Publications by authors named "Basmah Al Dulaijan"

5 Publications

  • Page 1 of 1

Irritable bowel syndrome is strongly associated with the primary and idiopathic mast cell disorders.

Neurogastroenterol Motil 2021 Sep 17:e14265. Epub 2021 Sep 17.

University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.

Background: Mounting evidence supports a mechanistic association between irritable bowel syndrome (IBS) symptoms and mast cell hyperactivity. Yet, association between IBS and mast cell disorders (MCDs) has not been studied. We examined this association using two large databases and verified with manual chart review.

Methods: The IBM Watson Health Explorys database (Somers, NY), an aggregate of electronic health record (EHR) data from over two dozen US healthcare systems, and Epic's SlicerDicer tool, a self-service tool containing de-identified data from the Epic EHR, were used to identify patients with IBS and MCDs. Patients with organic gastrointestinal disease or diseases associated with secondary mast cell hyperproliferation were excluded. Results were verified with manual chart review from two academic centers.

Key Results: Up to 4% of IBS patients had a comorbid MCD. IBS was strongly associated with all MCDs. The strongest association was between IBS and mast cell activation syndrome (OR 16.3; 95% CI 13.1-20.3). Odds ratios for IBS+urticaria, IBS+idiopathic urticaria, IBS+non-malignant mastocytosis, and IBS+mast cell malignancy ranged from 4.5 to 9.9. Patients from each of these overlap cohorts were predominantly female, and the overlap occurred with all IBS subtypes. Thorough endoscopic evaluation and comorbid mood disorders and migraines are more common in the overlap cohorts than in IBS alone.

Conclusions/inferences: In a large US database encompassing >53 million patients over >20 years, patients with IBS are at least 4 times more likely to have a MCD than the general population. Further study of mast cell involvement in the pathogenesis of IBS is warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/nmo.14265DOI Listing
September 2021

ACTH treatment promotes murine cardiac allograft acceptance.

JCI Insight 2021 Jul 8;6(13). Epub 2021 Jul 8.

Transplantation Research Center.

Heart transplantation is the optimal therapy for patients with end-stage heart disease, but its long-term outcome remains inadequate. Recent studies have highlighted the importance of the melanocortin receptors (MCRs) in inflammation, but how MCRs regulate the balance between alloreactive T cells and Tregs, and whether they impact chronic heart transplant rejection, is unknown. Here, we found that Tregs express MC2R, and MC2R expression was highest among all MCRs by Tregs. Our data indicate that adrenocorticotropic hormone (ACTH), the sole ligand for MC2R, promoted the formation of Tregs by increasing the expression of IL-2Rα (CD25) in CD4+ T cells and activation of STAT5 in CD4+CD25+ T cells. ACTH treatment also improved the survival of heart allografts and increased the formation of Tregs in CD28KO mice. ACTH treatment synergized with the tolerogenic effect of CTLA-4-Ig, resulting in long-term survival of heart allografts and an increase in intragraft Tregs. ACTH administration also demonstrated higher prolongation of heart allograft survival in transgenic mouse recipients with both complete KO and conditional KO of PI3Kγ in T cells. Finally, ACTH treatment reduced chronic rejection markedly. These data demonstrate that ACTH treatment improved heart transplant outcomes, and this effect correlated with an increase in Tregs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.143385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8410061PMC
July 2021

Regulatory T cells engineered with TCR signaling-responsive IL-2 nanogels suppress alloimmunity in sites of antigen encounter.

Sci Transl Med 2020 11;12(569)

Transplantation Research Center, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.

Adoptive cell transfer of ex vivo expanded regulatory T cells (T) has shown immense potential in animal models of auto- and alloimmunity. However, the effective translation of such T therapies to the clinic has been slow. Because T homeostasis is known to require continuous T cell receptor (TCR) ligation and exogenous interleukin-2 (IL-2), some investigators have explored the use of low-dose IL-2 injections to increase endogenous T responses. Systemic IL-2 immunotherapy, however, can also lead to the activation of cytotoxic T lymphocytes and natural killer cells, causing adverse therapeutic outcomes. Here, we describe a drug delivery platform, which can be engineered to autostimulate T with IL-2 in response to TCR-dependent activation, and thus activate these cells in sites of antigen encounter. To this end, protein nanogels (NGs) were synthesized with cleavable bis(-hydroxysuccinimide) cross-linkers and IL-2/Fc fusion (IL-2) proteins to form particles that release IL-2 under reducing conditions, as found at the surface of T cells receiving stimulation through the TCR. T surface-conjugated with IL-2 NGs were found to have preferential, allograft-protective effects relative to unmodified T or T stimulated with systemic IL-2. We demonstrate that murine and human NG-modified T carrying an IL-2 cargo perform better than conventional T in suppressing alloimmunity in murine and humanized mouse allotransplantation models. In all, the technology presented in this study has the potential to improve T transfer therapy by enabling the regulated spatiotemporal provision of IL-2 to antigen-primed T.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1126/scitranslmed.aaw4744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8519505PMC
November 2020

Regulatory T Cells for More Targeted Immunosuppressive Therapies.

Clin Lab Med 2019 03 20;39(1):1-13. Epub 2018 Dec 20.

Transplantation Research Center, Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. Electronic address:

There has been a prolific amount of research dedicated to the T-regulatory cells (Tregs) and their role in achieving immune homeostasis. Here, the authors briefly discuss the known biology, utilization, and potential of Tregs, for current trials and future immunotherapy. Most current trials of Treg therapies include either ex vivo expanded Tregs transferred into the peripheral blood of patients with diseases of immunologic origin or interleukin 2 injected to stimulate Tregs directly. Ongoing trials designed to measure the clinical efficacy and safety profile of these novel therapeutic approaches have resulted in largely favorable outcomes in a variety of autoimmune and alloimmune diseases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cll.2018.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501202PMC
March 2019

Regulatory T cells: from the bench to the clinic and back.

Curr Opin Organ Transplant 2018 02;23(1):1-7

Basmah S. Al Dulaijan and Amr Mansouri contributed equally to the article.

Purpose Of Review: The main objective of this review is to briefly highlight how we gradually came to understand regulatory T cells (Tregs) and forkhead box p3 (FoxP3) biology, including their function and regulation. We will also discuss how this knowledge is being translated into the clinical setting and the significant challenges that need to be overcome.

Recent Findings: CD4FoxP3 Tregs are key players in immune regulation. Their deficiency and dysfunction have been implicated in the pathogenesis of many autoimmune diseases. This has led towards extensive work across the years to figure out the biology and suppressive mechanisms of these cells. Furthermore, Tregs' ability to suppress immune responses makes the idea of their utilization in adoptive immunotherapy appealing. Work has been underway to establish ideal methods to integrate Tregs into the management of autoimmune diseases and alloimmunity, either by treatment with IL-2 or infusion of ex-vivo expanded Tregs. Despite Tregs' scarcity and increased tendency for Activation-induced cell death, many groups have developed effective methods to expand them ex vivo.

Summary: Although clinical trials are ongoing to test the safety and efficacy of regulatory cells in transplant recipients, it is vital to continue exploring the cellular and molecular mechanisms that control their stability and homeostasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOT.0000000000000491DOI Listing
February 2018
-->