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1.
Proc Natl Acad Sci U S A ; 114(4): 734-739, 2017 01 24.
Article in English | MEDLINE | ID: mdl-28057865

ABSTRACT

Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery. We reasoned that the ability of B cells to capture cognate antigen from cell membranes, along with small quantities of coexpressed "bystander" antigens, might enable B-cell escape from tolerance. We tested this hypothesis using influenza hemagglutinin as a model viral antigen and transgenic, MOG-specific B cells. Using flow cytometry and live and fixed cell microscopy, we show that MOG-specific B cells take up large amounts of MOG from cell membranes. Uptake of the antigen from the membrane leads to a strong activation of the capturing B cell. When influenza hemagglutinin is also present in the membrane of the target cell, it can be cocaptured with MOG by MOG-specific B cells via the B-cell receptor. Hemagglutinin and MOG are both presented to T cells, which in turn are activated and proliferate. As a consequence, MOG-specific B cells get help from hemagglutinin-specific T cells to produce anti-MOG antibodies. In vivo, the transfer of MOG-specific B cells into recipient mice after the cocapture of MOG and hemagglutinin leads to the production of class-switched anti-MOG antibodies, dependent on the presence of hemagglutinin-specific T cells. This mechanism offers a link between infection and autoimmunity.


Subject(s)
Antigens, Viral/immunology , Autoantigens/immunology , B-Lymphocytes/immunology , Animals , Autoantibodies/immunology , Autoimmunity/immunology , Cell Line , Cell Membrane/immunology , HEK293 Cells , Hemagglutinin Glycoproteins, Influenza Virus/immunology , Humans , Mice , Mice, Inbred C57BL , Myelin-Oligodendrocyte Glycoprotein/immunology , Receptors, Antigen, B-Cell/immunology , T-Lymphocytes/immunology
2.
Praxis (Bern 1994) ; 111(7): 367-373, 2022.
Article in German | MEDLINE | ID: mdl-35611485

ABSTRACT

Clinical Nutrition for the Medical Patient: From Screening to Diagnosis and Start of Nutritional Therapy Abstract. With the demographic increase of elderly, multimorbid patients, the number of those with disease-related malnutrition is also steadily increasing. We now know that malnutrition is a strong and independent risk factor for morbidity, mortality, and poor quality of life. Fortunately, however, several studies have shown that malnutrition screening followed by physiological nutritional therapy to meet individual nutritional goals has a positive impact on the clinical course of medical patients. In this context, Nutritional Risk Screening is suitable as a tool for assessing nutritive risk in hospitalized and ambulatory patients in family practice. Patients at risk for malnutrition should undergo an in-depth clinical assessment in an interdisciplinary team of nutritionists, nurses, and physicians to clarify the etiology of malnutrition and risk factors, and to examine the indication for nutritional therapy. Such nutrition therapy should be individually tailored to the patient's nutritional needs (calorie, protein, and micronutrient requirements), the underlying disease and the patient's preferences. Patients should be closely monitored, and the therapy should be adapted during the disease.


Subject(s)
Malnutrition , Nutrition Therapy , Aged , Humans , Malnutrition/diagnosis , Malnutrition/etiology , Malnutrition/therapy , Mass Screening , Nutrition Assessment , Nutrition Therapy/adverse effects , Nutritional Status , Nutritional Support/adverse effects , Quality of Life
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