Dendritic cells drive profibrotic inflammation and aberrant T cell polarization in systemic sclerosis.

OBJECTIVES: SSc is a devastating autoimmune disease characterized by fibrosis and obliterative vasculopathy affecting the skin and visceral organs. While the processes mediating excessive extracellular matrix deposition and fibroblast proliferation are clear, the exact link between autoimmunity and fibrosis remains elusive. Th17 cells have been proposed as critical drivers of profibrotic inflammation during SSc, but little is known about the immune components supporting their pathogenic role. Our aim was to determine cytokine responses of stimulated monocyte-derived dendritic cells (Mo-DCs) and to determine how they influence T-cell cytokine production in SSc. MATERIAL AND METHODS: Dendritic cells (DCs) activate and shape T cell differentiation by producing polarizing cytokines. Hence, we investigated the cytokine responses of monocyte-derived DCs (Mo-DCs) from patients with limited cutaneous SSc (lcSSc), diffuse cutaneous SSc (dcSSc) and healthy controls (HCs) after stimulation with toll-like receptor (TLR) agonists. Also, using co-culture assays, we analysed T cell subpopulations after contact with autologous TLR-activated Mo-DCs. RESULTS: In general, we observed an increased production of Th17-related cytokines like IL-1ß, IL-17F, IL-21 and IL-22 by SSc compared with HC Mo-DCs, with variations between lcSSc vs dcSSc and early- vs late-stage subgroups. Noticeably, we found a significant increment in IL-33 production by Mo-DCs in all SSc cases regardless of their clinical phenotype. Strikingly, T cells displayed Th2, Th17 and dual Th2-Th17 phenotypes after exposure to autologous TLR-stimulated Mo-DCs from SSc patients but not HCs. These changes were pronounced in individuals with early-stage dcSSc and less significant in the late-stage lcSSc subgroup. CONCLUSIONS: Our findings suggest that functional alterations of DCs promote immune mechanisms favouring the aberrant T cell polarization and profibrotic inflammation behind clinical SSc heterogeneity.

Blood system ABO antigens as risk factor for severity of SARS-CoV-2 infection.

INTRODUCTION: Whether there is an influence of the ABO blood system on SARS-CoV-2 infection is unknown. OBJECTIVE: To analyze if there is an association between the ABO system antigens and susceptibility to and severity of SARS-CoV-2 infection. MATERIAL AND METHODS: The frequency of ABO system antigens was compared in 73 confirmed cases of SARS-CoV-2 infection and 52 clinically healthy donors. Infection severity was assessed by comparing the frequency of antigens by disease severity and mortality. RESULTS: The risk of suffering from SARS-CoV-2 infection increases in subjects with A vs. non-A antigen (OR = 1.45; 95 % CI: 1.061-1.921). Blood phenotype O reduces the risk of SARS-CoV-2 infection (OR = 0.686; 95 % CI: 0.522-0.903). No differences were found regarding disease severity. In critically ill patients, the risk of mortality increased in subjects with A vs. non-A antigen (OR = 3.34; 95 % CI: 1.417-8.159). CONCLUSION: Blood group A is a risk factor for SARS-CoV-2 infection, but not for disease severity, although in critically ill patients it is a risk factor for mortality.

INTRODUCCIÓN: Se desconoce si existe una influencia del sistema sanguíneo ABO en susceptibilidad y gravedad de la enfermedad. OBJETIVO: Analizar si existe una asociación entre los antígenos del sistema ABO y la susceptibilidad y gravedad de la infección por SARS-CoV-2. MATERIAL Y MÉTODOS: Se compararon las frecuencias de los antígenos del sistema ABO en 73 casos confirmados de infección por SARS-CoV-2 y 52 donadores clínicamente sanos. La gravedad de la infección se evaluó comparando la frecuencia de los antígenos por gravedad de la enfermedad y la mortalidad. RESULTADOS: El riesgo de padecer infección por SARS-CoV-2 se incrementa en sujetos con antígeno A vs los no-A (OR=1.45; IC95 %:1.061-1.921). El fenotipo sanguíneo O disminuye el riesgo de padecer infección por SARS-CoV-2 (OR=0.686; IC95 %: 0.522-0.903). No se encontraron diferencias entre la gravedad de la enfermedad. En los pacientes graves, el riesgo de mortalidad se incrementó en sujetos con antígeno A vs los no-A (OR= 3.34; IC95 %: 1.417-8.159). CONCLUSIÓN: El grupo sanguíneo A es un factor de riesgo para padecer infección por SARS-CoV-2, no así en la gravedad de la enfermedad, pero en los pacientes graves fue un factor de riesgo para la mortalidad.

Antígenos del sistema sanguíneo ABO como factor de riesgo para la gravedad de la infección por SARS-CoV-2 / Blood system ABO antigens as risk factor for severity of SARS-CoV-2 infection

Resumen Introducción: Se desconoce si existe una influencia del sistema sanguíneo ABO en susceptibilidad y gravedad de la enfermedad. Objetivo: Analizar si existe una asociación entre los antígenos del sistema ABO y la susceptibilidad y gravedad de la infección por SARS-CoV-2. Material y métodos: Se compararon las frecuencias de los antígenos del sistema ABO en 73 casos confirmados de infección por SARS-CoV-2 y 52 donadores clínicamente sanos. La gravedad de la infección se evaluó comparando la frecuencia de los antígenos por gravedad de la enfermedad y la mortalidad. Resultados: El riesgo de padecer infección por SARS-CoV-2 se incrementa en sujetos con antígeno A vs los no-A (OR=1.45; IC95 %:1.061-1.921). El fenotipo sanguíneo O disminuye el riesgo de padecer infección por SARS-CoV-2 (OR=0.686; IC95 %: 0.522-0.903). No se encontraron diferencias entre la gravedad de la enfermedad. En los pacientes graves, el riesgo de mortalidad se incrementó en sujetos con antígeno A vs los no-A (OR= 3.34; IC95 %: 1.417-8.159). Conclusión: El grupo sanguíneo A es un factor de riesgo para padecer infección por SARS-CoV-2, no así en la gravedad de la enfermedad, pero en los pacientes graves fue un factor de riesgo para la mortalidad.

Abstract Introduction: Whether there is an influence of the ABO blood system on susceptibility to the disease and its severity is unknown. Objective: To analyze if there is an association between the ABO blood system phenotypes and susceptibility to SARS-CoV-2 infection and its severity. Material and methods: The frequency of ABO antigens was compared in 73 confirmed cases of SARS-CoV-2 infection and 52 clinically healthy donors. The severity of the infection was evaluated by comparing the frequency of antigens by severity of the disease and mortality. Results: The risk of SARS-CoV-2 infection is increased in subjects with antigen A vs non-A subjects (OR=1.45; 95 %: 1.061-1.921). Blood phenotype O decreases the risk of SARS-CoV-2 infection (OR= 0.686; 95 % CI: 0.522-0.903). No differences were found regarding disease severity. The mortality risk is increased in subjects antigen A vs non-A (OR= 3.34; 95% IC: 1.417-8.159). Conclusion: Blood group A is a risk factor for SARS-CoV-2 infection, but not for disease severity, although in critically ill patients it is a risk factor for mortality.