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New Markers for Cardiovascular Disease in Psoriatic Patients: Preliminary Study on Monocyte Phenotype, ADAMTS7, and mTOR Activity

2023 , Khanty Loyola , Claudio Karsulovic , CABRERA MORAGA, RAUL ALEJANDRO , Claudio Perez , HOJMAN CANO, LIA PAULA

Psoriasis is a skin disease with occasional involvement of non-cutaneous territories. Beyond the usual, cardiovascular events are more frequent in these patients and correlate only partially with disease activity, suggesting the presence of other unknown factors. We selected ten psoriatic patients without treatment in the last year and matched them for age and gender with eleven healthy subjects. Ficoll-extracted mononuclear cells were analyzed with flow cytometry for monocyte surface phenotype markers, intracellular NFκB/inflammasome-dependent interleukins, and chemotaxis receptor CXCR3. Using ELISA, patient serum was evaluated for ADAMTS7 and CXCL10. Inflammatory M1 monocytes showed higher levels of IL-1β and IL-6 in psoriatic patients. M2 monocytes also showed higher levels of intracellular inflammatory cytokines. Nevertheless, IL-6 values were higher compared to other monocytes and IL-1β. The mTORC activation markers ADAMTS7 and S6Rp were higher in psoriatic patients than in healthy controls. In psoriatic patients, serum levels of ADAMTS7 were elevated, and M2 monocytes showed a distinct inflammatory response with higher relative levels of NFκB-dependent IL-6 and less activity of the CXCR3–CXCL10 chemotactic pathway. These data suggest pathways with potential markers for prediction and early detection of cardiovascular risk in psoriatic patients.

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Cardiovascular Disease-Associated Skin Conditions

2022 , HOJMAN CANO, LIA PAULA , Claudio Karsulovic

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Pivotal Role of mTOR in Non-Skin Manifestations of Psoriasis

2024 , Ka Joo , Claudio Karsulovic , Milisa Sore , HOJMAN CANO, LIA PAULA

Psoriasis is a chronic inflammatory condition affecting 2% of the Western population. It includes diverse manifestations influenced by genetic predisposition, environmental factors, and immune status. The sustained activation of mTOR is a key element in psoriasis pathogenesis, leading to an uncontrolled proliferation of cytokines. Furthermore, mTOR activation has been linked with the transition from psoriasis to non-skin manifestations such as psoriatic arthritis and cardiovascular events. While therapies targeting pro-inflammatory cytokines have shown efficacy, additional pathways may offer therapeutic potential. The PI3K/Akt/mTOR pathway, known for its role in cell growth, proliferation, and metabolism, has emerged as a potential therapeutic target in psoriasis. This review explores the relevance of mTOR in psoriasis pathophysiology, focusing on its involvement in cutaneous and atheromatous plaque proliferation, psoriatic arthritis, and cardiovascular disease. The activation of mTOR promotes keratinocyte and synovial cell proliferation, contributing to plaque formation and joint inflammation. Moreover, mTOR activation may exacerbate the cardiovascular risk by promoting pro-inflammatory cytokine production and dysregulation lipid and glucose metabolism. The inhibition of mTOR has shown promise in preclinical studies, reducing skin inflammation and plaque proliferation. Furthermore, mTOR inhibition may mitigate cardiovascular risk by modulating cholesterol metabolism and attenuating atherosclerosis progression. Understanding the role of mTOR in psoriasis, psoriatic arthritis, and cardiovascular disease provides insight into the potential treatment avenues and sheds light on the complex interplay of the immune and metabolic pathways in these conditions.

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Lupus eritematoso neonatal, caso clínico

2023 , Catalina Montané , HOJMAN CANO, LIA PAULA , Trinidad Hasbún Zegpi

El lupus eritematoso neonatal (LEN) es una patología autoinmune muy infrecuente, que ocurre en neonatos de madres que presentan auto-anticuerpos para antígenos citoplasmáticos del Síndrome de Sjögren. En la mayoría de los casos, la evolución es benigna hacia la resolución espontánea, pero existe un grupo de pacientes que desarrollan compromiso severo del tejido de conducción miocárdico, por lo que su detección oportuna es fundamental. Objetivo: Describir un caso clínico característico de lupus eritematoso neonatal y destacar la importancia del diagnóstico oportuno en madre y neonato. Caso Clínico: Mujer de 33 años, con antecedente de hipertensión arterial, consulta en dermatología por su neonato de 15 días de vida de sexo masculino, quien presenta aparición reciente de placas redondeadas, eritematosas, de bordes solevantados, no descamativas, compatibles con LEN. Se descartó compromiso de conducción miocárdica. En los exámenes del neonato destacaba neutropenia moderada, elevación leve de transaminasas y anticuerpos antiRo y antiLa positivos. En interrogación dirigida, la madre refiere historia personal de síntomas compatibles con enfermedades del tejido conectivo, tales como fatiga, alopecia y xeroftalmia. Se solicitan anticuerpos antinucleares a la madre, quien presenta título de 1/1280 con patrón moteado, anticuerpos anti Ro y La y anticuerpos anti-DNA doble hebra positivos, y Test de Schirmer compatible con ojo seco, por lo que se diagnostica Lupus Eritematoso Sistémico con Síndrome de Sjögren asociado. Se realiza seguimiento al lactante por 5 meses con remisión de los signos cutáneos y normalización de los exámenes de laboratorio. Conclusiones: Si bien, las manifestaciones cutáneas de LEN son transitorias y benignas en el neonato, estas pueden ir acompañadas de complicaciones de riesgo vital que requieren una búsqueda activa y un manejo oportuno por el equipo médico. Un 25% de las madres de hijos con LEN son asintomáticas, o desconocen su diagnóstico de LES previo al parto, por lo que el diagnóstico oportuno de LEN en un neonato permite diagnosticar a las madres asintomáticas, optimizando su seguimiento y manejo.

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Parvovirus B19: A DNA virus associated with multiple cutaneous manifestations

2018 , Gabriel Neely , CABRERA MORAGA, RAUL ALEJANDRO , HOJMAN CANO, LIA PAULA

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Non-Canonical WNT/Wnt5a Pathway Activity in Circulating Monocytes of Untreated Psoriatic Patients: An Exploratory Study of Its Association with Inflammatory Cytokines and Cardiovascular Risk Marker-ADAMTS7

2023 , Claudio Karsulovic , Khanty Loyola , CABRERA MORAGA, RAUL ALEJANDRO , Claudio Perez , Lia Hojman

The leading cause of death in psoriasis is cardiovascular disease. The determinants that induce the increase in this risk are not known. The systemic inflammatory process is dependent on lymphocytes and monocytes, as has been proposed. However, adaptation modules such as mTOR have recently been mentioned as having a role. Other factors, such as WNT and its non-canonical WNT5a-inducing pathway, are relevant in inflammation, cell migration, and neoangiogenesis. Thus, we studied circulating monocytes from untreated severe psoriatic patients and characterized inflammatory cytokines, chemokines, mTOR activity, and the cardiovascular risk marker ADAMTS7. Peripheral blood from ten severely psoriatic patients (Psoriasis severity index greater than 10) was extracted and age- and sex-matched with healthy subjects. Surface and intracellular flow cytometry were performed for cytokine, chemokine receptors, and mTOR activity. ADAMTS7 was measured using ELISA. Psoriatic patients had a higher frequency of WNT5a+ cells in monocytes, which also had higher levels of IL-1β, IL-6, CXCR3, CCR2, and phosphorylated S6R protein. We found that M1 monocytes are dominant in the WNT5a+ cell group, and intracellular levels of WNT5a were also augmented. Levels of WNT5a were correlated with ADAMTS7, a blood marker related to the pathogenesis of atheromatosis. WNT5a could be relevant to the cardiovascular risk of psoriatic patients considering its association with higher levels of inflammatory cytokines, chemokine receptors and the pro-atherogenic profile of circulating monocytes.

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Follicular vitiligo: dermatoscopic features of a new subtype of vitiligo

2019 , CABRERA MORAGA, RAUL ALEJANDRO , Francisca Reculé , Lía Hojman , Jorge Larrondo

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The Role of CXCL10 and IL-18 as Markers of Repigmentation Response in Nonsegmental Vitiligo Treated with Narrowband UVB Phototherapy: A Prospective Cohort Study

2021 , HOJMAN CANO, LIA PAULA , Claudio Karsulovic , CABRERA MORAGA, RAUL ALEJANDRO , Fabian Tempio , Claudio Perez , Mercedes López