ABSTRACT
RESUMEN El síndrome periódico asociado al receptor del factor de necrosis tumoral (TRAPS), se caracteriza por episodios de fiebre de más de 10 días de duración, mialgias migratorias, pseudocelulitis, dolor abdominal y edema bipalpebral. Su principal complicación es la amiloidosis y la falla renal producida por el estado inflamatorio crónico. Es una enfermedad autosómica dominante por mutación en el gen TNFRSF1A que codifica el receptor 1 del factor de necrosis tumoral (TNF). En las hipótesis elaboradas para explicar la enfermedad se describen la alteración en la liberación del receptor de TNF mutado, la activación del factor nuclear potenciador de las cadenas ligeras kappa de las células B activadas (NFkB) de forma independiente, las proteínas mal plegadas y alteraciones en el tráfico del receptor mutado, llevando a la acumulación de especies reactivas del oxígeno y defectos en la muerte celular por autofagia y apoptosis. Se han dirigido muchos esfuerzos en descubrir las bases inmunopatogénicas del TRAPS, dificultado por el elevado número de mutaciones encontradas, que se traducen en diferentes mecanismos y formas de presentación de la enfermedad. El tratamiento se basa en el bloqueo del TNF y de la interleuquina-1 (IL-1), la mejor comprensión de la inmunopatogénesis podría permitir un mejor seguimiento de los pacientes y el empleo de otras terapias.
SUMMARY Tumor necrosis factor receptor periodic syndrome (TRAPS) is characterized by episodes of fever of more than 10 days of duration, migratory myalgias, pseudocellulitis, abdominal pain and bipalpebral edema. It´s main complication is amyloidosis and renal failure caused by the chronic inflammatory state. It is an autosomal dominant disease, by mutation in the TNFRSF1A gene encoding tumor necrosis factor (TNF) receptor 1. Among the hypotheses to explain the disease have been proposed the alteration in the release of the mutated TNF receptor; the activation of nuclear factor enhancer of the kappa light chains of independently activated B cells (NFkB); poorly folded proteins, and alterations in the traffic of the mutated receptor. All of them, leading to the accumulation of reactive oxygen species and defects in cell death by autophagy and apoptosis. Many efforts have been directed to discover the immunopathogenic bases of TRAPS, which has been hampered by the high number of mutations found, which translate different mechanisms and forms of presentation of the disease. The treatment is based on the blockade of TNF and interleukin-1 (IL-1). The better understanding of immunopathogenesis could allow better monitoring of patients and the use of other therapies.
Subject(s)
Humans , Receptors, Tumor Necrosis Factor , Necrosis , NeoplasmsABSTRACT
Objective To investigate the correlation of cervical cancer and cervical intraepithelial neoplasia with expression level of serum soluble tumor necrosis factor receptor Ⅰ and Ⅱ.Methods A total of 915 recruited women in middle or advanced age were treated in our hospital from January 2015 to January 2017.Participants were assigned to one of five groups:group A (n=432) as control subjects;group B (n 89) diagnosed as cervical intraepithelial neoplasia Ⅰ;group C (n=94)as cervical intraepithelial neoplasia Ⅱ;group D (n=175) as cervical intraepithelial neoplasia Ⅲ;group E (n=125) as cervical cancer.The expression level of serum tumor necrosis factor receptor (sTNFR)was detected by enzyme linked immunosorbent assay.Results The level of sTNFR Ⅰ was much lower in the group A (0.869±0.243)μg/L than in the group B (1.127±0.435)μg/L,C (1.164±0.471)μg/L,D (1.206±0.693)μg/L,and E (1.836± 1.216)μg/L (t =7.782,8.741,8.860,and 15.523,all P＜0.001).The level of sTNFR Ⅰ in the group E was much higher than in the groups B,C,and D (t=5.263,5.077,and 5.684,all P＜0.001).No statistical significance was found in sTNFR Ⅰ level between B,C and D groups.The level of sTNFR Ⅱ was much lower in the group A (1.633±0.402)μg/L than in the group B (1.872±0.526)μg/L,C (1.895±0.402)μg/L,D (1.946±0.604)μg/L,and E (3.192±1.145)μg/L (t=4.824,5.254,7.446,and 23.731,all P＜0.001).The level of sTNFR Ⅱ was much higher in the group E than in the groups B,C,and D (t =10.136,10.501,and 12.216,all P＜0.001).There was no significant difference in sTNFR Ⅱ levels between the groups B,C,and D groups (all P ＞ 0.05).Conclusions Cervical cancer and cervical intraepithelial neoplasia are correlated with level of serum tumor necrosis factor receptors.