Stevens
Monoclonal therapies that block leukocyte adhesion have been suggested for the treatment of intestinal diseases. CD18 is a molecule in the integrin family that forms heterodimers with CD11 isotype molecules. CD18/CD11 is a leukocyte adhesion molecule expressed on vascular endothelium and the basolateral surfaces of epithelial cells. Anti-CD18 antibody blocks the adhesion of leukocytes to these sites, preventing extravasation of leukocytes into tissues and across epithelial barriers [204,205]. Pretreatment with anti-CD 18 has been effective in preventing the colonic inflammation in the TNBS rabbit model of colitis [206]; however, it remains untested in humans. Another integrin, very late antigen (VLA4), functions in the adhesion of leukocytes and has been a target of monoclonal antibody therapy in the treatment of the cotton-topped tamarin animal model of ulcerative colitis [207].
Overview of Cell Adhesion Molecules and Their Antagonism
Published in Bruce S. Bochner, Adhesion Molecules in Allergic Disease, 2020
A relevant consideration in antiadhesion therapy is the potential for adverse effects, particularly increased susceptibility to infection. This is supported by two human immunodeficiencies, leukocyte adhesion deficiency (LAD) types 1 and 2, that are characterized, respectively, by deficiencies of CD11/CD18 and selectin ligand. Moreover, in some animal studies, an increased proclivity for infection has been noted as a sequela of antiadhesion therapy (50). The risk of infection may be affected by the choice of target. For example, it might be expected that targeting ICAM-1, which is up-regulated at inflammatory sites in comparison to normal tissue, might be less immunosuppressive than targeting CD18, which is present on all leukocytes. Support for this comes from knockout animals, where it has been shown that ICAM-1 deficient mice do not appear excessively susceptible to infection. Similarly, targeting VLA-4, which is expressed on all leukocytes with the exception of neutrophils, might conceivably engender less global immune suppression by leaving neutrophil function intact. Nevertheless, heightened vigilance for sequelae of immunosuppression is required for all studies using antiadhesion therapies.
Host Defense I: Non-specific Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
In the lazy leukocyte syndrome, granulocytes exhibit impaired chemotaxis and motility. This is due to an abnormal distribution of actin filaments within phagocytic cells. These patients have increased susceptibility to bacterial infections, especially agents invading the skin and mucous membranes. An inability to synthesize the CD18 molecule results in leukocyte adhesion deficiency, described above.
Identification and verification of pivotal genes promoting the progression of atherosclerosis based on WGCNA
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2023
Jing Wen, Tong Ren, Jinzhen Zheng, Xing Jiang, Yingxia Li, Xilin Jiang, Xin Jin, Hongying Zhao, Jingwen Li
Both innate and adaptive immune systems play a key role in driving chronic vascular inflammation related with AS [27]. In order to explore the role of pivotal genes in the immunity of AS, the analysis results of ssGSEA used in this study showed that the expression level of immune-related genes in advanced atherosclerotic tissues was significantly up-regulated. The expression of ITGB2 (CD18) was positively correlated with the infiltration of Tregs, while the infiltration of plasma cells was negatively correlated with the expression of ITGAM. In the study of psoriasis, researchers found that the reduced expression of CD18 can weaken the contact between Tregs and DCs, TGF-beta-dependent suppressive function of Tregs requires wild-type levels of CD18 [28]. Studies showed that the loss of CD11b during autoimmune process led to the increase of IgG Ab and plasma cells, which also confirmed that the infiltration of plasma cells was negatively related to the expression of CD11b [29]. However, the mechanism of pivotal genes screened in this study on the infiltration of atherosclerotic immune cells still lacks in-depth researches, hence is needed to explore its specific mechanism in the future.
BST-1 as a serum protein biomarker involved in neutrophil infiltration in schizophrenia
Published in The World Journal of Biological Psychiatry, 2022
Liang-Jen Wang, Yu-Chi Huang, Pao-Yen Lin, Yu Lee, Chi-Fa Hung, Su-Ting Hsu, Lien-Hung Huang, Sung-Chou Li
Bone marrow stromal cell antigen-1 (BST1) is a protein marker that we identified in this study. A stromal cell line-derived glycosylphosphatidylinositol-anchored molecule, BST1 facilitates pre-B-cell growth (Kaisho et al. 1994). It plays a role in neutrophil adhesion, calcium homeostasis, promotes polarisation and transendothelial migration through associates with the CD11b/CD18 complex for signal transduction (Funaro et al. 2004; Malavasi et al. 2006; Ortolan et al. 2006). BST1 overexpression in the stromal cell population has been associated with polyclonal B-cell abnormalities in rheumatoid arthritis (Wang et al. 2015; Liu et al. 2016). BST1 is also involved in the maintenance of stemness in Mesenchymal stem cells through various processes like self-renewal, migration, and differentiation (Chosa and Ishisaki 2018). Furthermore, associations between single-nucleotide polymorphisms (SNPs) of the CD157/BST1 gene and ASD were found in a Japanese population (Yokoyama et al. 2015). Therefore, BST1 may be involved in the dopamine metabolite pathway and associated with a susceptibility to schizophrenia.
Gene therapy for primary immunodeficiencies: up-to-date
Published in Expert Opinion on Biological Therapy, 2021
Leukocyte Adhesion Deficiency 1 (LAD-1) is an autosomal recessive disorder of impaired neutrophil migration to sites of infection, resulting in severe, recurrent bacterial infections. Pathogenic variants in the ITGB2 gene lead to defective membrane expression of the CD18 integrin subunit on leukocytes, crucial for neutrophil migration. Without curative allogeneic HSCT, children do not survive beyond infancy. Early trials using a γRV vector in two patients without pre-conditioning led to poor outcomes, with no gene marked cells detectable peripherally after two months [74]. Subsequent pre-clinical work undertaken in murine and canine models has been successful, leading to in-human trials using busulfan conditioning for patients without access to an HLA-identical sibling donor [75,76] (NCT03825783, NCT03812263).