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

Abstract

Objective: To determine the influence of self-reported Black African and Latin American identity on peripheral blood antibody-secreting cell (ASC) frequency in the context of relapsing-remitting MS.

Methods: In this cross-sectional study, we recruited 74 subjects with relapsing-remitting MS and 24 age-, and self-reported ethno-ancestral identity-matched healthy donors (HDs) to provide peripheral blood study samples. Subjects with MS were either off therapy at the time of study draw or on monthly natalizumab therapy infusions. Using flow cytometry, we assessed peripheral blood mononuclear cells for antibody-secreting B-cell subsets.

Results: When stratified by self-reported ethno-ancestry, we identified significantly elevated frequencies of circulating plasmablasts among individuals with MS identifying as Black African or Latin American relative to those of Caucasian ancestry. Ethno-ancestry-specific differences in ASC frequency were observed only among individuals with MS. By contrast, this differential was not observed among HDs. ASCs linked with poorer MS prognosis and active disease, including IgM⁺- and class-switched CD138⁺ subsets, were among those significantly increased.

Conclusion: The enhanced peripheral blood plasmablast signature revealed among Black African or Latin American subjects with MS points to distinct underlying mechanisms associated with MS immunopathogenesis. This dysregulation may contribute to the disease disparity experienced by patient populations of Black African or Latin American ethno-ancestry.

Figure 1. Subjects with MS self-identifying with Black African or Latin American ethno-ancestry exhibit heightened peripheral blood ASC frequencies

Peripheral blood samples from subjects with MS on natalizumab were stratified according to self-identified ethno-ancestry at risk of more severe MS, CAwMS (n = 27), and BALAwMS (n = 27). Percent frequency of different ASC populations was compared between these cohorts. (A) Representative gating strategy for ASCs; CD27^hi CD38⁺ total ASCs were selected from CD19⁺ cells for downstream phenotypic subset analysis. (B) Representative gates for class-switched IgD⁻ CD27⁺ total ASCs and CD38⁺ CD138⁺ subpopulation. (C) Representative gates for IgM⁺ ASCs. (D and E), Average frequencies of previously described class-switched (D) and IgM⁺ (E) ASC populations; error bars represent SD, p values determined the by 2-sided t test. ASC = antibody-secreting cell; BALAwMS = subjects with MS of Black African or Latin American self-identity; CAwMS = subjects with MS of Caucasian self-identity; NAT = natalizumab therapy.

Figure 2. Ethno-ancestry–based differences in ASC frequency are present among subjects with MS but not HDs

Average frequencies of previously described total CD19⁺(A), class-switched CD19⁺IgD⁻ (B and D) and unswitched CD19⁺IgM⁺ (C and E) ASC populations. CAwMS (n = 8) and BALAwMS (n = 12); CAHD (n = 13) and BALAHD (n = 11). Error bars represent SD, p values determined by the 2-sided t test. ASC = antibody-secreting cell; BALA HD = healthy donors without MS of Black African or Latin American self-identity; BALAwMS = Subjects with MS of Black African or Latin American self-identity; CAwMS = Subjects with MS of Caucasian self-identity; CA HD = healthy donors without MS of Caucasian self-identity.

Figure 3. Numbers of class-switched but not IgM⁺ ASCs are elevated according to ethno-ancestry among subjects with MS

Average number of circulating ASCs for each subject cohort as obtained through event counts derived from flow cytometry gates described prior. Class-switched CD19⁺IgD⁻ ASCs (A); unswitched CD19⁺IgM⁺ ASCs (B). Error bars represent SD, p values determined by the 2-sided t test. ASC = antibody-secreting cell; BALA HD = healthy donors without MS of Black African or Latin American self-identity; BALAwMS = Subjects with MS of Black African or Latin American self-identity; CAwMS = Subjects with MS of Caucasian self-identity; CA HD = healthy donors without MS of Caucasian self-identity; NAT = natalizumab therapy.