RESUMO
Introducción. La infección por el HIV-1 induce un estado de inflamación crónico en el que participan los inflamasomas. El incremento de los parámetros inflamatorios es mayor en individuos con replicación viral activa que en aquellos con control de la replicación viral. Este proceso desencadena alteraciones metabólicas relacionadas con cambios en el perfil lipídico, lo cual podría incrementar el riesgo de eventos cardiovasculares, incluso en pacientes con terapia antirretroviral. Objetivo. Establecer si existe correlación entre la expresión de los componentes de los inflamasomas y los marcadores de riesgo cardiovascular en individuos con control de la replicación viral y en aquellos con replicación viral activa con terapia antirretroviral o sin ella. Materiales y métodos. Se estudiaron 13 individuos con control de la replicación viral y 40 con replicación viral activa (19 sin terapia antirretroviral y 31 con terapia). Se evaluaron los marcadores clásicos de riesgo cardiovascular y se cuantificó mediante RT-PCR la expresión de los componentes de los inflamasomas (NLRP1, NLRP3, NLRC4, AIM2, ASC, IL-1ß, IL-18 y caspasa-1), TLR2, TLR4, TGF-ß e IL-10. Resultados. Se observó que los pacientes con replicación viral activa y con terapia antirretroviral presentaron un incremento en la expresión de TLR2, TLR4 e IL-18, comparados con los controladores del HIV-1. Además, mostraron grandes valores de triglicéridos y lipoproteína de muy baja densidad (Very Low Density Lipopretein, VLDL), lo que se correlaciona positivamente con la expresión de los componentes de los inflamasomas NLRP1, NLRP3, NLRC4, AIM2, ASC y caspasa-1. Conclusión. El aumento en la expresión de los componentes de los inflamasomas en los individuos con replicación viral activa y con terapia antirretroviral se correlacionó con las concentraciones de triglicéridos y VLDL, lo que sugiere el papel de la activación inmunitaria y la terapia antirretroviral en el riesgo cardiovascular.
Introduction: HIV-1 infection induces a chronic inflammatory state in which inflammasomes participate. The increase in inflammatory parameters is higher in individuals with active viral replication (progressors) than in those with viral control (HIV-1 controllers). This process triggers metabolic alterations related to changes in the lipid profile, which could increase the risk of cardiovascular events, even in patients with antiretroviral therapy. Objective: To establish whether there was a correlation between the expression of inflammasome components and cardiovascular risk markers in HIV-1 controllers and progressors with or without antiretroviral therapy. Materials and methods: We studied 13 HIV-1 controllers and 40 progressors (19 without antiretroviral therapy and 31 with therapy) and evaluated in them classic markers of cardiovascular risk. Using RT-PCR we quantified the expression of inflammasome components (NLRP1, NLRP3, NLRC4, AIM2, ASC, IL-1ß, IL-18, and caspase-1), TLR2, TLR4, TGF-ß, and IL-10. Results: Progressors with antiretroviral therapy had an increased expression of TLR2, TLR4, and IL-18 compared to HIV-1 controllers. They also showed high levels of triglycerides and VLDL, which positively correlated with the expression of the inflammasome components NLRP1, NLRP3, NLRC4, AIM2, ASC, and caspase-1. Conclusion: Progressors receiving antiretroviral therapy exhibited an increased expression of the inflammasome components, which correlated with the levels of triglycerides and VLDL. This supports the role of inflammation in cardiovascular risk during HIV-1 infection.
Assuntos
HIV-1 , Inflamassomos , Replicação Viral , CardiopatiasRESUMO
BACKGROUND: Ichthyosis is a heterogeneous group of diseases caused by genetic disorders related to skin formation. They are characterized by generalized dry skin, scaling, hyperkeratosis and frequently associated with erythroderma. Among its different types, harlequin ichthyosis (HI) stands out due to its severity. HI is caused by mutations in the ABCA12 gene, which encodes essential proteins in epidermal lipid transport, and it helps maintain the homeostasis of the stratum corneum of the epidermis. However, due to the wide spectrum of genetic alterations that can cause ichthyosis, holistic medical care, and genetic studies are required to improve the diagnosis and outcomes of these diseases. CASE PRESENTATION: Here, we presented the case of a 19 years old male patient who was a premature infant and exhibited clinical features consistent with HI, including bright yellow hyperkeratotic plates with erythematous fissures that covered his entire body like a collodion baby. Currently, he exhibited erythroderma, photosensitivity, ectropion, auricular pavilion alterations, and musculoskeletal disorders, such as equinovarus feet, fingers, hands, and hypoplastic feet with contractures in flexion and marked difficulty in fine motor skills. In addition, he presented dyschromatopsia, Achilles reflex hyporeflexia, slight speech, dental alteration and deficient cognitive performance. After the genetic sequencing, variants were found in ABCA12 and HRNR which are related to several skin diseases, including ichthyosis. CONCLUSIONS: Although in clinical practice, ichthyosis is a common entity, a severe type of ichthyosis is presented, highlighting the importance of appropriate genetic diagnosis, given the broad spectrum of genetic alterations with similar phenotypic and clinical characteristics. These pathologies must be known to guarantee initial support measures to prevent complications and offer multidisciplinary management to those patients.
