HLA-B27 may modulate the interaction between ERAP1 polymorphisms and smoking in ankylosing spondylitis patients.

BACKGROUND: Ankylosing spondylitis (AS) is an autoimmune disease that affects the enthesis and synovial membrane of the spine, the sacroiliac vertebrae and peripheral joints. Genetic susceptibility to AS is mainly due to the presence of the HLA-B*27 (B27) allele, and endoplasmic reticulum aminopeptidase-1 (ERAP-1) plays a key role in antigen processing and presentation to HLA class I molecules. Tobacco consumption is one of the main environmental factors involved in the pathogenesis of various diseases, including AS. The objective of the present study was to evaluate the association and the interactive effects of variants of the ERAP1 gene with smoking in modulating the risk of AS. METHODS AND RESULTS: A case-control study in the Mexican population. The association of two functional variants of the ERAP1 gene (rs30187 and rs27044) in patients with AS was analyzed by the allelic discrimination method using TaqMan probes. B27 was typified by PCR-SSP. The interaction between the variants of ERAP1 and B27 and smoking was assessed using the multifactorial dimensionality reduction (MDR) method. There was no significant association of the two variants of ERAP1 in the cases compared with the controls (P > 0.05); however, a strong interaction between the variants and smoking could be demonstrated, with entropy values of 4.97% for rs30187 and 5.13% for rs27044. In addition, these interaction effects were increased in patients carrying the B27 allele. CONCLUSIONS: The rs30187 and rs27044 variants of the ERAP1 gene appear to potentiate the effect of smoking in patients with AS carrying the B27 allele.

[Importance of autoimmunity induced by SARS-CoV-2 and development of post-vaccination autoimmune diseases]. / Importancia de la autoinmunidad inducida por SARS-CoV-2 y desarrollo de enfermedades autoinmunes post-vacunación.

SARS-CoV-2, a virus belonging to the large family of coronavirus, aroused great interest following the outbreak of this new strain reported in 2019, in Wuhan China. Its clinical spectrum is highly variable, ranging from a self-limited disease to an acute respiratory distress syndrome with systemic clinical manifestations (COVID-19), in which the immune system plays a key role in the pathophysiology of this disease and in its severity; several studies show the prevalence of some autoimmune markers suggesting that they may lead to autoimmune states. The most important strategy worldwide to protect the population was the development of vaccines to induce immunity to severe COVID-19; however, vaccines have also been shown to have the ability to produce autoimmune states in a small percentage of the world's population; nevertheless, the best strategy remains vaccination. The aim of this review is to show the current overview of the mechanisms of SARS-CoV-2-induced autoimmunity and post-vaccination for a better understanding and identification of these in the population. Publications from 2019 to 2022 were reviewed in PubMed as the primary search source.

El SARS-CoV-2, un virus perteneciente a la gran familia de los coronavirus despertó gran interés después del brote de la nueva cepa reportada en 2019, en Wuhan, China. Las manifestaciones clínicas son variables: desde enfermedad con curación espontánea hasta síndrome de dificultad respiratoria aguda, con alteraciones clínicas sistémicas (COVID-19), donde el sistema inmunitario tiene participación importante en la fi-siopatología de la enfermedad y su gravedad. Diversos estudios demuestran la prevalencia de algunos marcadores autoinmunes, lo que sugiere que pueden conducir a estados de autoinmunidad. La estrategia más importante a nivel mundial para proteger a la población fue el desarrollo de vacunas para inducir inmunidad frente al COVID-19 grave; sin embargo, se ha demostrado que tienen la capacidad de producir estados autoinmunitarios en un pequeño porcentaje de la población; no obstante, siguen siendo la mejor estrategia de tratamiento. El objetivo de esta revisión es mostrar el panorama actual de los mecanismos de autoinmunidad inducidos por SARS-CoV-2 y la post-vacunación, para una mejor comprensión e identificación en la población. Se revisaron las publicaciones de 2019 a 2022 en PubMed como fuente principal de búsqueda.

Effect of smoking on the redox status of knee osteoarthritis: A preliminary study.

Even though smoking has been scarcely studied in osteoarthritis (OA) etiology, it is considered a controversial risk factor for the disease. Exposure to tobacco smoke has been reported to promote oxidative stress (OS) as part of the damage mechanism. The aim of this study was to assess whether smoking increases cartilage damage through the generation of OS. Peripheral blood (PB) and synovial fluid (SF) samples from patients with OA were analyzed. The samples were stratified according to smoking habit, Kellgren-Lawrence score, pain, and cotinine concentrations in PB. Malondialdehyde (MDA), methylglyoxal (MGO), advanced protein oxidation products (APOPs), and myeloperoxidase (MPO) were assessed; the activity of antioxidant enzymes such as gamma-glutamyl transferase (GGT), glutathione S-transferase (GST) and catalase (CAT), as well as the activity of arginase, which favors the destruction of cartilage, was determined. When stratified by age, for individuals <60 years, the levels of MDA and APOPs and the activity of MPO and GST were higher, as well as antioxidant system activity in the smoking group (OA-S). A greater degree of pain in the OA-S group increased the concentrations of APOPs and arginase activity (P < 0.01 and P < 0.05, respectively). Arginase activity increased significantly with a higher degree of pain (P < 0.01). Active smoking can be an important risk factor for the development of OA by inducing systemic OS in young adults, in addition to reducing antioxidant enzymes in older adults and enhancing the degree of pain and loss of cartilage.

Anti-inflammatory and Antioxidant Effect of Poly-gallic Acid (PGAL) in an In Vitro Model of Synovitis Induced by Monosodium Urate Crystals.

Gout is a chronic and degenerative disease that affects the joints and soft tissues because of the crystalline deposit of monosodium urate. The interaction between monosodium urate crystals (MSU) and synoviocytes generates oxidative and inflammatory states. These physiological characteristics have promoted the study of poly-gallic acid (PGAL), a poly-oxidized form of gallic acid reported to be effective in in vitro models of inflammation. The effect of PGAL in an in vitro model of oxidation and synovial inflammation induced by MSU was evaluated after 24 h of stimulation through the morphological changes, the determination of oxidative stress (OS), IL-1ß, and the phagocytosis of the MSU. A 20% reduction in synovial viability and the generation of vesicles were observed when they were exposed to MSU. When PGAL was used at 100 and 200 µg/ml, cell death was reduced by 30% and 17%, respectively. PGAL both doses reduce the vesicles generated by MSU. OS generation in synoviocytes exposed to 100 µg/ml and 200 µg/ml PGAL decreased by 1.28 and 1.46 arbitrary fluorescence units (AFU), respectively, compared to the OS in synoviocytes exposed to MSU (1.9 AFU). PGAL at 200 µg/ml inhibited IL-1ß by 100%, while PGAL at 100 µg/ml inhibited IL-1ß by 66%. The intracellular MSU decreased in synoviocytes stimulated with 100 µg/ml PGAL. The PGAL has a cytoprotective effect against damage caused by MSU in synoviocytes and can counteract the oxidative and inflammatory response induced by the crystals probably because it exerts actions at the membrane level that prevent phagocytosis of the crystals.