Inflammatory Cutaneous Diseases in Renal Transplant Recipients

Savoia, Paola; Cavaliere, Giovanni; Zavattaro, Elisa; Veronese, Federica; Fava, Paolo

doi:10.3390/ijms17081362

Cited by 8 publications

(8 citation statements)

References 35 publications

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“…This result is counterintuitive because a reduced inflammatory response is expected in the presence of immunosuppression. Indeed, skin inflammatory conditions occur in about 15% of KT patients versus > 60% in the general population [27]. In addition to inflammatory infiltrates, the tumor microarchitecture was also examined using image analysis.…”

Section: Discussionmentioning

confidence: 99%

Kidney Transplant Modifies the Architecture and Microenvironment of Basal Cell Carcinomas

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Viggiano

Lee

et al. 2020

Kidney Blood Press Res

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Background/Aims: Basal cell carcinoma (BCC) is a frequent type of nonmelanoma skin cancer, which shows a greater prevalence in kidney-transplanted (KT) patients than in the general population. The study of this tumor in KT patients may allow us to understand the influence of the tumor inflammatory microenvironment on cancer behavior, and to design new image analysis methods to determine prognosis and apply personalized medicine. The major hypothesis of the present work is that antirejection drugs, by modifying the B-cell/T-cell balance, induce measurable differences in tumoral cell microarchitecture and in the inflammatory microenvironment in KT patients compared to nontransplanted controls. Methods: In this retrospective study in an Italian cohort including 15 KT patients and 15 control subjects from the general population who developed BCC, we analyzed tissue microarchitecture and inflammatory infiltrates of BCC using state-of-the-art nonlinear image analysis techniques such as fractal dimension and sample entropy of internuclear distances. Results: KT patients showed a nonsignificant trend to a greater number of nuclei in the basal cell layer compared to non-KT controls and subtle changes in the intact skin compared to controls. Similarly, the number of mitoses per unit length was almost doubled in the patients with KT compared to controls. However, when the number of mitotic cells was normalized by the total number of cells in the basal layer (mitotic index), these differences were not significant, although a clear trend was still present. Finally, KT patients showed a nonsignificant trend to an increased density of inflammatory cells close to the tumoral cell layer. When considering the intact skin, this difference was significant, with a 70% increase in the density of inflammatory cells. Conclusion: Data comparing the microarchitecture of BCC in normal subjects and KT patients are scanty, and the present study is the first to use nonlinear image analysis techniques to this aim. The observed differences underscore the relevance of T-cell suppression in cancer behavior. These data suggest that BCC develops in treated patients with specific biological characteristics which should be further analyzed in terms of therapeutic response.pipeline image analysis strategy to evaluate and assess the histology of basal cell layers in KT patients with BCC. Previous observations showed that BCC was clinically similar in the KT and the general population [12]: BCC occurrence was increased at the level of the head and neck region at an advanced age and the level of the trunk at a younger age. Furthermore, the literature on gender prevalence is somewhat inconsistent regarding BCC in KT, but in the general population males are more often affected than females (as in our sample). Finally, BCC is reported to have poor or scanty inflammatory response in the general popu-

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Section: Discussionmentioning

confidence: 99%

Kidney Transplant Modifies the Architecture and Microenvironment of Basal Cell Carcinomas

Capasso

Viggiano

Lee

et al. 2020

Kidney Blood Press Res

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“…The strength of our causespecific model was that BCEo and IS drugs were considered at each measurement in a time-dependent manner and thus contributed to overcome the uncertainties about the impact of CNI and oral corticoids association on BCEo during follow-up. Of important note, none of the KTRs with HPR with a BCEo > 0.3 G/L had skin and/or cutaneous and/or gastro-intestinal symptoms in their medical history that could suggest an add-on eosinophilic disorder [51].…”

Section: Discussionmentioning

confidence: 98%

Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection

et al. 2021

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Background: Growing evidence suggest that type 2 immune effectors play a role in solid organ transplantation. The aim of this study was to evaluate the impact of blood count eosinophils (BCEo) on immunological outcomes in kidney transplant recipients with stable graft function after 3 months post-transplant. Method: We performed cause-specific Cox model considering BCEo, the use of calcineurin inhibitors and systemic corticoids as time-dependent explicative variables on a prospective cohort of 1013 kidney transplant patients who experienced kidney allograft rejection and/or the appearance of de novo donor specific antibodies after excluding common causes of increased BCEo.. Findings: BCEo 0.3 G/L was associated with a 3-fold increased risk of rejection independent of immunosuppressive regimen after 3 months post-transplant in patients without pre-transplant DSAs and with CNI-based immunosuppression. No association between BCEo either with donor specific antibodies or graft survival was noticed. Interpretation: These observations in this large cohort support the hypothesis of eosinophils in allo-immunity in human and claim for further mechanistic research.

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“…BCC:SCC ratio of 1:4), which is the opposite of the general population (23). The immunosuppressive regimen would be expected to reduce the inflammatory infiltrate, as evidenced by the reduced prevalence of inflammatory skin lesions in KT (24). Steroids are expected to decrease skin thickness.…”

Section: Discussionmentioning

confidence: 99%

Skin Architecture, Kidney Transplantation, and Their Relationship to Basal and Squamous Cell Carcinomas

et al. 2020

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Background/Aim: Squamous cell carcinoma (SCC) is highly prevalent in kidney transplant patients (KT).It is characterized by the presence of an inflammatory infiltrate. In this study, we examined the presence of similar infiltrates in intact skin, which could be regarded as a precancerous step. Patients and Methods: We retrospectively analyzed skin biopsies of 19 non-transplanted patients with a diagnosis of SCC or basal cell carcinoma (BCC) and 17 KT with either SCC or BCC. Results: KT showed increased inflammatory infiltrate in the subepithelial region, compared to non-transplanted patients. The density of basal cell nuclei was also different among the four groups with an interaction effect between tumor type and transplantation. The extent of inflammatory infiltrates did not correlate with the eGFR and proteinuria. Conclusion: KT with a non-melanoma skin cancer show increased intact skin inflammatory infiltrate and alterations in the density of the basal cell layer compared to non-transplanted patients.

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Inflammatory Cutaneous Diseases in Renal Transplant Recipients

Cited by 8 publications

References 35 publications

Kidney Transplant Modifies the Architecture and Microenvironment of Basal Cell Carcinomas

Kidney Transplant Modifies the Architecture and Microenvironment of Basal Cell Carcinomas

Time-dependent blood eosinophilia count increases the risk of kidney allograft rejection

Skin Architecture, Kidney Transplantation, and Their Relationship to Basal and Squamous Cell Carcinomas

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