Role of cytokine gene polymorphism in hepatitis C recurrence and allograft rejection among liver transplant recipients.

BACKGROUND: Cytokines play a key role in the regulation of immune responses. The maximal capacity of cytokine production varies between individuals and was shown to correlate with polymorphism in cytokine gene promoters. The objective of this study was to analyze the role of cytokine allelic variations in susceptibility to early graft rejection episodes and recurrence of hepatitis C infection in liver transplant (LTx) recipients. METHODS: The genetic profile of five cytokines was studied in 68 LTx recipients and 49 controls using polymerase chain reaction sequence specific primers. All individuals were genotyped as high or low producers of TNF-alpha and IL-6 and high, intermediate, or low producers of transforming growth factor beta (TGF-beta), interferon gamma (IFN-gamma), and interleukin 10 (IL-10) based on single nucleotide substitutions. RESULTS: No statistically significant differences were observed between patients with or without early rejection episodes. A significant proportion of patients more prone to rejection were genotyped as having a low production profile of IL-10 compared with the control population (P=0.04). These data are in accordance with reports regarding other solid-organ transplant recipients. Patients with no recurrence of hepatitis C had the inherent ability to produce higher TGF-beta levels than did patients with recurrent disease (P=0.042). Among nonrecurrent patients, the percentage of genetically low IL-10 producers was higher than among recurrent patients (P=0.07). Furthermore, a genetic tendency to produce higher levels of IFN-gamma was noted among LTx recipients with nonrecurrent hepatitis C than among those with recurrent hepatitis C. CONCLUSIONS: While no significant correlation was detected between particular cytokine profile and early rejection episodes, our data strongly suggest an association between cytokine gene polymorphism of TGF-beta, IL-10, and INF-gamma and recurrence of hepatitis C in LTx recipients.

Cornea recipients: are their opinions and attitudes toward organ donation different from those of the general population?

BACKGROUND: Cornea transplantation provides a second chance for people with poor visual function. Unfortunately, there is a major shortage of donor cornea tissue. The purpose of this study was to evaluate the attitudes and willingness to donate organs among cornea transplant recipients. METHODS: Sixty-eight patients who underwent cornea transplantation between January 2002 and May 2003 were asked to complete a questionnaire dealing with their attitudes toward cornea and organ donation, and willingness to donate an organ. RESULTS: Religion was a contributing factor for a negative decision to donate organs. Only 29% of participants, most of whom were nonreligious were carrying a signed donation card. Fifty-eight percent of the patients knew that the cornea graft is derived from a deceased person; most of these patients were of European or American origin. Seventy-three percent knew that donation requires the agreement of a family member. Age, gender, marital status, and education were not significantly associated with attitude toward donation. CONCLUSION: Stronger efforts are needed by transplant coordinators, physicians, and nurses to improve the education and knowledge of patients and their families about the basic aspects of transplantation. Greater public awareness may increase the willingness to donate organs.

Extension of the organ pool in kidney transplantation: first year experience of the Israel Transplant Center.

BACKGROUND: Over a 12 month period, the Israel Transplant Center doubled the number of donors by assigning a nurse coordinator to each of 22 hospitals around the country and by using kidneys from elderly donors. OBJECTIVE: To evaluate the impact of our "marginal donors" policy on the results immediately following transplantation. METHODS: Between October 1997 and September 1998, 140 cadaveric kidney transplantations from 72 donors were performed in Israel. We defined two groups of recipients: patients with immediate graft function and patients with either delayed graft function requiring > 1 week of dialysis post-transplant or with primary graft non-function. We compared the following parameters between groups: donor and recipient age and gender, cause of donor's death, length of stay in the intensive care unit, vasopressor dosage and creatinine levels before harvesting, cold ischemic time, and the number of recipient grafts. RESULTS: There were 102 recipients (72.8%) with immediate graft function and 38 with either PNF (n = 13, 9.3%) or DGF (n = 25, 17.9%). On regression analysis, donor age > 50 year and retransplantation were significant risk factors for PNF or DGF (odds ratio 4.4 and 2.8, respectively). Of the 56 kidneys from donors > 50 years old, 21 (37.5%) developed either PNF (n = 9) or DGF (n = 12). CONCLUSIONS: We conclude that kidneys from donors over age 50 are at increased risk for graft non-function or delayed function. Better assessment of functional capacity of kidneys from "aged" donors may help to choose appropriate donors from that pool.

Allogeneic human liposomal melanoma vaccine with or without IL-2 in metastatic melanoma patients: clinical and immunobiological effects.

The aim of this pilot study was to assess the clinical and immunological effects of human allogeneic liposomal melanoma vaccine alone or combined with Interleukin-2 (IL-2) in patients with metastatic melanoma. Four concurrent treatment arms were included: vaccine alone (A); vaccine combined with systemic IL-2 (B); vaccine combined with low-dose liposomal regional IL-2 (C); and low-dose regional IL-2 as in group C but without vaccine (D). Vaccine was prepared from semisynthetic phospholipids (dimyristol phosphatidylcholine and dimyristol phosphatidylglycerol) and membranes of six human melanoma cell lines. The latter were chosen as expressing MHC class I and II antigens and a "mosaic" of melanoma-associated antigens (MAAs) as detected by MoAbs R24, p97, CF21 and TA99. Nine of the 24 patients had objective clinical responses: of the ten patients treated with liposomal vaccine and low dose regional IL-2 (arm C), three had complete responses (CR) and three had partial responses (PR); of the five patients treated with liposomal, low-dose regional liposomal IL-2 only (arm D), three had PRs. No clinical responses were seen in patients treated by vaccine alone (A) nor in patients treated by vaccine and systemic IL-2 (B). Patients' in vivo and in vitro cellular immune responses were closely monitored. Conversion to positive cutaneous delayed type hypersensitivity (DTH) to membrane vaccine (without liposomes) was induced only in the six clinical responders of arm C. Positive DTH correlated with augmented in vitro proliferative lymphocyte responses stimulated by melanoma cell lines and membrane preparation and with the augmented cytolytic activity against melanoma cell lines.