Tumor necrosis factor-alpha inhibitor treatment for sarcoidosis

Sarcoidosis is a chronic multisystem disease of unknown etiology, characterized by noncaseating granulomatous infiltration of virtually any organ system. Treatment is often undertaken in an attempt to resolve symptoms or prevent progression to organ failure. Previous studies have suggested a prominent role for tumor necrosis factor-alpha (TNF-α) in the inflammatory process seen in sarcoidosis. TNF-α and interleukin-1 are released by alveolar macrophages in patients with active lung disease. Corticosteroids have proved to be efficacious in the treatment of sarcoidosis, possibly by suppressing the production of TNF-α and other cytokines. Three agents are currently available as specific TNF antagonists: etanercept, infliximab, and adalimumab. Although data from noncomparative trials suggest that all three have comparable therapeutic effects in rheumatoid arthritis, their effects in a granulomatous disease such as sarcoidosis are less consistent. In this review, current data on the effectiveness are summarized

A GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations

Archivo correspondiente a la versión FREE en la web de la revistaA single-nucleotide polymorphism (SNP) at the IL12RB2 locus showed a suggestive association signal in a previously published genome-wide association study (GWAS) in systemic sclerosis (SSc). Aiming to reveal the possible implication of the IL12RB2 gene in SSc, we conducted a follow-up study of this locus in different Caucasian cohorts. We analyzed 10 GWAS-genotyped SNPs in the IL12RB2 region (2309 SSc patients and 5161 controls). We then selected three SNPs (rs3790567, rs3790566 and rs924080) based on their significance level in the GWAS, for follow-up in an independent European cohort comprising 3344 SSc and 3848 controls. The most-associated SNP (rs3790567) was further tested in an independent cohort comprising 597 SSc patients and 1139 controls from the USA. After conditional logistic regression analysis of the GWAS data, we selected rs3790567 [P(MH)= 1.92 × 10(-5) odds ratio (OR) = 1.19] as the genetic variant with the firmest independent association observed in the analyzed GWAS peak of association. After the first follow-up phase, only the association of rs3790567 was consistent (P(MH)= 4.84 × 10(-3) OR = 1.12). The second follow-up phase confirmed this finding (P(χ2) = 2.82 × 10(-4) OR = 1.34). After performing overall pooled-analysis of all the cohorts included in the present study, the association found for the rs3790567 SNP in the IL12RB2 gene region reached GWAS-level significant association (P(MH)= 2.82 × 10(-9) OR = 1.17). Our data clearly support the IL12RB2 genetic association with SSc, and suggest a relevant role of the interleukin 12 signaling pathway in SSc pathogenesis.This work was supported by the following grants: J.M. was funded by GEN-FER from the Spanish Society of Rheumatol- ogy, SAF2009-11110 from the Spanish Ministry of Science, CTS-4977 from Junta de Andalucı́a, Spain, in part by Redes Temáticas de Investigación Cooperativa Sanitaria Program, RD08/0075 (RIER) from Instituto de Salud Carlos III (ISCIII), Spain and by Fondo Europeo de Desarrollo Regional (FEDER). T.R.D.J.R. was funded by the VIDI laureate from the Dutch Association of Research (NWO) and Dutch Arthritis Foundation (National Reumafonds). J.M. and T.R.D.J.R. were sponsored by the Orphan Disease Program grant from the Euro- pean League Against Rheumatism (EULAR). B.P.C.K. is sup- ported by the Dutch Diabetes Research Foundation (grant 2008.40.001) and the Dutch Arthritis Foundation (Reumafonds, grant NR 09-1-408). T.W. was granted by DFG WI 1031/6.1 and DFG KFO 250 TP03. N.O. was funded by PI-0590-2010, Con- sejerı́a de Salud, Junta de Andalucı́a, Spain. The USA studies were supported by NIH/NIAMS Scleroderma Registry and DNA Repository (N01-AR-0-2251), NIH/NIAMS-RO1- AR055258 and NIH/NIAMS Center of Research Translation in Scleroderma (1P50AR054144) and the Department of Defense Congressionally Directed Medical Research Programs (W81XWH-07-01-0111)

Personality disorders and emotional variables in patients with lupus

El lupus eritematoso sistémico (LES) es una enfermedad de carácter autoinmune que afecta principalmente a mujeres en edad fértil. Los síntomas más comunes de los pacientes incluyen dolor articular, erupciones cutáneas, cansancio o fatiga y dificultad en la respiración. Aunque el curso de la enfermedad es crónico, evoluciona normalmente en forma de brotes, que se alternan con periodos de remisión relativa. Si bien la etiología es desconocida, se sabe que existe una base genética predisponente y diversos factores ambientales que pueden actuar como desencadenantes. Entre éstos destacan la luz ultravioleta, las infecciones (especialmente virales), el embarazo y diversos fármacos. Además, diferentes variables psicológicas se han relacionado con la exacerbación de la enfermedad, de las cuales una de las más frecuentes es el estrés. Distintos estudios han mostrado que el estrés cotidiano produce un incremento en la sintomatología lúpica. Asimismo, los pacientes con lupus padecen también diversos trastornos psiquiátricos asociados a su enfermedad, cuya prevalencia oscila entre 20 y 66%, y se relaciona con una peor calidad de vida y una peor evolución y posesión de antecedentes psiquiátricos. En referencia concreta a las alteraciones de personalidad, investigaciones anteriores han hallado la existencia de una “tríada de personalidad” característica en pacientes con lupus, en que la depresión, la histeria y la hipocondriasis son sus componentes. Por lo anterior, el objetivo de este estudio ha sido comprobar la posible existencia de trastornos de la personalidad y su relación con otros trastornos afectivos en pacientes con lupus.Systemic lupus erythematosus (SLE), a prototype of the autoimmune diseases, is a multi-systemic disease characterized by an alteration in the immunological response, where the production of antibodies is directed against nuclear antigens, thus affecting many organs and systems. The course of this disease includes a wide range of clinical manifestations, different anatomo-pathological findings, and a series of immunological abnormalities. It is characterized by outbreaks and remissions. SLE can be manifested by general malaise, fever, fatigue, weight loss, skin rashes or joint inflammation, anemia, inflammation of the lymphatic glands, lowering of the defenses against infection, and cardiac, kidney, pulmonary and neurological alterations. In chronic dermatological lupus, only the skin is affected; this condition can present rash erythemas, etc. The recent introduction of new immunological diagnostic methods (antinuclear antibodies, anti-DNA antibodies, complementary fraction, etc.) has made it possible to recognize less severe forms of the disease, as well as its outbreaks and therapeutic guidelines. Different psychological variables have been associated with the exacerbation of the disease; one of the most notable is stress, and many patients with lupus also suffer diverse psychiatric and personality disorders associated with the disease, with a prevalence oscillating between 20% and 60%. Furthermore, these alterations have been associated with a lower quality of life, poorer evolution and psychiatric antecedents. In the specific case of personality alterations, previous research has found the existence of a “triad of personality” characteristics in patients with lupus. Depression, hysteria and hypochondria are the factors making up this triad. However, it has not been shown whether these personality disorders are just another symptom of the disease or a consequence of the emotional disorders produced by it. The purpose of this study was to test the possible existence of personality disorders and their relationship with other affective disorders in SLE

Differential protein expression in peripheral blood mononuclear cells (PBMCs) on patients withd systemic lupus erythematosus (SLE)

Comunicaciones a congreso

Effects of 12-week Aerobic Exercise on Arterial Stiffness, Inflammation, and Cardiorespiratory Fitness in Women with Systemic LUPUS Erythematosus: Non-Randomized Controlled Trial

This study assessed the effect of 12-week aerobic exercise on arterial stiffness (primary outcome), inflammation, oxidative stress, and cardiorespiratory fitness (secondary outcomes) in women with systemic lupus erythematosus (SLE). In a non-randomized clinical trial, 58 women with SLE were assigned to either aerobic exercise (n = 26) or usual care (n = 32). The intervention comprised 12 weeks of aerobic exercise (2 sessions X 75 min/week) between 40–75% of the individual’s heart rate reserve. At baseline and at week 12, arterial stiffness was assessed through pulse wave velocity (PWV), inflammatory (i.e., high-sensitivity C-reactive protein [hsCRP], tumor necrosis factor alpha [TFN- α], and inteleukin 6 [IL-6]) and oxidative stress (i.e., myeloperoxidase [MPO]) markers were obtained from blood samples, and cardiorespiratory fitness was assessed (Bruce test). There were no between-group differences in the changes in arterial stiffness (median PWV difference -0.034, 95% CI -0.42 to 0.36 m/s; p = 0.860) or hsCRP, TNF-α, IL-6, and MPO (all p > 0.05) at week 12. In comparison to the control group, the exercise group significantly increased cardiorespiratory fitness (median difference 2.26 minutes, 95% CI 0.98 to 3.55; p = 0.001). These results suggest that 12 weeks of progressive treadmill aerobic exercise increases cardiorespiratory fitness without exacerbating arterial stiffness, inflammation, or oxidative stress in women with SLE.This work was supported by Fundación para la Investigación Biosanitaria de Andalucía Oriental (grant number: PI-0525-2016) and the Ilustre Colegio Oficial de Médicos de Granada (Premios de Investigación 2017). BG-C was supported by the Spanish Ministry of Education (FPU15/00002)

COVID‑19 vaccine literacy in patients with systemic autoimmune diseases

Funding for open access charge: Universidad de Granada/CBUA.COVID-19 related infodemic is a threat to the successful COVID-19 vaccination campaigns. This might be especially apparent for patients with autoimmune diseases since there is no data available about the balance between benefits and risks of the newly developed COVID-19 vaccines in this population. We aim (i) to evaluate vaccine literacy skills in a population of patients with systemic autoimmune diseases, (ii) to examine the potential associations between vaccine literacy skills and sociodemographic characteristics and (iii) to analyze the relationships between attitudes, perceptions and beliefs about current vaccinations and vaccine literacy skills and sociodemographic characteristics. A cross-sectional study was conducted among 319 patients with systemic autoimmune diseases (92% females; 49.5% of patients in the 31–50 years age category). The vaccine literacy levels were determined using the Health Literacy about Vaccination in adulthood in Italian (HLVa-IT). Sociodemographic characteristics including gender, age, country and area of residence, civil status, socioeconomic status, educational attainment and occupational status were evaluated. The mean vaccine literacy functional and interactive-critical scores were 2.59 ± 0.74 and 3.07 ± 0.60, respectively. The vaccine literacy interactive-critical score was higher in females than in males (p = 0.048). Interactive-critical scores were associated with the area of residence, civil status and socioeconomic status, with the highest score in urban area of ≥ 100.000 inhabitants (p = 0.045), in widow patients (p = 0.023) and in patients with high socioeconomic status (p = 0.018). Significant differences were observed between the different education levels, for both the functional and the interactive-critical scores (p = 0.002 and p < 0.001, respectively), the highest score was observed in patients who completed a university degree. The level of vaccine literacy for functional and interactive-critical scales were medium. Area of residence, civil status and socioeconomic status represented determinants of vaccine literacy interactive-critical scale. Educational attainment also contributes to vaccine literacy functional scale. Insight into these factors is required to ensure an optimal vaccine literacy level in patients with autoimmune diseases.Universidad de Granada/CBU

Mesenteric Inflammatory Venoocclusive Disease in a Patient with Sjögren’s Syndrome

Mesenteric inflammatory venoocclusive disease is an uncommon cause of intestinal ischemia. Certain diseases, such as hypercoagulation disorders, autoimmune diseases, or drugs have been associated with the pathogenesis of mesenteric inflammatory venoocclusive disease. Here, we report a patient with Sjögren’s syndrome who underwent surgery for suspected acute appendicitis with a subsequent pathological diagnosis of mesenteric inflammatory venoocclusive disease

Azathioprine dose tailoring based on pharmacogenetic information: Insights of clinical implementation

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.biopha.2023.115706Azathioprine is commonly used as an immunosuppressive antimetabolite in the treatment of acute lymphoblastic leukemia, autoimmune disorders (such as Crohn's disease and rheumatoid arthritis), and in patients receiving organ transplants. Thiopurine-S-methyltransferase (TPMT) is a cytoplasmic trans-methylase catalyzing the S-methylation of thiopurines. The active metabolites obtained from thiopurines are hydrolyzed into inactive forms by the Nudix hydrolase 15 (NUDT15). The TPMT*2 (defined by rs1800462), *3A (defined by rs1800460 and rs1142345), *3B (defined by rs1800460), *3C (defined by rs1142345), *6 (defined by rs75543815), and NUDT15 rs116855232 genetic variant have been associated, with the highest level of evidence, with the response to azathioprine, and, the approved drug label for azathioprine and main pharmacogenetic dosing guidelines recommend starting with reduced initial doses in TPMT intermediate metabolizer (IM) patients and considering an alternative treatment in TPMT poor metabolizer (PM) patients. This study aims to assess the clinical impact of azathioprine dose tailoring based on TPMT genotyping studying the azathioprine toxicity and efficacy, treatment starts, and dose adjustments during follow-up, comparing TPMT IM/PM and normal metabolizer (NM) patients. It also studied the association of NUDT15 rs116855232 with response to azathioprine in patients receiving a tailored treatment based on TPMT and characterized the TMPT and NUDT15 studied variants in our population. Results show that azathioprine dose reduction in TPMT IM patients (TPMT*1/*2, *1/*3A, or *1/*3C genotypes) is related to lower toxicity events compared to TPMT NM (TPMT *1/*1 genotype), and lower azathioprine dose adjustments during follow-up without showing differences in the efficacy. The results support the hypothesis of existing other genetic variants affecting azathioprine toxicity

Oral Calcidiol Is More Effective Than Cholecalciferol Supplementation to Reach Adequate 25(OH)D Levels in Patients with Autoimmune Diseases Chronically Treated with Low Doses of Glucocorticoids: A "Real-Life" Study

Glucocorticoids (GCs) are the cornerstone of the therapy in many autoimmune and inflammatory diseases. However, it is well known that their use is a double edged sword, as their beneficial effects are associated almost universally with unwanted effects, as, for example glucocorticoid-induced osteoporosis (GIO). Over the last years, several clinical practice guidelines emphasize the need of preventing bone mass loss and reduce the incidence of fractures associated with GC use. Calcium and vitamin D supplementation, as adjunctive therapy, are included in all the practice guidelines. However, no standard vitamin D dose has been established. Several studies with postmenopausal women show that maintaining the levels above 30-33 ng/mL help improve the response to bisphosphonates. It is unknown if the response is the same in GIO, but in the clinical practice the levels are maintained at around the same values. In this study we demonstrate that patients with autoimmune diseases, undergoing glucocorticoid therapy, often present suboptimal 25(OH)D levels. Patients with higher body mass index and those receiving higher doses of glucocorticoids are at increased risk of having lower levels of 25(OH)D. In these patients, calcidiol supplementations are more effective than cholecalciferol to reach adequate 25(OH)D levels