Complications of Immunosuppression in Solid Organ Transplantation
Stephen M. Cohn, Matthew O. Dolich in Complications in Surgery and Trauma, 2014
Short-term patient survival rates have progressively improved with the introduction of new immunosuppressive drugs to the levels where it is difficult to establish differences in survival among the immunosuppressive agents used. Long-term studies are required to confirm the short-term results. Corticosteroids and cyclosporine have stronger impact on blood pressure and lipid profile than tacrolimus. Tacrolimus is associated with higher incidence of NODM. Steroid withdrawal and CNI withdrawal improve cardiovascular risk profile; however, studies have not shown that this strategy decreases mortality from cardiovascular events. Malignancies and infections still remain important causes of morbidity and mortality. Clearly, there is a pressing clinical need to develop novel immunosuppressive agents that are more specific yet less toxic. In addition, research and discovery on ways to induce immune tolerance will help reduce the need for lifelong immunosuppression and help decrease the incidence of rejection, cancers, and infections.
Uterine transplantation and lessons from transplant surgery
J. Richard Smith, Giuseppe Del Priore, Robert L. Coleman, John M. Monaghan in An Atlas of Gynecologic Oncology, 2018
Other lessons from transplant research can be applied to seemingly unrelated areas of medicine, such as randomized control trials on immunosuppressive therapy. For instance, organ transplant and immunosuppression therapy have been reported to significantly change a recipient’s allergic reaction profile. A recipient who is allergic to certain items, such as peanuts, may no longer be allergic after receiving a transplanted organ and subsequent immunosuppressive medications. Theoretically, a child with a peanut allergy could be treated with a very short course of immunosuppressants, and then over days repeatedly exposed to the allergen. By slowly weaning the immunosuppressant regimen, the allergic patients would become tolerant as they emerge from the induced immunosuppression. This is possible given current encouraging results in solid organ transplant-induced immune tolerance.
Life Care Planning for Organ Transplantation
Roger O. Weed, Debra E. Berens in Life Care Planning and Case Management Handbook, 2018
Rejection continues to represent one of the most common causes of graft failure. With an intact immune system, the body's natural response to a newly transplanted organ is rejection. Specific lymphocytes within the immune system recognize the genetic blueprint of anything that is not native to the recipient. As a result of advances in HLA typing and cross-matching, hyperacute rejection today is almost extinct, although chronic rejection remains a serious unsolved complication. Organs donated and received between identical twins are the only transplants that are widely accepted as not requiring comprehensive immunosuppression. Research continues on reaching immune tolerance through immunosuppressive withdrawal, as well as bone marrow transplantation at the time of solid organ transplant. A wide spectrum of improved immunosuppressive agents that have contributed significantly to a drastic reduction in the incidence of acute cellular rejection for most transplanted organs is now available.
Immunomodulatory nano-preparations for rheumatoid arthritis
Published in Drug Delivery, 2023
Chenglong Li, Yangyun Han, Xianjin Luo, Can Qian, Yang Li, Huaiyu Su, Guangshen Du
Currently, the first- or second-line medications, including conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs), targeted synthetic DMARDs, biological DMARDs, and glucocorticoids (GCs), function primarily by suppressing the immune system to varying degrees. These procedures inevitably raise the danger of infection and malignancy, and once the course of therapy is stopped, the autoimmune reaction will recur or become even more severe. In addition, a substantial percentage of patients with RA still show insufficient responses to those medications, such as 30% and 37% for methotrexate (MTX) and biologics, respectively (Moulis et al., 2018; Szostak et al., 2020). As an alternative therapy for immunosuppression, antigen-specific immune tolerance, a strategy based on the principle of recognizing the target antigen of autoimmune inflammatory attack and using it to stimulate the immune system to attenuate antigen-specific attack (Shakya & Nandakumar, 2018), means that the immune system retains the ability to respond to other antigens or injuries while lacking the destructive immune response to specific antigens (Serra & Santamaria, 2019). This idea was employed to treat allergy disorders over a century ago (Noon, 1911).
Melanocortin 5 Receptor Expression and Recovery of Ocular Immune Privilege after Uveitis
Published in Ocular Immunology and Inflammation, 2022
Tat Fong Ng, Ambika Manhapra, David Cluckey, Yoona Choe, Srujan Vajram, Andrew W. Taylor
The eye has adapted within its tissue microenvironment several mechanisms, which work to prevent and suppress the activation of inflammation that establishes immune privilege.1 The mechanisms of immune privilege are mediated in part by neuropeptides produced within the eye. These molecules mediate localized suppression of inflammation, prevent activation of effector T cells, and promote immune tolerance to antigen expressed within the eye. An essential mediator of these immunomodulating mechanisms is the neuropeptide alpha-melanocyte-stimulating hormone (α-MSH).1–3 The neuropeptide α-MSH is constitutively expressed within the eye, and retinal pigment epithelial cells (RPE) are a source of α-MSH.4,5 In the aqueous humor, α-MSH mediates aqueous humor suppression of effector T cell activation and induces T cell production of TGF-β that further suppresses immune cell activity.6 In the conditioned media of RPE-eyecups, α-MSH suppresses pro-inflammatory activity, promotes anti-inflammatory cytokine production, alters the maturation of phagosomes, and induces suppressor cell activity in macrophages.5,7–12
Kinin B1 receptors as a therapeutic target for inflammation
Published in Expert Opinion on Therapeutic Targets, 2018
Fatimunnisa Qadri, Michael Bader
Inflammatory autoimmune diseases are chronic inflammatory diseases of yet unknown etiology. The main factors facilitating autoimmune diseases are genetic susceptibility, epigenetic factors, and immune deregulation or defective/impaired immune tolerance. These factors are believed to be responsible for the attack of self-antigens by autoreactive leukocytes, especially lymphocytes, resulting in tissue injury [177]. These diseases can be systemic or affect a particular organ or tissue, such as brain, multiple sclerosis; digestive tract, Crohn’s disease, inflammatory bowel disease, and ulcerative colitis; endocrine glands, diabetes mellitus type I, and Grave’s disease; skin, psoriasis; systemic, rheumatoid arthritis, and systemic lupus [178]. Excessive and prolonged activation of immune cells, such as T and B lymphocytes, and overexpression of pro-inflammatory cytokine TNFα, IL-6, IL-1, IFNγ, and the NF-kB-associated signaling pathway play a central role in the pathogenesis of autoimmune inflammatory responses [179]. Increasing amounts of data suggest that BKB1R are involved in the development of autoimmune diseases such as multiple sclerosis [180,181]; Crohn’s disease, ulcerative colitis and inflammatory bowel disease [182–184], and diabetes mellitus type I [136,185–187].
Related Knowledge Centers
- Allergen
- Central Tolerance
- Lymph Node
- Peripheral Tolerance
- Thymus
- Bone Marrow
- Immune System
- Antigen
- Immune Response
- Gut Microbiota