Arthur Liesz1, Stefan Roth2, Markus Zorn3, Li Sun4, Kerstin Hofmann2, Roland Veltkamp5. 1. Institute for Stroke and Dementia Research, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Germany; Department of Neurology, University Heidelberg, Germany. Electronic address: Arthur.Liesz@med.uni-muenchen.de. 2. Institute for Stroke and Dementia Research, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Germany. 3. Department of Internal Medicine, University Heidelberg, Germany. 4. Department of Neurology, University Heidelberg, Germany. 5. Department of Neurology, University Heidelberg, Germany; Division of Brain Sciences, Imperial College London, UK.
Abstract
BACKGROUND AND PURPOSE: Acute brain injuries induce a systemic immune depression syndrome (SIDS) that predisposes patients to bacterial infections. While cellular compartments of this syndrome have been well characterized, the contribution of humoral immune mechanisms and particularly immunoglobulins to SIDS has not been investigated so far. METHODS: We determined serum immunoglobulin levels and infectious complications at several time points in 159 ischemic and hemorrhagic stroke patients. Additionally, findings were verified in a transient middle cerebral artery occlusion model. A novel immunoassay was established to analyze the IgG excretion ratio in mice. RESULTS: We identified a transient IgG reduction in patients suffering from substantial ischemic or hemorrhagic brain injuries. The IgG-reduction was associated with subsequent bacterial infections. Similarly, transient hypogammaglobulinemia was detected in a murine stroke model. We then used this animal model to further distinguish the mechanism of the IgG reduction by an IgG transfer paradigm. Excretional loss rather than deficient production of IgG was demonstrated to underlay hypogammaglobulinemia. CONCLUSIONS: This is the first report of transient hypogammaglobulinemia after ischemic and hemorrhagic stroke suggesting involvement in infectious complications. These findings pave the road for further studies investigating post-stroke hypogammaglobulinemia as a druggable target for stroke-induced complications.
BACKGROUND AND PURPOSE: Acute brain injuries induce a systemic immune depression syndrome (SIDS) that predisposes patients to bacterial infections. While cellular compartments of this syndrome have been well characterized, the contribution of humoral immune mechanisms and particularly immunoglobulins to SIDS has not been investigated so far. METHODS: We determined serum immunoglobulin levels and infectious complications at several time points in 159 ischemic and hemorrhagic strokepatients. Additionally, findings were verified in a transient middle cerebral artery occlusion model. A novel immunoassay was established to analyze the IgG excretion ratio in mice. RESULTS: We identified a transient IgG reduction in patients suffering from substantial ischemic or hemorrhagic brain injuries. The IgG-reduction was associated with subsequent bacterial infections. Similarly, transient hypogammaglobulinemia was detected in a murinestroke model. We then used this animal model to further distinguish the mechanism of the IgG reduction by an IgG transfer paradigm. Excretional loss rather than deficient production of IgG was demonstrated to underlay hypogammaglobulinemia. CONCLUSIONS: This is the first report of transient hypogammaglobulinemia after ischemic and hemorrhagic stroke suggesting involvement in infectious complications. These findings pave the road for further studies investigating post-stroke hypogammaglobulinemia as a druggable target for stroke-induced complications.
Authors: Mitchell S V Elkind; Amelia K Boehme; Craig J Smith; Andreas Meisel; Marion S Buckwalter Journal: Stroke Date: 2020-09-08 Impact factor: 7.914
Authors: J R Grainger; C B Lawrence; S Krishnan; C O'Boyle; C J Smith; S Hulme; S M Allan Journal: Clin Exp Immunol Date: 2020-12-09 Impact factor: 5.732