Research Highlights

Abstract

Melanoma Risk and Survival Among Organ Transplant Recipients. Robbins HA, Clarke CA, and Arron ST, et al. J Invest Dermatol. 13 August 2015 The risk of melanoma in solid organ transplant recipients is significantly increased compared to nonimmunosuppressed patients.1 The authors assessed the epidemiology of melanoma in close to 140 000 white patients based on who received a transplant in the United States. Invasive melanoma was diagnosed in 519 transplanted patients and in situ melanoma in 190 patients. The risk of invasive melanoma was elevated greater than 2-fold compared with the general population; most melanomas were detected on an “in situ” level with the most prominent location on head and neck. Tumors were classified as local only, regionally spread, or distantly spread. The risk for regional melanoma increased markedly within 4 years after the transplantation and remained consistently increased (1.5- to 2-fold) long term for the occurrence of in situ melanoma. A multivariate analysis for regional/distant stage melanoma, male, age, and an induction treatment with polyclonal antibodies represented particular risks. Survival was monitored in greater than 130 000 patients of which 27% died subsequent to melanoma compared to 12% in the general population. Melanoma-specific mortality was elevated 3-fold in transplant recipients, suggesting that tumor progression may be more aggressive in immunosuppressed patients. Moreover, the incidence of localized tumors was increased in patients on azathioprine potentially linked to an accelerated UVR-induced DNA damage in this patient group.2 However, the authors only documented immunosuppression at baseline. For regional- and distant-stage melanoma, the authors report a high risk shortly after transplantation that peaked at 4 years and was furthermore augmented when T-cell–depleting polyclonal antibodies were used. Of interest, melanoma incidence declined subsequent to graft failure in kidney recipients when immunosuppression had been discontinued or significantly reduced. The authors postulate that patients might have melanocytic precursors or early-stage melanomas undiagnosed at the time of transplantation that progressed rapidly with intense immunosuppression. Of note, melanomas express a range of neoantigens that can serve as a target for T cells. This article highlights the importance of screening patients on the waitlist thoroughly before transplantation to remove small melanomas and precursor lesions in time. REFERENCES Dahlke E, Murray CA, Kitchen J, et al. Systematic review of melanoma incidence and prognosis in solid organ transplant recipients. Transplant Res. 2014;3:10. Clarke LE, Warf BM, Flake DD, et al. Clinical validation of a gene expression signature that differentiates benign nevi from malignant melanoma. J Cutan Pathol. 2015;42:244–252. Preformed Circulating HLA-Specific Memory B Cells Predict High Risk of Humoral Rejection in Kidney Transplantation. Lucia M, Luque S, and Crespo E, et al. Kidney Int. 15 July 2015 Traditionally, clinicians use donor-specific antibodies (DSA) to assess the risk for antibody-mediated rejection in transplant candidates. It has been recognized that HLA-specific antibodies appear and disappear from time to time, and that it is possible to get histological evidence of humeral rejection in the absence of circulating DSAs. The authors investigated the significance of the memory B-cell pool in patients with antibody-mediated rejection in addition to highly sensitized patients on the waitlist; nonsensitized patients or transplanted patients who did not experience humoral rejections served as controls. The authors developed a B-cell ELIspot assay to detect circulating HLA-specific memory B Cells (mBC) capable of producing anti-class I/II HLA antibodies subsequent to polyclonal stimulation. Sensitized patients on the waitlist and patients who experienced an episode of antibody-mediated rejection demonstrated a detectable broad range of HLA-sp mBC even before transplantation. Moreover, the authors reported on a significant correlation of HLA sp mBC responses and acute vascular lesions by histology. Donor-specific mBC responses were detectable in 10/16 patients who developed antibody-mediated rejection, even before transplantation. Monitoring HLA-sp mBC seems to be more sensitive and specific than monitoring DSA in transplanted patients. HLA-specific mBC responses were able to predict HLA-specific antibody responses and humoral rejections early and accurately. Moreover, the presence of HLA-specific mBC predicted a rapid differentiation into antibody-producing cells when in contact with specific HLA antigens in presensitized patients.