Acquired Immunoglobulin G deficiency in stroke patients and experimental brain ischemia

Exp Neurol. 2015 Sep:271:46-52. doi: 10.1016/j.expneurol.2015.04.021. Epub 2015 May 7.

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.

Keywords: IgG deficiency; Immunosuppression; Post-stroke infection; Stroke; Translational research.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Analysis of Variance
  • Animals
  • Biotinylation
  • Brain Injuries / blood
  • Brain Injuries / etiology
  • Disease Models, Animal
  • Female
  • Humans
  • IgG Deficiency / etiology*
  • Immunoglobulin G / blood*
  • Ischemic Attack, Transient / blood
  • Ischemic Attack, Transient / complications
  • Luminescent Measurements
  • Male
  • Mice
  • Middle Aged
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Stroke / blood*
  • Stroke / complications*
  • Stroke / pathology
  • Time Factors

Substances

  • Immunoglobulin G