Cell-mediated immune response to influenza vaccination in lung transplant recipients.

BACKGROUND: Lung transplant recipients are susceptible to complications from influenza infection. Antibody responses to influenza vaccination have been shown to be decreased in lung transplant recipients. Cellular immune mechanisms serve an important role in influenza clearance. The cellular immune response to influenza vaccination has not been studied in transplant populations. METHODS: Interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels to the three viral antigens included in the 1999 to 2000 influenza vaccine were measured before and 4 weeks post-vaccination in 43 lung transplant recipients and 21 healthy adult controls. RESULTS: Interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels did not increase from pre- to post-vaccination in the lung transplant group. Both pre- and post-cytokine levels were lower in the transplant group compared to the control group. Pre- and post-granzyme B levels did not differ significantly between the groups. The T-helper response in the control group varied with the different viral strains. A correlation between acute rejection episodes and the absence of both azathioprine and mycophenolate was found. CONCLUSIONS: Influenza vaccination does not stimulate a cell-mediated immune response in lung transplant recipients as judged by interleukin-2, interleukin-10, interferon-gamma, and granzyme B levels. Alternative prevention strategies may be needed.     

Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs

Salles MJC, Sens YAS, Boas LSV, Machado CM. Influenza virus vaccination in kidney transplant recipients: serum antibody response to different immunosuppressive drugs.
Clin Transplant 2010: 24: E17–E23. © 2009 John Wiley & Sons A/S.   Abstract: 
Introduction:  This study prospectively accessed the immune response to the inactivated influenza vaccine in renal transplant recipients receiving either azathioprine or mycophenolate mofetil (MMF). Side effects were investigated.
Methods:  Sixty-nine patients received one dose of inactivated trivalent influenza vaccine. Antihemagglutinin (HI) antibody response against each strain was measured before and one to six months after vaccination.
Results:  Geometric mean HI antibody titers for H1N1 and H3N2 strains increased from 2.57 and 2.44 to 13.45 (p = 0.001) and 7.20 (p < 0.001), respectively. Pre- and post-vaccination protection rates for H1N1 and H3N2 increased from 8.7% to 49.3% (p < 0.001); and 36.3% (p < 0.001) and seroconversion rates were 36% and 25.3%, respectively. There was no response to influenza B. The use of MMF reduced the H1N1 and H3N2 protection rates and the seroconversion rate for the H1N1 strain when compared with the use of azathioprine, and subjects transplanted less than 87 months also had inferior antibody response. Adverse events were mild and there were no change on renal function post-vaccination.
Conclusion:  Renal transplant patients vaccinated against influenza responded with antibody production for influenza A virus strains, but not for influenza B. Use of MMF and shorter time from transplantation decreased the immune response to the vaccine.     

Influenza Vaccination in Orthotopic Liver Transplant Recipients: Absence of Post Administration ALT Elevation

Influenza vaccination has reduced life-threatening complications from influenza virus infection in adult liver transplant recipients. We evaluated changes in aminotransferase level and immunogenicity of influenza vaccination in liver transplant recipients. Fifty-one liver transplant recipients were administered a standard dose of the 2002-2003 inactivated trivalent influenza vaccine. ALT values were measured at baseline, 1 week and 4-6 weeks postvaccination. Antibody responses to each component of the vaccine were measured at baseline and after 4-6 weeks by a hemagglutination inhibition (HAI) assay. Response was defined as an HAI titer > or = 1: 40 and/or a 4-fold increase in antibody titers from baseline. An ALT elevation was defined as a rise of > or = 50% from baseline. There was no difference in the median rise in ALT value between seroconverters and nonseroconverters. A significant number of recipients developed potentially protective antibody titers (p-value < 0.0001). At less than 4 months post transplantation, 1/7 (14%), at 4-12 months, 6/9 (67%), and after 12 months, 30/35 (86%) subjects responded to the H1 strain. Of 51 recipients, one HCV (-) recipients vaccinated within 3 months of transplantation developed acute cellular rejection. Influenza virus vaccination is not associated with allograft rejection or ALT flares in liver transplant recipients.     

Heterologous Immune Responses to Influenza Vaccine in Kidney Transplant Recipients

Influenza vaccine is known to have suboptimal immunogenicity in transplant recipients. Despite this, influenza vaccine may have the added benefit of inducing a cross‐reactive immune response to viral strains not found in the vaccine. This is termed “heterologous immunity” and has not been assessed previously in transplant patients. Pre‐ and postvaccination sera from kidney transplant recipients (n = 60) immunized with the 2012–2013 adjuvanted or nonadjuvanted influenza vaccine underwent testing by hemagglutination inhibition assay for strains not present in vaccine: A/New Caledonia/20/99 (H1N1), A/Texas/50/2012 (H3N2) and B/Brisbane/60/2008. The geometric mean titer of antibody to heterologous strains increased after vaccine (H1N1: 80.0 to 136.1, p < 0.001; H3N2: 23.3 to 77.3, p < 0.001; B: 13.3 to 19.5, p < 0.001). Seroconversion rates were 16.7%, 41.7%, and 13.3%, respectively. No differences in heterologous response were seen in the adjuvanted versus nonadjuvanted groups. Patients were more likely to seroconvert for a cross‐reactive antigen if they seroconverted for the specific vaccine antigen. Seroconversion to heterologous A/H3N2, for example, was 84.0% for homologous H3N2 seroconverters versus 11.4% for nonseroconverters (p < 0.001). This study provides novel evidence that transplant recipients are able to mount significant cross‐protective responses to influenza vaccine that may be an additional, previously unknown benefit of immunization.     

Mycophenolate and lower graft function reduce the seroresponse of kidney transplant recipients to pandemic H1N1 vaccination

In late 2009 transplant organizations recommended that kidney recipients be vaccinated for pandemic H1N1 influenza (pH1N1); however, the vaccine efficacy was unknown. We had offered a monovalent non-adjuvanted pH1N1 vaccine to transplant recipients. Here we compared the pre- and post-vaccination seroresponses of 151 transplant recipients to that of 71 hemodialysis patients and 30 healthy controls. Baseline seroprotection was similar between groups but was significantly different at 1 month (44, 56, and 87%, respectively). Seroconversion was significantly less common for transplant recipients (32%) than dialysis patients (45%) and healthy controls (77%). After adjusting for age and gender, dialysis patients were significantly more likely (2.7-fold) to achieve new seroprotection than transplant recipients. The likelihood of seroprotection in transplant recipients was significantly reduced by mycophenolate use (adjusted odds ratio 0.24), in a dose-dependent manner, and by reduced eGFR (adjusted odds ratio 0.16 for worst to best). Seroprotection and geometric mean antibody titers increased substantially in 49 transplant recipients who subsequently received the 2010 seasonal influenza vaccine. Thus, patients requiring renal replacement therapy had reduced seroresponses to vaccination with the monovalent vaccine compared with healthy controls. Transplant recipient responses were further reduced if they were receiving mycophenolate or had significantly lower graft function.     

The antibody response to pandemic H1N1 2009 influenza vaccine in adult organ transplant patients

Limited data are available regarding antibody response and the safety of the monovalent influenza A H1N1/09 vaccine for immunocompromised patients. In this study, the humoral response to this vaccine in solid organ transplant (SOT) recipients and healthy individuals was evaluated. Eighty‐two SOT recipients and 28 healthy individuals received two doses of the influenza A H1N1/09 AS03 adjuvanted vaccine containing 3.75 mg of haemagglutinin at a 3‐ to 4‐week interval. Serum samples were drawn at baseline and 3–4 weeks after the first and second vaccine doses. Seroprotective titres were measured with a haemagglutination inhibition. After the first dose seroprotective titres were observed in 69% of the SOT patients and in 96% of the healthy controls (P = 0.006), and increased after the second dose to 80% and 100%, respectively (P = 0.003). All controls and 77% of the SOT recipients achieved a ≥4‐fold titre rise after the first immunisation (P = 0.005). The vaccine was well tolerated and no acute rejection was observed. Influenza A H1N1/09 vaccine elicited a protective antibody response in the majority of SOT recipients, but the response was lower when compared with controls. A second dose significantly improved vaccine immunogenicity in SOT recipients. (ClinicalTrials.gov number: NCT01254955)     

Outcomes of African American kidney transplant recipients treated with sirolimus,tacrolimus, and corticosteroids

BACKGROUND: African American kidney transplant recipients generally exhibit poor long-term graft survival compared with other ethnic groups. The combination of sirolimus, tacrolimus, and corticosteroids has proven to be effective in reducing rejection episodes in high-risk organ and islet cell transplant recipients but has not yet been tested in a large number of African American patients. METHODS: The outcomes of 56 African American adult, primary kidney transplant recipients treated with corticosteroids, sirolimus, and tacrolimus targeted to relatively low trough blood levels were compared with those of a concurrent group of 65 white patients treated with steroids, mycophenolate mofetil, and tacrolimus targeted to relatively high blood levels. Induction antibody therapy was not routinely used in either group. RESULTS: The incidence of acute rejection in the first 3 posttransplantation months was 7.1% in African Americans and 16.9% in whites (P=NS). Actuarial 2-year patient, graft, and rejection-free graft survival rates were equivalent in the two groups. Posttransplantation diabetes mellitus occurred in 36% of the African American patients, despite similar doses of corticosteroids and lower trough levels of tacrolimus, compared with 15% of white patients (P=0.024). CONCLUSIONS: The combination of corticosteroids, sirolimus, and relatively low doses of tacrolimus results in acute rejection, graft survival, and patient survival rates equivalent to those achieved in white patients receiving steroids, mycophenolate mofetil, and relatively high doses of tacrolimus, even without the routine use of induction antibody therapy. Posttransplantation diabetes mellitus remains a problem for African Americans receiving this combination of immunosuppressants, despite relatively low tacrolimus blood levels.     

Serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine in lung transplant recipients

Lung transplant recipients have an increased risk for severe coronavirus disease 2019 (COVID-19) due to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A third dose of a SARS-CoV-2 vaccine has been recommended for all solid organ transplant recipients, but data from lung transplant recipients specifically are scarce. In this study, the serologic response to a third dose of an mRNA-based SARS-CoV-2 vaccine was measured in 78 lung transplant recipients. Sixty-two percent (n = 48) had a serological response to vaccination, which was significantly higher than after the second vaccine dose (27 patients (35%); p = 0.0013). A positive serologic response was associated with having had COVID-19 (p = 0.01), and higher serum IgG level and complement mannose binding lectin pathway activity prior to vaccination (p = 0.04 and p = 0.03, respectively). Serologic response was not associated with the dose of mycophenolate mofetil or prednisone or other immune status parameters. Eleven patients (14%) developed COVID-19 after the second or third vaccine dose, but this did not associate with serologic response after the second vaccine dose (9% in patients who developed COVID-19 versus 39% in patients who did not develop COVID-19 (p = 0.09)), or with serologic response above cut-off values associated with clinical protection in previous studies. In conclusion, the response to mRNA-based SARS-CoV-2 vaccines in lung transplant recipients improves significantly after a third vaccine dose. Factors associated with a positive serologic response are having had COVID-19 prior to vaccination, and serum IgG and complement mannose binding lectin pathway activity prior to vaccination. Serologic response did not associate with clinical protection against COVID-19 in this study.     

Impairment of the immune response to influenza vaccination in renal transplant recipients by cyclosporine, but not azathioprine

Influenza vaccination has been strongly recommended for immunosuppressed renal transplant recipients. However, immunosuppression may lead to impaired antibody responses. We studied the antibody response to an inactivated trivalent influenza vaccine in 59 renal transplant recipients with life-sustaining kidney function: 21 were on cyclosporine and prednisone, 38 on azathioprine and prednisone. Healthy volunteers (n = 29) and patients on hemodialysis (n = 28) served as controls. Despite comparable renal allograft function, cyclosporine-treated patients had a significantly lower immune response against influenza A viruses than azathioprine-treated patients, whether mean antibody levels, fourfold titer rise, or seroconversion to protective titers was analyzed. No significant differences in antibody responses were found between healthy controls and patients on azathioprine. The patients on hemodialysis showed an impaired response to vaccination. However, in contrast to the cyclosporine-treated patients, booster immunization proved valuable in this group.     

Seasonal Maintenance of Influenza Vaccine-Induced Antibody Response in Kidney Transplant Recipients

Background/Aims: Although annual influenza vaccination is recommended for kidney transplant recipients, efficacy as reflected by serum antibody titers has not been well studied beyond 1 month in kidney transplant recipients. Methods: We performed a single-center prospective cohort study of 51 kidney transplant recipients and 102 healthy controls receiving the 2006-2007 influenza vaccine. Anti-hemagglutinin antibody titers to A/H1N1, A/H3N2, and B were measured before and 1 month after vaccination, and again at the end of influenza season. The primary outcome was the proportion of participants maintaining seroprotection (antibody titer ≥1:32) for the duration of the influenza season after influenza vaccination. Results: Median follow-up time was 175 and 155 days in the transplant and control groups, respectively. For types A/H1N1 and B, a similar high proportion of the transplant and control groups (88.5 and 81.6% vs. 83.7 and 74.2% for A/H1N1 and B, respectively) maintained seroprotection. For type A/H3N2, significantly less of the transplant group (66.7%) versus the control group (90%) maintained a protective influenza vaccine response (odds ratio 0.21, 95% confidence interval 0.07-0.64). This difference disappeared in adjusted analyses. Actual geometric mean titers decreased significantly within both groups (p < 0.001) but this did not differ between groups. Conclusions: Once they have developed protective vaccine-induced antibody responses to influenza vaccine, kidney transplant recipients are able to maintain adequate protective levels of antibody compared with healthy controls.     

Influenza Vaccination Is Efficacious and Safe in Renal Transplant Recipients

Whether influenza vaccination in solid-organ transplant recipients is efficacious remains a controversial issue. Furthermore, theoretical concerns have been raised regarding the safety of vaccination as it might trigger rejection of the allograft. The present prospective trial is aimed at investigating the antibody response and safety of influenza vaccination in renal transplant recipients (RTR).
A total of 165 RTR and 41 healthy volunteers were vaccinated with a standard trivalent inactivated influenza vaccine. Hemagglutination-inhibiting (HI) antibodies were quantified before and 1 month after vaccination. Seroprotection (SP) and seroresponse (SR) were defined as a titer ≥40 and a 4-fold rise in HI titer, respectively. Similar SR rates were observed in both groups. Postvaccination SP rates in RTR amounted to 92.7%, 78.7% and 82.9% for A/H1N1, A/H3N2 and B, respectively. High baseline SP rates, most probably reflecting frequent preimmunizations, explain partly the high postvaccination SP rates. SR rate was independently and inversely associated with baseline SP rate. Mycophenolate mofetil ( MMF ) usage was associated with a 2.6–5-fold lower SR. Nonetheless, these patients showed good postvaccination SP rates. A booster dose did not enhance SP or SR rates. Influenza vaccination neither affected allograft function nor caused rejection episodes. In conclusion, influenza vaccination is efficacious and safe in renal transplantation.     

A pilot protocol of a calcineurin-inhibitor free regimen for kidney transplant recipients of marginal donor kidneys or with delayed graft function

Abstract: Background: The worsening shortage of cadaver donor kidneys has prompted use of expanded or marginal donor kidneys (MDK), i.e. older age or donor history of hypertension or diabetes. MDK may be especially susceptible to calcineurin-inhibitor (CI) mediated vasoconstriction and nephrotoxicity. Similarly, early use of CI in patients with delayed graft function may prolong ischaemic injury. We developed a CI-free protocol of antibody induction, sirolimus, mycophenolate mofetil, and prednisone in recipients with MDK or DGF.
Methods: Adult renal transplant recipients who received MDK or had DGF were treated with a CI-free protocol consisting of antibody induction (basiliximab or thymoglobulin), sirolimus, mycophenolate mofetil, and prednisone. Serial biopsies were performed for persistent DGF. Patients were followed prospectively with the primary endpoints being patient and graft survival, biopsy-proven acute rejection, and sirolimus-related toxicity.
Results: Nineteen recipients were treated. Mean follow-up was 294 days. Actuarial 6- and 12-month patient survival was 100% and 100% and graft survival was 93% and 93%, respectively. The only graft loss was due to primary non-function (PNF). The incidence of AR was 16%. Mean serum creatinine at last follow-up was 1.6 mg/dL. Sirolimus-related toxicity included lymphocele (1), wound infection (2), thrombocytopenia (1) and interstitial pneumonitis (1).
Conclusion: A CI-free protocol with antibody induction and sirolimus results in low rates of AR and PNF and excellent early patient and graft survival in patients with MDK and DGF. CI-free protocols may allow expansion of the kidney donor pool by encouraging utilization of MDK at high risk for DGF or CI-mediated nephrotoxicity.     

The Effect of Sirolimus Therapy on Vaccine Responses in Transplant Recipients

Different immunosuppressant regimens vary in their effects on antibody responses to vaccination. The combination of prednisolone and azathioprine has only a minor effect, whereas the addition of ciclosporin attenuates protective antibody responses to influenza vaccination. The effect of sirolimus, a new immunosuppressant, on vaccine responses has been little studied. Thirty-two hepatic or renal transplant patients randomized to calcineurin inhibitor-based or sirolimus-based immunosuppression were vaccinated against influenza and pneumococcus. Following tri-valent influenza vaccination, a similar rise in antibody titer occurred in sirolimus and calcineurin inhibitor (CNI) treated patients, though sirolimus treated patients developed a 'protective' titer to more influenza antigens. The pneumococcal polysaccharide vaccine was equally effective in both groups. Hence, vaccination guidelines in place for CNI treated patients are likely to be appropriate for transplant recipients maintained on sirolimus.     

Randomized Controlled Trial of High‐Dose Intradermal Versus Standard‐Dose Intramuscular Influenza Vaccine in Organ Transplant Recipients

The immunogenicity of standard intramuscular (IM) influenza vaccine is suboptimal in transplant recipients. Also, recent studies suggest that alloantibody may be upregulated due to vaccination. We evaluated a novel high‐dose intradermal (ID) vaccine strategy. In conjunction, we assessed alloimmunity. Transplant recipients were randomized to receive IM or high‐dose ID vaccine. Strain‐specific serology and HLA alloantibody production was determined pre‐ and postimmunization. In 212 evaluable patients (105 IM, 107 ID), seroprotection to H1N1, H3N2 and B strains was 70.5%, 63.8% and 52.4% in the IM group, and 71.0%, 70.1%, 63.6% in the ID group (p = ns). Seroconversion to ≥1 antigen was 46.7% and 51.4% in the IM and ID groups respectively (p = 0.49). Response was more likely in those ≥6 months posttransplant (53.2% vs. 19.2%; p = 0.001). Use of mycophenolate mofetil was inversely associated with vaccine response in a dose‐dependent manner (p < 0.001). Certain organ subgroups had higher response rates for influenza B in the ID vaccine group. Differences in anti‐HLA antibody production were detected in only 3/212(1.4%) patients with no clinical consequences. High‐dose intradermal vaccine is an alternative to standard vaccine and has potential enhanced immunogenicity in certain subgroups. In this large cohort, we also show that seasonal influenza does not result in significant alloantibody production.     

Immunogenicity and Safety of an Intradermal Boosting Strategy for Vaccination Against Influenza in Lung Transplant Recipients

The immunogenicity of influenza vaccine is suboptimal in lung transplant recipients. Use of a booster dose and vaccine delivery by the intradermal rather than intramuscular route may improve response. We prospectively evaluated the immunogenicity and safety of a 2-dose boosting strategy of influenza vaccine. Sixty lung transplant recipients received a standard intramuscular injection of the 2006-2007 inactivated influenza vaccine, followed 4 weeks later by an intradermal booster of the same vaccine. Immunogenicity was assessed by measurement of geometric mean titer of antibodies after both the intramuscular injection and the intradermal booster. Vaccine response was defined as 4-fold or higher increase of antibody titers to at least one vaccine antigen. Thirty-eight out of 60 patients (63%) had a response after intramuscular vaccination. Geometric mean titers increased for all three vaccine antigens following the first dose (p < 0.001). However, no significant increases in titer were observed after the booster dose for all three antigens. Among nonresponders, 3/22 (13.6%) additional patients responded after the intradermal booster (p = 0.14). The use of basiliximab was associated with a positive response (p = 0.024). After a single standard dose of influenza vaccine, a booster dose given by intradermal injection did not significantly improve vaccine immunogenicity in lung transplant recipients.     

Oral ulcers in kidney transplant recipients treated with sirolimus and mycophenolate mofetil

BACKGROUND: In an attempt to reduce calcineurin inhibitor toxicity, transplant patients treated with tacrolimus can be switched to maintenance treatment with sirolimus. METHODS: In a prospective, randomized, multicenter trial, 33 kidney transplant recipients on steroid-free maintenance treatment with tacrolimus and mycophenolate mofetil continued tacrolimus and mycophenolate mofetil (control group, n=18) or were converted from tacrolimus to sirolimus (study group, n=15) at 1 year after transplantation. RESULTS: The study was prematurely stopped as a result of a cluster of nine patients suffering from painful oral ulcerations in the study group. Oral ulcerations did not occur in the control group. The authors here report on the individual cases suffering from this side effect of the instituted immunosuppressive regimen. CONCLUSIONS: The authors review the literature with respect to the occurrence of oral ulcers associated with the use of sirolimus or mycophenolate mofetil and speculate on the causes of the high incidence of oral ulcers in their study group. Possible explanations are overimmunosuppression during the period of the conversion from tacrolimus to sirolimus without antiviral prophylaxis, the use of the oral emulsion instead of tablets, or the lack of corticosteroid co-administration.     

De novo immunosuppression with sirolimus and tacrolimus in heart transplant recipients compared with cyclosporine and mycophenolate mofetil: a one-year follow-up analysis

BACKGROUND: Limited data exist regarding the safety and efficacy of sirolimus in combination with a calcineurin inhibitor in heart transplant recipients. METHODS: From January 2001 to June 2002, 31 de novo heart transplant recipients (treatment group) received a combination of sirolimus, tacrolimus, low-dose rabbit antithymocyte globulin, and glucocorticoids. Outcomes, such as actuarial survival, rate of rejection, incidence of infection, probability of developing diabetes mellitus, renal function, platelet and white blood cell counts, and incidence of coronary artery disease at 1 year, were compared with a cohort of 25 patients (control group) who underwent transplantation primarily in 2000 and in early 2002 treated with cyclosporine, mycophenolate mofetil, and glucocorticoids. All patients were followed up for at least 12 months. RESULTS: Kaplan-Meier actuarial 1-year survival rates were equivalent between groups (97% for the treatment group and 88% for the control group), as was freedom from allograft rejection (48% and 42% for treatment and control groups, respectively). No cases of transplant arteriopathy were noted within the first posttransplantation year. Renal function was not significantly affected in either group. There was a striking increased incidence of mediastinitis in the treatment group (19%) versus 0% in the control group (P = .02). Tacrolimus-sirolimus therapy was associated with a nearly 11-fold increased incidence of new-onset diabetes mellitus as well (P = .004). CONCLUSION: Tacrolimus, sirolimus, and steroids (following low-dose rabbit antithymocyte globulin) were associated with an increased incidence of mediastinitis and posttransplantation diabetes mellitus. No obvious long-term benefit on survival, arteriopathy, or renal function was noted.     

Initial single-center experience with sirolimus after lung transplantation

BACKGROUND: Standard immunosuppression after lung transplantation includes calcineurin inhibitors, mycophenolate mofetil, and steroids. Long-term survivors of lung transplantation are often confronted with chronic kidney disease, by definition related to the intake of calcineurin inhibitors. Sirolimus has been increasingly proposed as an alternative immunosuppressive agent due to its absence of nephrotoxicity, which could be used in selected patients. METHODS: We prospectively administered sirolimus as an alternative to calcineurin inhibitors in 10 lung transplantation recipients with persistent drug nephrotoxicity. They were switched from tacrolimus to sirolimus. Four patients also had bronchiolitis obliterans syndrome. The conversion scheme consisted of an immediate stop of tacrolimus and an 6 to 8-mg loading dose of sirolimus, followed by 4 mg/d. After 5 days, the sirolimus dose was adjusted to maintain trough levels between 12 and 18 ng/mL or 6 and 12 ng/mL for combined sirolimus and tacrolimus. Patients were monitored for renal and graft function as well as clinical status. RESULTS: A significant decrease in creatinine was observed after 1 week of treatment (P = .011). Azotemia decreased after 1 month, remaining stable (P < .01). Pulmonary function tests did not show significant modification from before sirolimus, inception in patients with or without bronchiolitis obliterans syndrome. There were seven infections. One patient died of complications related to bronchiolitis obliterans. CONCLUSION: Sirolimus was a useful alternative immunosuppressant, allowing significant tacrolimus withdrawal in transplant recipients with renal impairment. Sirolimus administration allowed recovery of renal function with low morbidity; it was useful for rescue of chronic renal impairment after lung transplantation.     

Humoral response to natural influenza infection in solid organ transplant recipients

The humoral immune response of transplant recipients to influenza vaccination has been studied in detail. In contrast, the hemagglutinin inhibiting (HI) antibody response evoked by natural influenza infection and its impact on viral kinetics is unknown. In this prospective, multicenter, cohort study of natural influenza infection in transplant recipients, we measured HI antibody titers at presentation and 4 weeks later. Serial nasopharyngeal viral loads were determined using a quantitative influenza A polymerase chain reaction (PCR). We analyzed 196 transplant recipients with influenza infection. In the cohort of organ transplant patients with influenza A (n = 116), seropositivity rates for strain‐specific antibodies were 44.0% (95% confidence interval [CI] 31.5‐53.2%) at diagnosis and 64.7% (95% CI 55.4‐72.9%) 4 weeks postinfection. Seroconversion was observed in 32.8% (95% CI 24.7‐41.9%) of the cases. Lung transplant recipients were more likely to seroconvert (P = .002) and vaccine recipients were less likely to seroconvert (P = .024). A subset of patients (n = 30) who were unresponsive to prior vaccination were also unresponsive to natural infection. There was no correlation between viral kinetics and antibody response. This study provides novel data on the seroresponse to influenza infection in transplant patients and its relationship to a number of parameters including a prior vaccination status, virologic measures, and clinical variables.     

Impact of immunosuppressive regimen on survival of kidney transplant recipients with hepatitis C

BACKGROUND: Hepatitis C virus (HCV) infection is common among end-stage renal disease patients receiving hemodialysis and a kidney transplant. HCV-positive kidney transplant recipients have worse clinical outcomes than those who are HCV negative. The optimal immunosuppressive regimen in this group of patients remains uncertain. METHODS: Using data obtained from the Organ Procurement and Transplantation Network/Scientific Registry of Transplant Recipients, we studied the impact of induction and maintenance immunosuppression on risk of patient death, with death-censored graft failure and death with a functioning graft as secondary endpoints. Cox regression analysis was used to estimate hazard ratios (HR) adjusted for donor, recipient, and transplant variables. A total of 3708 HCV-positive and 75,629 HCV-negative kidney transplant recipients were analyzed. RESULTS: Patient survival was negatively affected by HCV-positive serology. Among HCV-positive kidney transplant recipients, a reduced HR for patient death was observed with the use of induction therapy (HR=0.75, 95% CI 0.61-0.90, P=0.003) and with the use of mycophenolate mofetil (HR=0.77, 95% CI 0.64-0.92, P=0.005). CONCLUSIONS: In kidney transplant recipients with HCV-positive serology, the use of antibody induction did not negatively affect patient survival and the use of mycophenolate mofetil as part of maintenance immunosuppression was associated with better patient survival.