Evidence of Intrathecal Immunoglobulin Synthesis in Stroke

Abstract

Background: Immune mechanisms are included in stroke pathophysiologic factors, but the frequency and role of intrathecal antibodies is unclear and diagnostic tests are not routinely performed on cerebrospinal fluid (CSF). Objective: To determine the frequency of intrathecal immunoglobulin synthesis in a well-characterized cohort of patients who experienced "noninflammatory" acute stroke. Design: Retrospective cohort study. Setting: University hospital neurology department. Patients: Patients (n = 318) with stroke who were undergoing lumbar puncture during diagnostic workup and 79 control patients. Results: Cerebrospinal fluid-specific immunoglobulin (IgG, IgM, and IgA) synthesis was significantly (P Ͻ .001) more frequent after stroke (24.8%) compared with the incidence in age-and sex-matched controls (2.5%). Furthermore, 31.3% of stroke patients demonstrated blood-brain barrier dysfunction and 18.1% displayed pleocytosis. Conclusion: The strong association between CSFspecific immunoglobulin synthesis and stroke suggests a role in the development of cerebral ischemia and might constitute an immunologically defined stroke subgroup.

Does B lymphocyte-mediated autoimmunity contribute to post-stroke dementia?

“…Of relevance to stroke recovery, stroke can lead to the intrathecal production of IgG antibodies (Doyle et al, 2015; Pruss et al, 2012b). This is strong evidence that the generation and activation of autoimmune memory B cell responses can occur in the CNS following stroke.…”

“…IgG antibodies are the major isotype found in the blood and are the most versatile antibody isotype, effective at fixing complement, neutralizing toxins and pathogens, and mediating opsonization (Murphy et al, 2012). Significantly, autoantibodies of the IgG, IgM, and IgA isotype have all been detected at an increased frequency in the CSF of stroke patients compared to controls (Pruss et al, 2012b). This indicates that in addition to being activated following stroke, mature B cells may also undergo class switching within the CNS compartment.…”

Antigen Presentation After Stroke

“…Antibodies against brain antigens have been found in CSF of patients with stroke [77,78], suggesting that the release of brain antigens, especially when BBB dysfunction occurs, may be followed by intrathecal B-cell production. The presence of IgG, IgM, and IgA subtypes of autoantibodies has been described [78].…”

“…The presence of IgG, IgM, and IgA subtypes of autoantibodies has been described [78]. Autoantibodies have also been reported in the serum of patients with stroke, including antineurofilament antibodies [79] and antibodies against the N-NR2A/2B subtype of the N-methyl-D-aspartate receptor (NMDAR) [80,81].…”

Antigen-specific immune reactions to ischemic stroke

“…Other researchers have confirmed the presence of specific IgG, IgM and IgA autoantibodies in the CSF (Prüss et al, 2012), and this is often accompanied by pleocytosis and altered albumin quotients of CSF/serum indicating BBB dysfunction. Overall, these findings suggest local activation of the immune system and possibly a pathogenic role of specific autoantibodies in stroke patients.…”