Autoimmune anti-DNA and anti-phosphatidylserine antibodies predict development of severe COVID-19.

High levels of autoimmune antibodies are observed in COVID-19 patients but their specific contribution to disease severity and clinical manifestations remains poorly understood. We performed a retrospective study of 115 COVID-19 hospitalized patients with different degrees of severity to analyze the generation of autoimmune antibodies to common antigens: a lysate of erythrocytes, the lipid phosphatidylserine (PS) and DNA. High levels of IgG autoantibodies against erythrocyte lysates were observed in a large percentage (up to 36%) of patients. Anti-DNA and anti-PS antibodies determined upon hospital admission correlated strongly with later development of severe disease, showing a positive predictive value of 85.7% and 92.8%, respectively. Patients with positive values for at least one of the two autoantibodies accounted for 24% of total severe cases. Statistical analysis identified strong correlations between anti-DNA antibodies and markers of cell injury, coagulation, neutrophil levels and erythrocyte size. Anti-DNA and anti-PS autoantibodies may play an important role in the pathogenesis of COVID-19 and could be developed as predictive biomarkers for disease severity and specific clinical manifestations.

Atypical memory B-cells and autoantibodies correlate with anemia during Plasmodium vivax complicated infections.

Malaria caused by Plasmodium vivax is a highly prevalent infection world-wide, that was previously considered mild, but complications such as anemia have been highly reported in the past years. In mice models of malaria, anti-phosphatidylserine (anti-PS) autoantibodies, produced by atypical B-cells, bind to uninfected erythrocytes and contribute to anemia. In human patients with P. falciparum malaria, the levels of anti-PS, atypical B-cells and anemia are strongly correlated to each other. In this study, we focused on assessing the relationship between autoantibodies, different B-cell populations and hemoglobin levels in two different cohorts of P. vivax patients from Colombia, South America. In a first longitudinal cohort, our results show a strong inverse correlation between different IgG autoantibodies tested (anti-PS, anti-DNA and anti-erythrocyte) and atypical memory B-cells (atMBCs) with hemoglobin in both P. vivax and P. falciparum patients over time. In a second cross-sectional cohort, we observed a stronger relation between hemoglobin levels, atMBCs and autoantibodies in complicated P. vivax patients compared to uncomplicated ones. Altogether, these data constitute the first evidence of autoimmunity associating with anemia and complicated P. vivax infections, suggesting a role for its etiology through the expansion of autoantibody-secreting atMBCs.

Presencia de anticuerpos contra neurorreceptores cardiacos de acetilcolina muscarínicos tipo II en pacientes con enfermedad de Chagas e implantación de marcapasos / Presence of antibodies to cardiac neuroreceptors in patients with Chagas disease

Introducción. En diferentes tipos de afecciones cardiacas, incluida la enfermedad de Chagas, se ha descrito la presencia de anticuerpos que reconocen neurorreceptores cardiacos. La respuesta más frecuente es contra receptores de acetilcolina del tipo muscarínico subtipo II (anti-m2MAChR), que reconocen este receptor. Objetivo. El objetivo del presente estudio fue establecer la frecuencia de anticuerpos anti-m2MAChR en un grupo de pacientes cardiópatas con implantación de marcapasos y enfermedad de Chagas. Materiales y métodos. Cincuenta y dos pacientes con enfermedad de Chagas e implantación de marcapasos cardiaco fueron pareados por diagnóstico de implantación con 52 individuos con marcapaso y sin enfermedad de Chagas. La presencia de anticuerpos anti-m2MAChR fue estimada mediante ELISA e inmunoblot. Resultados. El 32,7% de los casos presentaban anticuerpos contra el segundo dominio extracelular del receptor versus 3,8% de los controles (p<0,001). El 51,9% de los casos presentaron anticuerpos contra el tercer dominio intracelular del receptor versus 19,2% de los controles (p<0,001). No se encontraron diferencias clínicas entre los pacientes que presentan y los que no presentan anticuerpos anti-m2MAChR. Conclusión. El odds ratio (OR) del presente estudio muestra una mayor probabilidad de presentar anticuerpos anti-m2MAChR en pacientes con implantación de marcapaso e infección por Trypanosoma cruzi, que en aquéllos con implantación que no presentan infección por el parásito. La presencia de anticuerpos anti-m2MAChR no está relacionada con ningún tipo de manifestación clínica de las evaluadas en este estudio.

Introduction. The presence of antibodies against cardiac neuroreceptors has been established in several kinds of heart diseases as well as in Chagas disease. The antibody type most frequently identified is that which recognizes the muscarinic acetyl choline receptor type II (anti-m2MAChR). Objective. The frequency of the anti-m2MAChR was determined in a group of Colombian patients with permanent pacemaker implantation and Chagas disease. Materials and methods. Fifty-two patients with Chagas disease and permanent heart pacemaker implantation were matched by implantation diagnosis with 52 individuals that required pacemaker, but without Chagas disease. The presence of antibodies that recognized the m2MACh was assessed in the two groups by ELISA and Western blot by using two peptide sequences of the (m2MAChR), the second extracellular domain (2e) and the third intracellular domain (3i). Results. Serological response frequency against 2e-m2MAChR in Chagas patients was 32.7% compared with 3.8% (p<0.01) in the controls; response against 3i-m2MAChR was 51.9% compared with 19.2% (p<0.01) for the controls. No clinical differences were observed between individuals that presented anti-m2MAChR and those who did not. Conclusion. The frequency of anti-m2MAChR was higher in patients with Chagas disease for two of the receptor domains. Furthermore, patients with pacemaker therapy are more likely to have anti-m2MAChR and infection by Trypanosoma cruzi. The anti-m2MAChR response is not associated with any discernable clinical manifestation in this group of patients.

[Presence of antibodies to cardiac neuroreceptors in patients with Chagas disease]. / Presencia de anticuerpos contra neurorreceptores cardiacos de acetilcolina muscarínicos tipo II en pacientes con enfermedad de Chagas e implantación de marcapasos.

INTRODUCTION: The presence of antibodies against cardiac neuroreceptors has been established in several kinds of heart diseases as well as in Chagas disease. The antibody type most frequently identified is that which recognizes the muscarinic acetyl choline receptor type II (anti-m2MAChR). OBJECTIVE: The frequency of the anti-m2MAChR was determined in a group of Colombian patients with permanent pacemaker implantation and Chagas disease. MATERIALS AND METHODS: Fifty-two patients with Chagas disease and permanent heart pacemaker implantation were matched by implantation diagnosis with 52 individuals that required pacemaker, but without Chagas disease. The presence of antibodies that recognized the m2MACh was assessed in the two groups by ELISA and Western blot by using two peptide sequences of the (m2MAChR), the second extracellular domain (2e) and the third intracellular domain (3i). RESULTS: Serological response frequency against 2e-m2MAChR in Chagas patients was 32.7% compared with 3.8% (p<0.01) in the controls; response against 3i-m2MAChR was 51.9% compared with 19.2% (p<0.01) for the controls. No clinical differences were observed between individuals that presented anti-m2MAChR and those who did not. CONCLUSION: The frequency of anti-m2MAChR was higher in patients with Chagas disease for two of the receptor domains. Furthermore, patients with pacemaker therapy are more likely to have anti-m2MAChR and infection by Trypanosoma cruzi. The anti-m2MAChR response is not associated with any discernable clinical manifestation in this group of patients.