Immunosenescence and Immune Response in Organ Transplantation

Martins, Paulo Ney Aguiar; Tullius, Stefan G.; Markmann, James F.

doi:10.3109/08830185.2013.829469

Cited by 38 publications

(29 citation statements)

References 132 publications

(123 reference statements)

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“…Furthermore, ATG may also suppress the B‐cell immune response . During immunosenescence, changes to the innate and adaptive immune systems cause the immune response to external pathogens to become less effective . ATG depletion coupled with aging‐related immune changes place elderly KTRs at an increased risk of bacterial and viral infections, which was observed in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Assessment of infectious complications in elderly kidney transplant recipients receiving induction with anti‐thymocyte globulin vs basiliximab

Pham

Kuten

Knight

et al. 2020

Transplant Infectious Dis

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Background: Elderly transplant recipients experience lower rates of acute rejection with higher rates of infectious complications compared to their younger counterparts. While less intensive immunosuppression may be preferable, there are no recommendations for depleting versus non-depleting induction strategies. We sought to compare infectious complications between anti-thymocyte globulin (ATG) and basiliximab (IL2RA) induction in elderly kidney transplant recipients (KTRs). Methods:We reviewed 146 KTRs ≥65 years receiving ATG or IL2RA induction. Per institution protocol, ATG was administered to patients with the following characteristics, irrespective of age: African American (AA), PRA ≥20%, and/or re-transplantation. Infectious complications (bacterial, viral, and invasive fungal) at 1 year were compared.Results: There were significantly more AA, deceased donors, and sensitized KTRs in the ATG group, reflecting criteria for induction agent. ATG KTRs experienced higher rates of overall infectious complications (77% vs 56%, P = .01), driven by increased bacterial (54% vs 39%, P = .08) and viral infections (51% vs 35%, P = .05). Urinary tract infections (UTIs) and CMV in particular occurred at high rates among ATG patients (46% and 32%, respectively). In multivariate analysis, the only independent risk factor associated with increased risk for infection was induction with ATG (adjusted HR 1.71 [95% CI 1.04-2.83], P = .04). Overall rates of immunologic outcomes were low. Conclusion:Elderly KTRs receiving ATG are at an increased risk for infectious complications, largely attributed to high rates of UTIs and CMV. Additional strategies aimed at mitigating these complications in elderly patients requiring ATG may be beneficial.

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Section: Discussionmentioning

confidence: 99%

Assessment of infectious complications in elderly kidney transplant recipients receiving induction with anti‐thymocyte globulin vs basiliximab

Pham

Kuten

Knight

et al. 2020

Transplant Infectious Dis

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“…The results of our analysis remained similar after exclusion of the patients with overlap of AIH, so this apparent stronger immune-associated phenotype extends beyond a reported concomitant diagnosis of AIH. Age-related changes are known to occur in the immune system, and decreased rejection in older individuals has also been reported for transplant recipients of other solid organs and has been attributed to immunosenescence, involving alterations in the immune cell populations with age [27, 28]. In addition to affecting rates of rejection, maybe age-related changes in the immune system similarly affect the pathophysiology of PSC, resulting in a more aggressive immune-mediated disease in younger patients that is also associated with disease recurrence post-transplant.…”

Section: Discussionmentioning

confidence: 99%

Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis

et al. 2017

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Background There is increasing evidence for a heterogeneity of phenotypes in primary sclerosing cholangitis (PSC), but differences across the age spectrum in adults with PSC have not been well characterized. Aims To characterize phenotypic variations and liver transplantation outcomes by age group in adults with PSC. Methods The United Network for Organ Sharing database was used to identify waitlist registrations for primary liver transplantation in adults with PSC. Patients were split into three age groups: 18–39 (young), 40–59 (middle-aged), and ≥60 (older). Their clinical characteristics and outcomes on the waitlist and post-transplant were compared. Results Overall, 8272 adults with PSC were listed for liver transplantation during the study period, of which 28.9% were young, 52.0% were middle-aged, and 19.1% were older. The young age group had the greatest male predominance (70.0 vs. 66.2 vs. 65.1%, p = 0.001), the highest proportion of black individuals (20.0 vs. 11.0 vs. 5.5%, p <0.001), and the most patients listed with concomitant autoimmune hepatitis (2.2 vs. 1.0 vs. 0.8%, p <0.001). Older patients experienced the greatest waitlist and post-transplant mortality. Graft survival was greatest in the middle-aged group. Young patients were most likely to experience acute rejection (31 vs. 22.8 vs. 18.0%, p <0.001) and have graft failure due to chronic rejection or PSC recurrence (47.8 vs. 42.3 vs. 17.9%, p < 0.001). Conclusions Age-related differences exist among adults with PSC and are associated with outcomes pre- and post-transplant. Young patients may have a more robust immune-related phenotype that is associated with poorer graft survival. Future studies are needed to further investigate these findings.

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“…Whether microbial dysbiosis lowers the threshold for rejection in face transplant recipients remains to be determined. Additional factors that may have contributed to the high rate of rejection include our immunosuppression protocol with early steroid withdrawal and the younger age of the recipients (mean 37 years) and therefore a stronger immunity . Despite that, all cellular rejections were successfully treated and did not lead to graft loss.…”

Section: Discussionmentioning

confidence: 99%

Codominant Role of Interferon‐γ– and Interleukin‐17–Producing T Cells During Rejection in Full Facial Transplant Recipients

Borges

O’Malley

et al. 2016

American Journal of Transplantation

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Facial transplantation is a life-changing procedure for patients with severe composite facial defects. However, skin is the most immunogenic of all transplants, and better understanding of the immunological processes after facial transplantation is of paramount importance. Here, we describe six patients who underwent full facial transplantation at our institution, with a mean followup of 2.7 years. Seum, peripheral blood mononuclear cells, and skin biopsy specimens were collected prospectively, and a detailed characterization of their immune response (51 time points) was performed, defining 47 immune cell subsets, 24 serum cytokines, anti-HLA antibodies, and donor alloreactivity on each sample, producing 4269 data points. In a nonrejecting state, patients had a predominant T helper 2 cell phenotype in the blood. All patients developed at least one episode of acute cellular rejection, which was characterized by increases in interferon-c/interleukin-17–producing cells in peripheral blood and in the allograft’s skin. Serum monocyte chemotactic protein-1 level was significantly increased during rejection compared with prerejection time points. None of the patients developed de novo donor-specific antibodies, despite a fourfold expansion in T follicular helper cells at 1 year posttransplantation. In sum, facial transplantation is frequently complicated by a codominant interferon-γ/interleukin-17–mediated acute cellular rejection process. Despite that, medium-term outcomes are promising with no evidence of de novo donor-specific antibody development.

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Immunosenescence and Immune Response in Organ Transplantation

Cited by 38 publications

References 132 publications

Assessment of infectious complications in elderly kidney transplant recipients receiving induction with anti‐thymocyte globulin vs basiliximab

Assessment of infectious complications in elderly kidney transplant recipients receiving induction with anti‐thymocyte globulin vs basiliximab

Differences in Phenotypes and Liver Transplantation Outcomes by Age Group in Patients with Primary Sclerosing Cholangitis

Codominant Role of Interferon‐γ– and Interleukin‐17–Producing T Cells During Rejection in Full Facial Transplant Recipients

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