E Langhoff

Peloisis hepatis due to Bartonella henselae in transplantation : a hemato-hepato-renal syndrome

BACKGROUND Bacillary peliosis hepatis is an uncommon but well recognized disease due to disseminated Bartonella infections occurring predominantly in immunocompromised individuals infected with human immunodeficiency virus, type 1. A similar condition in the absence of Bartonella infection when described in organ transplant patients was felt to be secondary to azathioprine and/or cyclosporine. METHODS Herein, we report the first case of bacillary peliosis hepatis due to systemic Bartonella henselae infection in a patient after kidney transplant. The patient presented with severe anemia, persistent thrombocytopenia, and hepato-renal syndrome. DNA-based polymerase chain reactions (PCR), which allowed direct detection of both B henselae and quintana DNA in patients peripheral blood and liver tissue, were used. Indirect immunofluorescence assay for Bartonella serology was performed on peripheral blood. RESULTS Histopathology of the liver biopsy demonstrated peliosis hepatis. Indirect immunofluorescence assay for Bartonella serology was positive, and B henselae DNA was identified by PCR in the peripheral blood and liver tissue. Treatment with a 3-month course of oral erythromycin resulted in an excellent clinical response. CONCLUSIONS The present case suggests that although various anti-rejection therapies and opportunistic infections are associated with hepatic and renal dysfunction along with bone marrow suppression, the diagnostic evaluation in this situation should include liver biopsy and a careful search for evidence of systemic Bartonella infection, e.g., exposure to cats, Bartonella serology, and Bartonella DNA by PCR. A reduction in immunosuppression and prolonged therapy with antibiotics such as erythromycin will often result in early recovery.

In vivo and in vitro Modulation of Immune Stimulatory Capacity of Primary Dendritic Cells by Adenovirus-Mediated Gene Transduction

Dendritic cells (DCs) are potent antigen-presenting cells which are key leukocytes in the initiation of cell-mediated organ graft rejection, antiviral immunity, and antitumor responses. In this study we demonstrate that genetic modification of primary human and mouse DCs by adenoviral gene transfer is an effective means of induction and modulation of antigen presentation by DCs. An adenovirus vector (AdLacZ) was used to express an intracellular model antigen β-galactosidase (β-gal) in DCs. Our results show that 30–40% of precursor dendritic cells (PDCs) derived from human umbilical cord blood and circulating mature blood DCs express high levels β-galactosidase (β-gal) after infection with AdLacZ with no cytopathic effect observed. In vitro, AdLacZ transduced PDCs and DCs demonstrated a 10- to 20-fold higher mixed lymphocyte reaction (MLR) stimulatory capacity as compared to that of monocytes. In vivo, immunization with AdLacZ transduced mouse DCs resulted in more potent cytotoxic T lymphocyte (CTL) responses against the predicted H-2 restricted β-gal epitope as compared to CTL responses obtained by β-gal peptide pulsed DCs. Modulations of the MLR stimulatory capacity of DCs were examined by expression of mouse B7 and CTLA-4Ig. The results show that expression of mouse B7 by a recombinant adenoviral vector (Ad7) significantly enhances the MLR stimulatory capacity of human DCs. In contrast, expression of CTLA-4Ig (AdCTLA-4Ig) reduces the MLR stimulatory capacity of the transduced cells. We conclude that recombinant adenovirus can readily be used for genetic modulation DC-induced immune responses in vivo and in vitro. DCs targeted for induction of specific antigen responses or for modulation of the immune stimulatory capacity may have a potential use in the control of transplantation rejection or viral infections.

Tacrolimus/“low-dose” mycophenolate mofetil versus microemulsion cyclosporine/“low-dose” mycophenolate mofetil after kidney transplantation—1-year follow-up of a prospective, randomized clinical trial

INCE its introduction, cyclosporine, a macrolide molecule that inhibits expression of interleukin-2 by lymphocytes, when administered prophylactically in combination with corticosteroids and/or azathioprine, has dramatically improved results of solid organ transplantation. 1 Recently, microemulsion formulation of cyclosporine (Neoral), when compared with CsA, was found to provide better immunosuppression, primarily due to improvement in drug bioavailability. 2 In a multicenter clinical trial, tacrolimus (FK 506), another macrolide molecule with mode of action similar to CsA, was found to be more effective than CsA in the prevention of rejection in renal transplant recipients. 3 Mycophenolate mofetil (MMF), the morpholinoethylester of mycophenolic acid, is an uncompetitive, reversible inhibitor of eukaryotic inosine monophosphate dehydrogenase, a key enzyme in the de novo pathway of purine synthesis during lymphocyte proliferation. 4 In European, tricontinental, and American multicenter clinical trials, MMF in 2- and 3-g doses, when compared with azathioprine/placebo, significantly reduced the incidence of acute rejection in renal transplant recipients. 5‐7

A comparative study of 500 mg BID and 250 mg BID of prophylactic oral ganciclovir in post–kidney transplant “CMV at risk” recipients

HUMAN cytomegalovirus (CMV) is a ubiquitous pathogen that is the major cause of morbidity and mortality in immunocompromised individuals, such as organ transplant recipients. As many as 70%–80% of recipients of solid organ transplants show evidence of CMV infection. It is well recognized that the incidence of posttransplant CMV infection depends on various factors including overall immunosuppression, underlying CMV status of both donor and recipients, and antiviral prophylaxis. Recently, we reported on the effectiveness of an oral formulation of ganciclovir in reducing CMV infection in kidney transplant recipients. This study prospectively examines the efficacy of two different regimens of oral ganciclovir in microemulsion cyclosporine/“low-dose” mycophenolate mofetil (MMF)-treated renal transplant patients.