A two sample mendelian randomization analysis investigates causal effects between gut microbiome and immune related Vasculitis.

Observational data suggest a link between gut microbiota and immune-related vasculitis, but causality remains unclear. A bidirectional mendelian randomization study was conducted using public genome-wide data. The inverse-variance-weighted (IVW) method identified associations and addressed heterogeneity.Families Clostridiaceae 1 and Actinomycetaceae correlated positively with granulomatosis with polyangiitis risk, while classes Lentisphaeria and Melainabacteria, and families Lachnospiraceae and Streptococcaceae showed negative associations. Behçet's disease was positively associated with the risk of family Streptococcaceae abundance. And other several gut microbiota constituents were identified as potential risk factors for immune-related vasculitis. Furthermore, combining positive association results from the IVW analysis revealed numerous shared gut microbiota constituents associated with immune-related vasculitis. MR analysis demonstrated a causal association between the gut microbiota and immune-related vasculitis, offering valuable insights for subsequent mechanistic and clinical investigations into microbiota-mediated immune-related vasculitis.

Association of Glutathione Transferase M1, T1, P1 and A1 Gene Polymorphism and Susceptibility to IgA Vasculitis.

Endothelial cell injury is a hallmark of IgA vasculitis (IgAV), possibly associated with various factors, including oxidative stress. Certain single nucleotide polymorphisms (SNPs) of glutathione S-transferases (GST) genes have been shown to increase susceptibility to oxidative stress. The objective of our study was to evaluate the gene polymorphisms of GSTM1, GSTT1, GSTP1, and GSTA1 in patients with IgAV. DNA was extracted from the blood of 124 children with IgAV and 168 age-matched healthy controls. A higher frequency of the GSTM1 null genotype was observed in patients with gastrointestinal (GI) system involvement compared to those without GI system involvement (51.5% vs. 28.6%, p = 0.011). Additionally, the GSTM1 null genotype was less prevalent (30.8% vs. 69.2%, p = 0.032), while the GSTP1 Val/Val genotype was significantly more prevalent in patients who developed urogenital complications (scrotal swelling) during the course of the disease (60% vs. 40%, p = 0.039). This study is the first to suggest an association between GSTM1 and GSTP1 polymorphisms and various phenotypes observed during the clinical course of IgAV in the pediatric population. However, it was performed on a national and likely single ethnic cohort, too small for definitive conclusions, so larger studies are needed to confirm this association.

Role of non-coding RNAs and exosomal non-coding RNAs in vasculitis: A narrative review.

A category of very uncommon systemic inflammatory blood vessel illnesses known as vasculitides. The pathogenesis and etiology of vasculitis are still poorly known. Despite all of the progress made in understanding the genetics and causes behind vasculitis, there is still more to learn. Epigenetic dysregulation is a significant contributor to immune-mediated illnesses, and epigenetic aberrancies in vasculitis are becoming more widely acknowledged. Less than 2 % of the genome contains protein-encoding DNA. Studies have shown that a variety of RNAs originating from the non-coding genome exist. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs) have attracted the most attention in recent years as they are becoming more and more important regulators of different biological processes, such as diseases of the veins. Extracellular vehicles (EVs) such as exosomes, are membrane-bound vesicular structures that break free either during programmed cell death, such as apoptosis, pyroptosis, and necroptosis or during cell activation. Exosomes may be involved in harmful ways in inflammation, procoagulation, autoimmune reactions, endothelial dysfunction/damage, intimal hyperplasia and angiogenesis, all of which may be significant in vasculitis. Herein, we summarized various non-coding RNAs that are involved in vasculitides pathogenesis. Moreover, we highlighted the role of exosomes in vasculitides.

Cambio de paradigma en las enfermedades autoinflamatorias monogénicas y las vasculitis sistémicas: el síndrome VEXAS / Paradigm shift in monogenic autoinflammatory diseases and systemic vasculitis: The VEXAS syndrome

A finales de 2020 se describió el síndrome VEXAS, como una enfermedad autoinflamatoria causada por variantes poscigóticas en el gen UBA1. Se presenta en varones adultos con fiebre recurrente, artralgias/artritis, condritis auricular/nasal, dermatosis neutrofílica, inflamación pulmonar, trombosis venosas y diferentes tipos de vasculitis. Los análisis muestran una respuesta de fase aguda elevada y anemia macrocítica. Es frecuente la coexistencia de mielodisplasia, y son características las vacuolas citoplasmáticas en precursores mieloides y eritroides en médula ósea. Los glucocorticoides a dosis medias-altas son eficaces, pero el resto de fármacos inmunodepresores, convencionales o biológicos, muestran una eficacia limitada o ausente. Azacitidina se ha asociado con una buena respuesta, sobre todo en pacientes con síndrome mielodisplásico acompañante. El trasplante alogénico de progenitores hematopoyéticos parece ser la única terapia curativa hasta el momento. El síndrome VEXAS ha supuesto un cambio de paradigma en el diagnóstico y tratamiento de las enfermedades autoinflamatorias y las vasculitis sistémicas. (AU)

VEXAS syndrome was described by the end of 2020 as an autoinflammatory disease caused by post-zygotic variants in the UBA1 gene. VEXAS syndrome occurs in adult males with recurrent fever, arthralgia/arthritis, ear/nose chondritis, neutrophilic dermatosis, lung inflammation, venous thrombosis, and different types of vasculitis. Common laboratory changes include raised acute phase reactants and macrocytic anemia. The coexistence of myelodysplasia is frequent, and bone marrow vacuolization of myeloid and erythroid precursors is characteristic. Glucocorticoids are effective at medium-high doses, but the remaining immunosuppressive drugs, either conventional or biological, have showed limited or absent efficacy. Azacitidine has been associated with a good response, especially in patients with accompanying myelodysplastic syndrome. Allogeneic hematopoietic stem cell transplantation appears to be the only curative therapy by now. VEXAS syndrome has become a paradigm shift in the diagnosis and treatment of autoinflammatory diseases and systemic vasculitis. (AU)

¿Son realmente útiles los anti-TNFα en vasculitis sistémicas? Experiencia en panarteritis nodosa / Are anti-TNF-α agents really useful in systemic vasculitis? Experience in polyarteritis nodosa

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Genética y ambiente: ¿factores etiopatogénicos de las vasculitis? / No disponible

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Marcadores de inflamación endotelial subclínica en una familia con hiperaldosteronismo familiar tipo I por mutación de novo / Subclinical endothelial inflammation markers in a family with type I familial hyperaldosteronism caused by a de novo mutation

Background: Type I familial hyperaldosteronism is caused by the presence of a chimaetic gene CYPl 1B1/CYP11BZ which encodes an enzyme with aldosterone synthetase activityregulated by adrenocorticotrophic hormone (ACTH). Therefore, in patients with FH I is possible to normalize the aldosterone levels with glucocorticoid treatment. Recently it has been shown that aldosterone plays a role in the production of endothelial oxidative stress and subclinical inflammation. Aim: To evaluate subclinical endothelial inflammation markers, Me Metalloproteinase 9 (MMP-9) and ultrasensitive C reactive protein (usPCR), before and after glucocorticoid treatment in family members with FH-I caused by a de novo mutation. Patients and methods: We report three subjects with FH-I in a single family (proband, father and sister). We confirmed the presence of a chimaeric CYPl 1B1/CYP11B2 gene by ¡ong-PCR in all of them. Paternal grandparents were unaffected by the mutation. The proband was a 13year-old boy with hypertension stage 2 (in agree to The JointNational Committee VII, JNC-vIl), with an aldosterone/plasma rennin activity ratio equal to 161. A DNA paternity test confirmed the parental relationship between the grandparents and father with the index case. MMP-9 and usPCR levels were determined by gelatin zymography and nephelometry, respectively. Results: All affected subjects had approximately a 50 percent increase in MMP-9 levels. Only the father had an elevated usPCR. The endothelial inflammation markers returned to normal range after glucocorticoid treatment. Conclusions: We report a family canying a FH-I caused by a de novo mutation. The elevation of endothelial inflammation markers in these patients and its normalization after glucocorticoid treatment provides new insight about the possible deleterious effect of aldosterone on the endothelium.

Edema hemorrágico agudo del lactante; una entidad poco conocida / No disponible

El edema hemorrágico agudo del lactante (EHAL) es una rara vasculitis leucocitoclástica que afecta a lactantes y niños hasta los 3 años de edad. Cursa con un cuadro clínico caracterizado por la rápida aparición de una extensa púrpura palpable, pero su pronóstico generalmente es muy bueno. Presentamos el caso de un lactante con EHAL y comentamos las similitudes y las diferencias que guarda este cuadro con la púrpura de Schonlein-Henoch (AU)

The acute hemorrhagic edema of infancy (AHEI) is an unusual variant of leukocitoclastic vasculitis affecting infants and children up to three years of age. Clinically it is characterised by a large palpable purpura with a dramatic appearance but an usually benign course. We present an infant with AHEI and compare this disorder with the Schonlein-Henoch purpura (AU)