Involvement of Virus-Induced Interferon Production in IgG Autoantibody-Mediated Anemia.

Infection with viruses, such as the lactate dehydrogenase-elevating virus (LDV), is known to trigger the onset of autoimmune anemia through the enhancement of the phagocytosis of autoantibody-opsonized erythrocytes by activated macrophages. Type I interferon receptor-deficient mice show enhanced anemia, which suggests a protective effect of these cytokines, partly through the control of type II interferon production. The development of anemia requires the expression of Fcγ receptors (FcγR) I, III, and IV. Whereas LDV infection decreases FcγR III expression, it enhances FcγR I and IV expression in wild-type animals. The LDV-associated increase in the expression of FcγR I and IV is largely reduced in type I interferon receptor-deficient mice, through both type II interferon-dependent and -independent mechanisms. Thus, the regulation of the expression of FcγR I and IV, but not III, by interferons may partly explain the exacerbating effect of LDV infection on anemia that results from the enhanced phagocytosis of IgG autoantibody-opsonized erythrocytes.

COVID-19 associated with severe autoimmune hemolytic anemia.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) has many known disease associations, including autoimmune, lymphoproliferative, and certain infectious diseases, as well as various medications. Studies have found that severe cases of coronavirus disease 2019 (COVID-19) may be associated with coagulopathies; however, the potential association with AIHA is not clear. CASE REPORT: A patient with no known risk factors or underlying predisposition for developing AIHA presented to a hospital with vague symptoms and profound anemia with a complicated blood bank evaluation. She was found to have COVID-19 and AIHA, for which extensive laboratory testing was performed, including direct antiglobulin tests, elution studies, and cold agglutinin titers, to identify the causative autoantibody. She required multiple blood transfusions and therapeutic interventions before clinical stabilization. DISCUSSION: AIHA is a complex disease with a spectrum of presentations and clinical severity. Many diseases have been associated with a propensity for developing AIHA; however, there are few cases in the literature of patients with COVID-19 and AIHA. Most of the reports involve patients with other underlying conditions that are known to be associated with the development of AIHA. The presentation, clinical findings, and therapeutic interventions in a patient with severe AIHA, without other underlying conditions, in the setting of COVID-19 are discussed. CONCLUSIONS: There are few reports of patients with concurrent COVID-19 and AIHA, and the association is not clear. Although COVID-19 has been shown to be associated with coagulopathies, more research is required to determine whether AIHA may also be a potential complication.

Immune dysregulation and multisystem inflammatory syndrome in children (MIS-C) in individuals with haploinsufficiency of SOCS1.

BACKGROUND: We studied 2 unrelated patients with immune thrombocytopenia and autoimmune hemolytic anemia in the setting of acute infections. One patient developed multisystem inflammatory syndrome in children in the setting of a severe acute respiratory syndrome coronavirus 2 infection. OBJECTIVES: We sought to identify the mechanisms underlying the development of infection-driven autoimmune cytopenias. METHODS: Whole-exome sequencing was performed on both patients, and the impact of the identified variants was validated by functional assays using the patients' PBMCs. RESULTS: Each patient was found to have a unique heterozygous truncation variant in suppressor of cytokine signaling 1 (SOCS1). SOCS1 is an essential negative regulator of type I and type II IFN signaling. The patients' PBMCs showed increased levels of signal transducer and activator of transcription 1 phosphorylation and a transcriptional signature characterized by increased expression of type I and type II IFN-stimulated genes and proapoptotic genes. The enhanced IFN signature exhibited by the patients' unstimulated PBMCs parallels the hyperinflammatory state associated with multisystem inflammatory syndrome in children, suggesting the contributions of SOCS1 in regulating the inflammatory response characteristic of multisystem inflammatory syndrome in children. CONCLUSIONS: Heterozygous loss-of-function SOCS1 mutations are associated with enhanced IFN signaling and increased immune cell activation, thereby predisposing to infection-associated autoimmune cytopenias.