Targeting B cells in the pre-phase of systemic autoimmunity globally interferes with autoimmune pathology
Anja Werner,
Simon Schäfer,
Olga Zaytseva,
Heike Albert,
Anja Lux,
Jasminka Krištić,
Marija Pezer,
Gordan Lauc,
Thomas Winkler,
Falk Nimmerjahn
Affiliations
Anja Werner
Chair of Genetics, Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erwin-Rommelstr. 3, 91058 Erlangen, Germany
Simon Schäfer
Chair of Genetics, Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erwin-Rommelstr. 3, 91058 Erlangen, Germany
Olga Zaytseva
Genos Ltd, Glycoscience Research Laboratory, Borongajska 83H, 10000 Zagreb, Croatia
Heike Albert
Chair of Genetics, Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erwin-Rommelstr. 3, 91058 Erlangen, Germany
Anja Lux
Chair of Genetics, Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erwin-Rommelstr. 3, 91058 Erlangen, Germany
Jasminka Krištić
Genos Ltd, Glycoscience Research Laboratory, Borongajska 83H, 10000 Zagreb, Croatia
Marija Pezer
Genos Ltd, Glycoscience Research Laboratory, Borongajska 83H, 10000 Zagreb, Croatia
Gordan Lauc
Genos Ltd, Glycoscience Research Laboratory, Borongajska 83H, 10000 Zagreb, Croatia
Thomas Winkler
Chair of Genetics, Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erwin-Rommelstr. 3, 91058 Erlangen, Germany; Medical Immunology Campus Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany
Falk Nimmerjahn
Chair of Genetics, Department of Biology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erwin-Rommelstr. 3, 91058 Erlangen, Germany; Medical Immunology Campus Erlangen, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany; Corresponding author
Summary: Systemic lupus erythematosus (SLE) is characterized by a loss of self-tolerance, systemic inflammation, and multi-organ damage. While a variety of therapeutic interventions are available, it has become clear that an early diagnosis and treatment may be key to achieve long lasting therapeutic responses and to limit irreversible organ damage. Loss of humoral tolerance including the appearance of self-reactive antibodies can be detected years before the actual onset of the clinical autoimmune disease, representing a potential early point of intervention. Not much is known, however, about how and to what extent this pre-phase of disease impacts the onset and development of subsequent autoimmunity. By targeting the B cell compartment in the pre-disease phase of a spontaneous mouse model of SLE we now show, that resetting the humoral immune system during the clinically unapparent phase of the disease globally alters immune homeostasis delaying the downstream development of systemic autoimmunity.