Contribución de los linfocitos T y los monocitos en el balance de citocinas de tipo 1 y 2 en la sangre periférica de pacientes con lupus eritematoso sistémico

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid. Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 5 de Julio de 200

Sarcoidosis and lymphoma mortality risk: An observational study from the Spanish National Registry

Introduction: Patients with sarcoidosis have a lower survival rate than the general population, in part due to cardiovascular disease, infections and neoplasms. Our objective was to evaluate the impact of haematological neoplasms (HN) and lymphomas on sarcoidosis patient mortality in a nation-wide analysis conducted in Spain, a country with a population of 47 million. Methods: Retrospective and observational comparison of the HN related deaths in sarcoidosis patients and the general Spanish population reported in the Spanish Hospital Discharge Database. To determine the impact of sarcoidosis on the risk of dying from each HN lineage, a binary logistic regression considering age, female sex, tobacco and alcohol consumption, was performed. Results: In the period 2016 and 2019, 139,531 in-hospital deaths from neoplasms were certified in Spain (77 in patients with sarcoidosis). Patients with sarcoidosis died at younger age than the general Spanish population (72.9 vs 77.6, p<0.001). Sarcoidosis patients presented a higher mortality risk from HN (20.8% vs 8.9%, p=0.001, OR=2.64, 95% CI 1.52-4.59), attributable to the higher proportion of deaths from non-Hodgkin lymphoma (NHL), (9.2% vs 2.9%, p=0.006, OR= 3.33, 95% CI 1.53-7.25) from both B cell (6.6% vs 2.5%, p=0.044, OR= 2.62, 95% 1.06-6.5) and T/NK cell lineages (2.6% vs 0.3%, p=0.024, OR= 7.88, 95% CI 1.92-32.29) as well as HN with uncertain behavior and myeloproliferative disorders (2.6% vs 0.3%, p=0.018, OR= 11.88, 95% CI 2.88-49.02). The mean age of sarcoidosis patients who died from HN (63.6 vs 71.9, p=0.032) and non-Hodgkin lymphoma (56.9 vs 71, p=0.009) was lower than that of the general population Conclusion: Patients with sarcoidosis present a higher risk of premature death from HN, including NHL from B, T/NK cell lineage and myeloproliferative disorders in comparison with the general Spanish population. In addition to developing strategies that might help to attenuate their occurrence and impact, such as decreasing the immunosuppressive burden, specific early-detection programs for these conditions should be investigated and considered carefully

Expression of human leukocyte antigen-G in systemic lupus erythematosus

The purpose of this study was to examine the expression of human leukocyte antigen-G (HLA-G) in patients with systemic lupus erythematosus (SLE) and its relation with interleukin-10 (IL-10) production. The study included 50 female SLE patients and 59 healthy female donors. HLA-G expression in peripheral blood and cutaneous biopsies was determined by flow cytometry and immunohistochemistry, respectively. Soluble HLA-G (sHLA-G) and IL-10 were quantified in serum samples by enzyme-linked immunosorbent assay. SLE patients presented with serum sHLA-G and IL-10 levels significantly higher than that observed in controls (median [interquartile range (IQR)] = 43.6 U/ml [23.2–150.2] vs 26.84 U/ml [6.0–45.2], p = 0.004; and 1.4 pg/ml [0–2.3] vs 0 pg/ml [0–1.5], p = 0.01, respectively). But no correlation was observed between sHLA-G and both IL-10 levels and the disease activity index for SLE patients. The expression of membrane HLA-G in peripheral lymphocytes from SLE patients was low, but higher than in controls (median [IQR] = 1.5% [0.6–1.8] and 0.3% [0.2–0.8], respectively; p = 0.02). Finally, these findings were in accordance with the weak expression of HLA-G in skin biopsies. Despite the fact that patients present higher levels of HLA-G than healthy controls, which suggests a possible relevance of this molecule in SLE, it seems not to be related to IL-10 production or disease activity.This study was supported by Fundacion LAIR (8108) and by the Ministerio de Educacion y Cultura (AP2000-2160).Peer reviewe

Trends in Hospital Admissions and Death Causes in Patients with Systemic Lupus Erythematosus: Spanish National Registry

Background: the admission and death causes of SLE patients might have changed over the last years. Methods: Analysis of the Spanish National Hospital Discharge database. All individuals admitted with SLE, according to ICD-9, were selected. The following five admission categories were considered: SLE, cardiovascular disease (CVD), neoplasm, infection, and venous-thromboembolic disease (VTED), along four periods of time (1997&ndash;2000, 2001&ndash;2005, 2006&ndash;2010, and 2011&ndash;2015). Results: The admissions (99,859) from 43.432 patients with SLE were included. The absolute number of admissions increased from 15,807 in 1997&ndash;2000 to 31,977 in 2011&ndash;2015. SLE decreased as a cause of admission (from 47.1% to 20.8%, p &lt; 0.001), while other categories increased over the time, as follows: 5% to 8.6% for CVD, 8.2% to 13% for infection, and 1.4% to 5.5% for neoplasm (p &lt; 0.001 for all). The admission mortality rate rose from 2.22% to 3.06% (p &lt; 0.001) and the causes of death evolved in parallel with the admission categories. A significant trend to older age was observed over time in the overall population and deceased patients (p &lt; 0.001). Conclusions: Better control of SLE over the past two decades has led to a decrease in early admissions, and disease chronification. As a counterpart, CVD, infections, and neoplasm have become the main causes of admissions and mortality

Systemic Autoimmune Diseases in Patients Hospitalized with COVID-19 in Spain: A Nation-Wide Registry Study

We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren&rsquo;s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Beh&ccedil;et&rsquo;s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p &lt; 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78&ndash;1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04&ndash;1.07), heart failure (OR = 1.67, 95% CI 1.10&ndash;2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05&ndash;1.59) and liver disease (OR = 1.97, 95% CI 1.13&ndash;3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis