Dissection of the Pre-Germinal Center B-Cell Maturation Pathway in Common Variable Immunodeficiency Based on Standardized Flow Cytometric EuroFlow Tools

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F21%3A00074575" target="_blank" >RIV/00159816:_____/21:00074575 - isvavai.cz</a>

Alternative codes found

RIV/00064203:_____/21:10425455 RIV/00216208:11130/21:10425455 RIV/00216224:14110/21:00121774

Result on the web

<a href="https://www.frontiersin.org/articles/10.3389/fimmu.2020.603972/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fimmu.2020.603972/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fimmu.2020.603972" target="_blank" >10.3389/fimmu.2020.603972</a>

Result language

angličtina

Original language name

Dissection of the Pre-Germinal Center B-Cell Maturation Pathway in Common Variable Immunodeficiency Based on Standardized Flow Cytometric EuroFlow Tools

Original language description

Introduction Common Variable Immunodeficiency (CVID) is characterized by defective antibody production and hypogammaglobulinemia. Flow cytometry immunophenotyping of blood lymphocytes has become of great relevance for the diagnosis and classification of CVID, due to an impaired differentiation of mature post-germinal-center (GC) class-switched memory B-cells (MBC) and severely decreased plasmablast/plasma cell (Pb) counts. Here, we investigated in detail the pre-GC B-cell maturation compartment in blood of CVID patients. Methods In this collaborative multicentric study the EuroFlow PID 8-color Pre-GC B-cell tube, standardized sample preparation procedures (SOPs) and innovative data analysis tools, were used to characterize the maturation profile of pre-GC B-cells in 100 CVID patients, vs 62 age-matched healthy donors (HD). Results The Pre-GC B-cell tube allowed identification within pre-GC B-cells of three subsets of maturation associated immature B-cells and three subpopulations of mature naive B-lymphocytes. CVID patients showed overall reduced median absolute counts (vs HD) of the two more advanced stages of maturation of both CD5(+) CD38(+/++) CD21(het) CD24(++) (2.7 vs 5.6 cells/mu l, p=0.0004) and CD5(+) CD38(het) CD21(+) CD24(+) (6.5 vs 17 cells/mu l, p&lt;0.0001) immature B cells (below normal HD levels in 22% and 37% of CVID patients). This was associated with an expansion of CD21(-)CD24(-) (6.1 vs 0.74 cells/mu l, p&lt;0.0001) and CD21(-)CD24(++) (1.8 vs 0.4 cells/mu l, p&lt;0.0001) naive B-cell counts above normal values in 73% and 94% cases, respectively. Additionally, reduced IgMD(+) (21 vs 32 cells/mu l, p=0.03) and IgMD(-) (4 vs 35 cells/mu l, p&lt;0.0001) MBC counts were found to be below normal values in 25% and 77% of CVID patients, respectively, always together with severely reduced/undetectable circulating blood pb. Comparison of the maturation pathway profile of pre-GC B cells in blood of CVID patients vs HD using EuroFlow software tools showed systematically altered patterns in CVID. These consisted of: i) a normally-appearing maturation pathway with altered levels of expression of &gt;1 (CD38, CD5, CD19, CD21, CD24, and/or smIgM) phenotypic marker (57/88 patients; 65%) for a total of 3 distinct CVID patient profiles (group 1: 42/88 patients, 48%; group 2: 8/88, 9%; and group 3: 7/88, 8%) and ii) CVID patients with a clearly altered pre-GC B cell maturation pathway in blood (group 4: 31/88 cases, 35%). Conclusion Our results show that maturation of pre-GC B-cells in blood of CVID is systematically altered with up to four distinctly altered maturation profiles. Further studies, are necessary to better understand the impact of such alterations on the post-GC defects and the clinical heterogeneity of CVID.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2021

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Frontiers in Immunology

ISSN

1664-3224

e-ISSN

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Volume of the periodical

11

Issue of the periodical within the volume

FEB 11

Country of publishing house

CH - SWITZERLAND

Number of pages

14

Pages from-to

603972

UT code for WoS article

000624523100001

EID of the result in the Scopus database

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