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Long-term Immunosuppression (long-term + immunosuppression)

Distribution by Scientific Domains

Medical Sciences	87%

Distribution within Medical Sciences

Transplantation	57%
Dermatology	28%

Selected Abstracts

Dendritic Cell Deficiency in the Blood of Kidney Transplant Patients on Long-Term Immunosuppression: Results of a Prospective Matched-Cohort Study

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005
Holger Hackstein
Evidence from in vitro studies suggests that immunosuppressive drugs interfere with key functions of dendritic cells (DCs), but the in vivo relevance of these findings is elusive. We prospectively analyzed the major DC precursor subsets in the blood of kidney transplant recipients on long-term immunosuppression (,1 year). A total of 87 patients were compared to 87 age- and sex-matched controls. Total DC numbers and the precursor subsets, myeloid type 1 DCs, myeloid type 2 DCs (mDC1, mDC2) and plasmacytoid DCs (pDCs) were identified by four color flow cytometry. Long-term immunosuppression was associated with significant reduction of all major DC subsets in comparison to healthy controls (mDC1 p < 0.001; mDC2 p < 0.0001; two-tailed Mann-Whitney U -test) with the strongest negative impact on pDCs (p < 0.00001). In contrast, total leukocyte numbers were not significantly affected. Analysis of the relative impact of different agents revealed a significant impact of prednisolone on pDCs (p = 0.009) and mDCs2 (p = 0.006). The functional relevance of pDC deficiency was confirmed independently by Interferon-alpha analysis after Toll-like receptor 7 (p , 0.001) and 9 (p < 0.05) stimulation. These results indicate for the first time a profound negative impact of long-term immunosuppression on major DC subsets in kidney transplant recipients. DC deficiency may have important implications with respect to viral infections and tumor development. [source]

Dietary exposure to low pesticide doses causes long-term immunosuppression in the leopard frog (Rana pipiens)

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2007
Anathea Albert
Abstract This study examines the relationship between dietary exposure of pesticides, DDT, and dieldrin and immunosuppression in the northern leopard frog (Rana pipiens). Immune function was measured before, during, and after a 10-week exposure period with the use of both adaptive and innate immunity responses. Exposure to low doses (75 ng/g body wt DDT or 2.1 ng/g dieldrin total dose over the 10 weeks) resulted in significant suppressive effects on antibody production and secondary delayed-type hypersensitivity (DTH). The high doses (750 ng/g DDT and 21 ng/g dieldrin), however, did not affect antibody production, DTH, or oxidative burst in a predictable dose,response manner. The differences in magnitude and direction of the effects of the two dosing regimes were likely due to differences in chemical exposure on the basis of feeding and effectiveness of chemical uptake. The low dose results demonstrated that moderate concentrations of pesticides, frequently observed in the environment, are able to weaken the immune response of R. pipiens. [source]

Production and clearance of cyclobutane dipyrimidine dimers in UV-irradiated skin pretreated with 1% pimecrolimus or 0.1% triamcinolone acetonide creams in normal and atopic patients

EXPERIMENTAL DERMATOLOGY, Issue 5 2006
Laurence Doelker
Background:, Ultraviolet (UV)-induced pyrimidine dimers are an early step in skin carcinogenesis, which is accelerated in the setting of long-term immunosuppression with systemic calcineurin inhibitors. It is not known whether topical application of calcineurin inhibitors exposes to a similar risk. Objective:, To assess the formation and clearance of UV-induced dipyrimidine dimers in human epidermis treated with topical pimecrolimus as compared to topical steroid, vehicle and untreated control. Methods:, Pretreated buttock skin of 20 human volunteers with (10) or without (10) atopic dermatitis was exposed to two minimal erythema doses (MED) of simulated solar radiation. DNA was extracted from epidermis 1 and 24 h postirradiation. Pyrimidine dimers were visualized by immuno slot blots and quantified by chemoluminescence image analysis. Results:, One-hour postirradiation, pimecrolimus-treated epidermis contains less DNA damage as compared to untreated control, but there were no statistically significant differences between pimecrolimus, triamcinolone acetonide and vehicle. Dimer levels at 24 h postirradiation showed no significant differences between different treatments. Conclusion:, Treatment with pimecrolimus cream, triamcinolone acetonide cream and vehicle is not associated with increased epidermal DNA damage at 1 and 24 h post-UV exposure. [source]

The mechanisms underlying MMR deficiency in immunodeficiency-related non-Hodgkin lymphomas are different from those in other sporadic microsatellite instable neoplasms

INTERNATIONAL JOURNAL OF CANCER, Issue 10 2009
Claire Borie
Abstract The spectrum of tumors showing microsatellite instability (MSI) has recently been enlarged to sporadic neoplasms whose incidence is favored in the context of chronic immunosuppression. We investigated the biological, therapeutic and clinical features associated with MSI in immunodeficiency-related non-Hodgkin lymphomas (ID-RL). MSI screening was performed in 275 ID-RL. MSI ID-RL were further analyzed for MMR gene expression and for BRAF/KRAS mutations since these genes are frequently altered in MSI cancers. We also assessed the expression of O6 -methylguanine-DNA methyltransferase (MGMT), an enzyme whose inactivation has been reported in lymphomas and may help in the selection of MMR deficient clones. Unlike other sporadic MSI neoplasms, MSI ID-RL (N = 17) presented with heterogeneous MMR defects and no MLH1 promoter methylation. About one third of these tumors presented with normal expression of MLH1, MSH2, MSH6 and PMS2. They accumulated BRAF activating mutations (33%). Unlike other ID-RL, MSI ID-RL were primarily EBV-negative NHL of T-cell origin, and arose after long-term immunosuppression in patients who received azathioprine as part of their immunosuppressive regimen (p = 0.05) and/or who exhibited methylation-induced loss of expression of MGMT in tumor cells (p= 0.02). Overall, these results highlight that, in the context of deficient immune status, some MSI neoplasms arise through alternative mechanism when compared to other sporadic MSI neoplasms. They give the exact way how to make the diagnosis of MSI in these tumors and may help to define biological and clinicalrisk factors associated with their emergence in such a clinicalcontext. © 2009 UICC [source]

Recurrent autoimmune hepatitis after liver transplantation: Diagnostic criteria, risk factors, and outcome

LIVER TRANSPLANTATION, Issue 4 2001
Stefan G. Hübscher MD
Approximately 20% to 30% of patients undergoing liver transplantation for autoimmune hepatitis (AIH) develop features of recurrent disease. Diagnostic criteria for recurrent AIH are similar to those used in the nontransplanted liver and include, in varying combinations, biochemical, serological, and histological abnormalities and steroid dependency. However, these criteria are more difficult to apply in the liver allograft because of potential interactions between recurrent AIH and other complications of liver transplantation, particularly rejection, and the uncertain effects of long-term immunosuppression. In the absence of other reliable diagnostic markers, a number of studies have used the histological finding of chronic hepatitis as the main or sole criterion for diagnosing recurrent AIH. However, this also lacks diagnostic specificity because there are many other possible causes of chronic hepatitis in the liver allograft. In addition, approximately 20% to 40% of biopsies performed on patients as part of routine annual review have histological features of chronic hepatitis, for which no definite cause can be identified. Risk factors that have been associated with the development of recurrent AIH include suboptimal immunosuppression, HLA phenotype, disease type and severity in the native liver, and duration of follow up. In many cases in which recurrent AIH seems to be related to underimmunosuppression, biochemical and histological features rapidly resolve once adequate immunosuppression is restored. However, in other cases, recurrent AIH behaves more aggressively, with progression to cirrhosis and graft failure. Areas that require further study include developing uniform criteria for the diagnosis of recurrent AIH, identifying risk factors for severe recurrent disease, and determining optimal levels of immunosuppression that minimize the impact of disease recurrence without exposing patients to the risks of overimmunosuppression. [source]

Dendritic Cell Deficiency in the Blood of Kidney Transplant Patients on Long-Term Immunosuppression: Results of a Prospective Matched-Cohort Study

Antiepiligrin (laminin 5) cicatricial pemphigoid complicated and exacerbated by herpes simplex virus type 2 infection

AUSTRALASIAN JOURNAL OF DERMATOLOGY, Issue 4 2001
Tanya K Gilmour
SUMMARY A 50-year-old man with antiepiligrin (laminin 5) cicatricial pemphigoid (AeCP) involving the eyes, mouth and skin required a combination of systemic drug therapies to suppress the ocular disease. Herpes simplex virus type 2 infection of the mouth and pharynx precipitated an acute deterioration, with laryngeal involvement and an increase in oral ulceration. This is an unusual complication of long-term immunosuppression and illustrates some of the difficulties in the management of patients with AeCP. Clinical improvement was obtained with oral antiviral therapy and adjustment of his immunosuppressive regimen. [source]