IgG Immune Complexes Break Immune Tolerance of Human Microglia
JOURNAL OF IMMUNOLOGY
Authors: van der Poel, Marlijn; Hoepel, Willianne; Hamann, Jorg; Huitinga, Inge; den Dunnen, Jeroen
Abstract
Microglia are phagocytic cells involved in homeostasis of the brain and are key players in the pathogenesis of multiple sclerosis (MS). A hallmark of MS diagnosis is the presence of IgG Abs, which appear as oligoclonal bands in the cerebrospinal fluid. In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1 beta. We identified Fc gamma RI and Fc gamma RIIa as the two main responsible IgG receptors for the breaking of immune tolerance of microglia. Combined, these data indicate that IgG immune complexes potentiate inflammation by human microglia, which may play an important role in MS-associated inflammation and the formation of demyelinating lesions.
Kinetics of Nucleo- and Spike Protein-Specific Immunoglobulin G and of Virus-Neutralizing Antibodies after SARS-CoV-2 Infection
MICROORGANISMS
Authors: Stroemer, Annabelle; Rose, Ruben; Grobe, Olaf; Neumann, Franziska; Fickenscher, Helmut; Lorentz, Thomas; Krumbholz, Andi
Abstract
Kinetics of neutralizing antibodies and immunoglobulin G (IgG) against the nucleo (N) or spike (S) proteins of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) were studied in patients up to 165 days after PCR diagnosis of infection. Two immunoassays were selected out of eight IgG or total antibody tests by comparing their specificities and sensitivities. Sensitivities were calculated with convalescent sera from 26 PCR-confirmed cases, of which 76.9% had neutralizing antibodies (>1:10). Stored sera collected during the summer 2018 (N = 50) and winter seasons 2018/2019 (N = 50) were included to demonstrate the test specificities. IgG kinetics, avidities, and virus-neutralizing capacities were recorded over up to 165 days in eleven patients and five individuals from routine diagnostics. Sensitivities, specificities, and diagnostic accuracies ranged between 80.8-96.3%, 96.0-100%, and 93.7-99.2%, respectively. Nearly all results were confirmed with two different SARS-CoV-2-specific immunoblots. Six (54.4%) patients exhibited stable N-specific IgG indices over 120 days and longer; three of them developed IgG of high avidity. The S-specific IgG response was stable in ten (91.0%) patients, and eight (72.7%) had neutralizing antibodies. However, the titers were relatively low, suggesting that sustained humoral immunity is uncertain, especially after outpatient SARS-CoV-2 infection.