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

Telesford, Kiel; Kaunzner, Ulrike W.; Perumal, Jai; Gauthier, Susan A.; Wu, Xian; Díaz, Iván; Kruse-Hoyer, Mason; Engel, Casey; Marcille, Melanie; Vartanian, Timothy

doi:10.1212/nxi.0000000000000634

Cited by 14 publications

(19 citation statements)

References 41 publications

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“…CD86 is reported of a high level in circulating CD19 + B cells in septic shock patients than healthy donors, whereas CD80 was lower in survivors than non-survivors at ICU admission. 16 What's more, most circulating ASCs do express high levels of HLA-DR and CD86 in MS. 36 In our study, we also revealed the distinct expression of these co-stimulators in Sep-Pt group, and increased expression of these circulating antigens suggests apoptosis susceptibility may be involved in this immune disorder of disease. By using anti-CD3 antibody, which binds CD3 on surface of T cells, could later stimulate signal and activate T cells.…”

supporting

confidence: 70%

Impaired Circulating Antibody-Secreting Cells Generation Predicts the Dismal Outcome in the Elderly Septic Shock Patients

Xu¹,

Li²,

Zhang³

et al. 2022

JIR

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Purpose Sepsis is a condition that derives from a dysregulated host response to infection. Although B lymphocytes play a pivotal role in immune response, little is known about status of their terminally differentiated cells, antibody-secreting cells (ASCs) during immunosuppressive phase of sepsis, especially in elderly patients. Our aim was to extensively characterize the immune functions of ASCs in elderly septic patients. Patients and Methods Clinical and laboratory data were collected on days 1, 3, and 7 of hospitalization. Circulating ASCs were evaluated by flow cytometry from fresh whole blood in elderly septic patients at the onset of disease. RNA sequencing analyzed ASCs gene expression profile. Receiver operating characteristic (ROC) curve analysis and logistic regression predicted the survival rate of 28-day mortality. Results A total of 103 septic patients were enrolled. The number and proportion of ASCs among total lymphocytes dramatically increased in septic patients, and RNA sequencing analysis showed that ASCs from septic patients exhibited a different gene expression profile. Furthermore, we found these ASCs could promote the function of T cells. Logistic regression analysis showed ASCs population was an independent outcome predictor in septic shock patients. Conclusion Our study revealed the complex nature of immune disorders in sepsis and identified circulating ASCs population as a useful biomarker for predicting mortality in elderly septic patients, which provided a novel clue to combat this severe disease.

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supporting

confidence: 70%

Impaired Circulating Antibody-Secreting Cells Generation Predicts the Dismal Outcome in the Elderly Septic Shock Patients

Xu¹,

Li²,

Zhang³

et al. 2022

JIR

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“…30 Most current DMTs for the treatment of MS do not target the plasmablast and plasma cell subtypes directly (including CD20 B cell depleting agents), 25 a cell subset potentially indicative of more severe MS disease. 31 Despite the sustained decrease of memory B cells and a decrease in CD38 + plasmablasts in the first 12 months of MAGNIFY-MS, serum IgG and IgM levels remained within the normal range over this period. Atacicept, which was shown to target long-lived plasma cells, shows a fast onset of Ig reduction at 4 weeks.…”

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets

Wiendl

Schmierer

Hodgkinson

et al. 2023

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesCladribine tablets cause a reduction in lymphocytes with a predominant effect on B-cell and T-cell counts. The MAGNIFY-MS substudy reports the dynamic changes on multiple peripheral blood mononuclear cell (PBMC) subtypes and immunoglobulin (Ig) levels over 12 months after the first course of cladribine tablets in patients with highly active relapsing multiple sclerosis (MS).MethodsImmunophenotyping was performed at baseline (predose) and at the end of months 1, 2, 3, 6, and 12 after initiating treatment with cladribine tablets. Assessments included lymphocyte subtype counts of CD19+B cells, CD4+and CD8+T cells, CD16+natural killer cells, plasmablasts, and Igs. Immune cell subtypes were analyzed by flow cytometry, and serum IgG and IgM were analyzed by nephelometric assay. Absolute cell counts and percentage change from baseline were assessed.ResultsThe full analysis set included 57 patients. Rapid reductions in median CD19+, CD20+, memory, activated, and naive B-cell counts were detected, reaching nadir by month 2. Thereafter, total CD19+, CD20+, and naive B-cell counts subsequently reconstituted, but memory B cells remained reduced by 93%–87% for the remainder of the study. The decrease in plasmablasts was slower, reaching nadir at month 3. Decrease in T-cell subtypes was also slower and more moderate compared with B-cell subtypes, reaching nadir between months 3 and 6. IgG and IgM levels remained within the normal range over the 12-month study period.DiscussionCladribine tablets induce a specific pattern of early and sustained PBMC subtype dynamics in the absence of relevant Ig changes: While total B cells were reduced dramatically, T cells were affected significantly less. Naive B cells recovered toward baseline, naive CD4 and CD8 T cells did not, and memory B cells remained reduced. The results help to explain the unique immune depletion and repopulation architecture regarding onset of action and durability of effects of cladribine tablets while largely maintaining immune competence.Trial Registration InformationClinicalTrials.govIdentifier:NCT03364036. Date registered: December 06, 2017.

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“…However, there is some evidence of factors that could underlie these disparities. For example, a cross-sectional study of White, Black, and Hispanic pwMS off DMT or on natalizumab compared to healthy controls of matched self-reported racial/ethnic background demonstrated a significant elevation in circulating plasmablasts among Black and Hispanic pwMS compared to White pwMS [ 11 ].…”

Section: Response To Disease Modifying Therapiesmentioning

confidence: 99%

“…Increasing evidence suggests that racial disparities are important factors that may explain differences in the disease course, incidence, prevalence, and outcomes [ 8 ]. Still, Black and Hispanic populations in the United States remain largely underrepresented and understudied in clinical trials [ 9 , 10 , 11 , 12 ]. Recently, a cumulative number of studies have been focusing on improving our understanding of the disease course and disparities across underrepresented populations [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Health Disparities in Multiple Sclerosis among Hispanic and Black Populations in the United States

et al. 2023

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Multiple sclerosis (MS) is an acquired demyelinating disease of the central nervous system (CNS). Historically, research on MS has focused on White persons with MS. This preponderance of representation has important possible implications for minority populations with MS, from developing effective therapeutic agents to understanding the role of unique constellations of social determinants of health. A growing body of literature involving persons of historically underrepresented races and ethnicities in the field of multiple sclerosis is assembling. Our purpose in this narrative review is to highlight two populations in the United States: Black and Hispanic persons with multiple sclerosis. We will review the current understanding about the patterns of disease presentation, genetic considerations, response to treatment, roles of social determinants of health, and healthcare utilization. In addition, we explore future directions of inquiry as well as practical methods of meeting these challenges.

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

Cited by 14 publications

References 41 publications

Impaired Circulating Antibody-Secreting Cells Generation Predicts the Dismal Outcome in the Elderly Septic Shock Patients

Impaired Circulating Antibody-Secreting Cells Generation Predicts the Dismal Outcome in the Elderly Septic Shock Patients

Specific Patterns of Immune Cell Dynamics May Explain the Early Onset and Prolonged Efficacy of Cladribine Tablets

Health Disparities in Multiple Sclerosis among Hispanic and Black Populations in the United States

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