Cerebral Gray Matter Atrophy Is Associated with the CSF IgG index in African American with Multiple Sclerosis

Abstract

AA patients with MS have lower GM volume and a stronger inverse correlation between GM volume and CSF IgG index, compared to the whites. These findings suggest a potentially prominent role of humoral immunity in mediating tissue injury in AA patients with MS.

Black African and Latino/a identity correlates with increased plasmablasts in MS

“…Several lines of evidence point to a pernicious ectopic humoral response within CNS tissue, likely maintained by CD138 + apoptotic-resistant plasma cells. 12,24,e13 These include the existence of pathogenic autoantibodies, 13,14,25,e14 persistence of intrathecal antibodies despite peripheral CD20 + memory B-cell depletion, 26 and observations of follicle-like aggregates in progressive MS. 27 Our study reveals remarkable trends consistent with, and additive to, previous observations that implicate differential intrathecal humoral responses in patients consistently shown to be at risk of aggressive manifestation of MS. 8,9 We note that although our BALAwMS cohort exhibited an increased disease manifestation, this current study is not powered to assess the clinical differences. Nonetheless, having been conducted using peripheral blood, our work highlights the potential value of this accessible compartment for subsequent research into questions of ethno-ancestry and MS.…”

“…Retrospective chart review implicates the contribution of antibody-secreting cells (ASCs), highlighting a relationship between elevated intrathecal IgG among African American patients with MS relative to Caucasian patients 8 and linking this differential to gray matter atrophy. 9 Indeed, plasmablasts and plasma cells, as ASCs derived from antigen-experienced B cells, appear to be important drivers of both inflammatory 10–12 and neurodegenerative aspects of MS pathogenesis. 9,13,14 ASCs are enriched within the CSF during active gadolinium-enhancing disease, 12 ASC-derived intrathecal IgG correlates with CNS atrophy, 9 and IgM-producing ASCs are associated with aggressive disease course.…”

“…9 Indeed, plasmablasts and plasma cells, as ASCs derived from antigen-experienced B cells, appear to be important drivers of both inflammatory 10–12 and neurodegenerative aspects of MS pathogenesis. 9,13,14 ASCs are enriched within the CSF during active gadolinium-enhancing disease, 12 ASC-derived intrathecal IgG correlates with CNS atrophy, 9 and IgM-producing ASCs are associated with aggressive disease course. 15,e11 The present cross-sectional study therefore investigates whether the peripheral blood of subjects with MS identifying with ethno-ancestral categories more likely to exhibit poorer prognosis reflects an identity-based differential ASC signature.…”

Brain and retinal atrophy in African-Americans versus Caucasian-Americans with multiple sclerosis: a longitudinal study

“…Furthermore, African American patients with systemic lupus erythematous exhibit higher mortality rates (Krishnan and Hubert, 2006), with rheumatoid arthritis show lower rates of remission (Greenberg et al, 2013), and with Graves' disease demonstrate a higher prevalence of thyrotoxicosis (McLeod et al, 2015). African Americans with multiple sclerosis have a higher CSF IgG index than Caucasian American patients, which is inversely correlated with brain volumes (Rinker et al, 2007;Seraji-Bozorgzad et al, 2017). However, the mechanisms underlying the more severe disease course according to race are poorly understood, with several potential factors proposed to possibly play a role including but not limited to genetic variations, gene-gene interactions, differential gene expression (Oksenberg et al, 2004;Huang et al, 2007;Cree et al, 2009), as well as environmental factors (Ascherio and Munger, 2007) such as lower vitamin D levels (Gelfand et al, 2011).…”

An MRI evaluation of grey matter damage in African Americans with MS

“…Retrospective MRI studies have suggested that the more severe course is associated with the higher white matter (WM) lesion load and diffuse microstructural damage in normal appearing WM, rather than greater whole brain and/or grey matter (GM) atrophy 9–11 . However, while all previous studies have been consistent in reporting a higher number of WM lesions in AAs compared to CAs, GM lesions have never been investigated and the findings related to GM atrophy are controversial ranging from no difference to significant decrease in GM global volume and global cortical thickness in AAs and compared to their CAs counterparts 10–12 . To date, a comprehensive analysis of GM involvement in AAs is still lacking, despite the key role of GM focal and diffuse damage in contributing to clinical disability and in driving the extent and pace of MS progression 13–19 .…”