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Two cases of focal scrotal vitiligo successfully treated by autologous cultured melanocyte transplantation.

ABSTRACT: Vitiligo is an acquired cutaneous depigmentation disorder which has a deleterious effect on the psychosexual function of many individuals; the genitalia are the common site for depigmentation. Here, the authors report two cases of focal vitiligo affecting the scrotum of the genital organs which were successfully treated by autologous cultured melanocyte transplantation. Autologous cultured melanocyte transplantation on the scrotum is shown to be a relative effective method of treatment for vitiligo.

SUBMITTER: Li X

PROVIDER: S-EPMC4065275 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Two cases of focal scrotal vitiligo successfully treated by autologous cultured melanocyte transplantation.

Li Xiaowen X Hong Weisong W Xu Ai-E AE

Dermatology and therapy 20140327 1

Vitiligo is an acquired cutaneous depigmentation disorder which has a deleterious effect on the psychosexual function of many individuals; the genitalia are the common site for depigmentation. Here, the authors report two cases of focal vitiligo affecting the scrotum of the genital organs which were successfully treated by autologous cultured melanocyte transplantation. Autologous cultured melanocyte transplantation on the scrotum is shown to be a relative effective method of treatment for vitil ...[more]

PMID: 24671856

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Project description:BackgroundOxidative stress has a vital role in the early stages of vitiligo. Autoantigens released from apoptotic melanocytes (MC) under oxidative stress are involved in the presentation and recognition of antigens. However, the transport of autoantigens to the cell surface and their release to the extracellular environment are still unclear. Apoptotic bodies (ABs) have always been considered as a key source of immunomodulators and autoantigens. Yet, the role of ABs in the immune mechanism of vitiligo is still unknown.PurposeTo explore whether MC's autoantigens translocate into ABs during oxidative stress-induced apoptosis and study the molecular mechanisms underlying autoantigen migration and AB formation.MethodsPIG3V (an immortalized human vitiligo melanocyte cell line) were treated with H2O2, and ABs were separated. Transmission electron microscopy, flow cytometry, Western blot, mass spectrometry, and other methods were used to determine the relocation of specific antigens in PIG3V cells to ABs. After pretreatment with specific inhibitors (Rho kinase (Y-27632), myosin light chain kinase (MLCK, ML-9), pan-caspase (zVAD-FMK), and JNK (SP600125)), the pathway of autoantigen translocation into ABs and the formation of apoptotic bodies were determined.ResultsWhen treated with 0.8 mM H2O2, ABs were released from these cells. Autoantigens such as tyrosinase-related protein 1 (TYRP-1) and cleavage nuclear membrane antigen Lamin A/C (Asp230) were concentrated in ABs. The expression of autoantigens and the formation of ABs increased in a time- and dose-dependent manner after treatment with H2O2, while the application of specific inhibitors inhibited the formation of apoptotic bodies, i.e., the expression of antigens.ConclusionVitiligo autoantigens translocate into ABs in the process of apoptosis induced by oxidative stress. The cytoskeletal protein activation pathway and the JNK-related apoptosis pathway are involved in the transport of autoantigens and the formation of ABs. ABs may be the key bridge between MC cell apoptosis and cellular immunity.

Project description:BackgroundTreatment with proteasome inhibitors like carfilzomib in patients with multiple myeloma (MM) can induce thrombotic microangiopathy (TMA) characterized by neurological symptoms, acute kidney injury, hemolysis and thrombocytopenia. Successful treatment with the monoclonal antibody eculizumab was described for these patients, but reports of ideal management and definitive treatment protocols are lacking.Case presentationThe first case describes a 43-years-old IgG-kappa-MM patient that developed TMA during the first course of carfilzomib-lenalidomide-dexamethasone (KRd) consolidation after autologous stem cell transplantation (ASCT). In the second case, a 59-years-old IgG-kappa-MM patient showed late-onset TMA during the fourth and last cycle of elotuzumab-KRd consolidation within the DSMM XVII study of the German study group MM (DSMM; clinicalTrials.gov Identifier: NCT03948035). Concurrently, he suffered from influenza A/B infection. Both patients had a high TMA-index for a poor prognosis of TMA. Therapeutically, in both patients plasma exchange (TPE) was initiated as soon as TMA was diagnosed. In patient #1, dialysis became necessary. For both patients, only when the complement inhibitor eculizumab was administered, kidney function and blood values impressively improved.ConclusionIn this small case series, two patients with MM developed TMA due to carfilzomib treatment (CFZ-TMA), the second patient as a late-onset form. Even though TMA could have been elicited by influenza in the second patient and occurred after ASCT in both patients, with cases of TMA post-transplantation in MM being described, a relation of TMA and carfilzomib treatment was most likely. In both patients, treatment with eculizumab over two months efficiently treated TMA without recurrence and with both patients remaining responsive months after TMA onset. Taken together, we describe two cases of TMA in MM patients on carfilzomib-combination treatment, showing similar courses of this severe adverse reaction, with good responses to two months of eculizumab treatment.

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Two cases of focal scrotal vitiligo successfully treated by autologous cultured melanocyte transplantation.

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Two cases of focal scrotal vitiligo successfully treated by autologous cultured melanocyte transplantation.

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