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Phenotype and oxidative burst of low-density neutrophil subpopulations are altered in common variable immunodeficiency patients

P. Slanina, J. Stichova, V. Bosakova, IS. Zambo, MH. Kohoutkova, P. Laznickova, Z. Chovancova, J. Litzman, T. Plucarova, J. Fric, M. Vlkova

. 2024 ; 106 (2) : 99-112. [pub] 20231123

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc24006975

Grantová podpora
MUNI/A/1098/2022 Lékařská fakulta, Masarykova univerzita
MUNI/A/1244/2021 Lékařská fakulta, Masarykova univerzita
CZ.02.1.01/0.0/0.0/16_019/0000868 Ministerstvo Školství, Mládeže a Tělovýchovy
LX22NPO5107 Ministerstvo Školství, Mládeže a Tělovýchovy
NU21-06-00408 Ministerstvo Zdravotnictví Ceské Republiky
European Social Fund and European Regional Development Fund-ENOCH

Common variable immunodeficiency disorder (CVID) is the most common form of primary antibody immunodeficiency. Due to low antibody levels, CVID patients receive intravenous or subcutaneous immunoglobulin replacement therapy as treatment. CVID is associated with the chronic activation of granulocytes, including an increased percentage of low-density neutrophils (LDNs). In this study, we examined changes in the percentage of LDNs and the expression of their surface markers in 25 patients with CVID and 27 healthy donors (HD) after in vitro stimulation of whole blood using IVIg. An oxidative burst assay was used to assess the functionality of LDNs. CVID patients had increased both relative and absolute LDN counts with a higher proportion of mLDNs compared to iLDNs, distinguished based on the expression of CD10 and CD16. Immature LDNs in the CVID and HD groups had significantly reduced oxidative burst capacity compared to mature LDNs. Interestingly we observed reduced oxidative burst capacity, reduced expression of CD10 after stimulation of WB, and higher expression of PD-L1 in mature LDNs in CVID patients compared to HD cells. Our data indicate that that the functional characteristics of LDNs are closely linked to their developmental stage. The observed reduction in oxidative burst capacity in mLDNs in CVID patients could contribute to an increased susceptibility to recurrent bacterial infections among CVID patients.

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$a Common variable immunodeficiency disorder (CVID) is the most common form of primary antibody immunodeficiency. Due to low antibody levels, CVID patients receive intravenous or subcutaneous immunoglobulin replacement therapy as treatment. CVID is associated with the chronic activation of granulocytes, including an increased percentage of low-density neutrophils (LDNs). In this study, we examined changes in the percentage of LDNs and the expression of their surface markers in 25 patients with CVID and 27 healthy donors (HD) after in vitro stimulation of whole blood using IVIg. An oxidative burst assay was used to assess the functionality of LDNs. CVID patients had increased both relative and absolute LDN counts with a higher proportion of mLDNs compared to iLDNs, distinguished based on the expression of CD10 and CD16. Immature LDNs in the CVID and HD groups had significantly reduced oxidative burst capacity compared to mature LDNs. Interestingly we observed reduced oxidative burst capacity, reduced expression of CD10 after stimulation of WB, and higher expression of PD-L1 in mature LDNs in CVID patients compared to HD cells. Our data indicate that that the functional characteristics of LDNs are closely linked to their developmental stage. The observed reduction in oxidative burst capacity in mLDNs in CVID patients could contribute to an increased susceptibility to recurrent bacterial infections among CVID patients.
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$a Stichova, Julie $u Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic $u Institute of Clinical Immunology and Allergology, St. Anne's University Hospital, Brno, Czech Republic
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$a Bosakova, Veronika $u Center for Translational Medicine, International Clinical Research Center, St Anne's University Hospital Brno, Brno, Czech Republic $u Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic
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$a Litzman, Jiri $u Department of Clinical Immunology and Allergology, Faculty of Medicine, Masaryk University, Brno, Czech Republic $u Institute of Clinical Immunology and Allergology, St. Anne's University Hospital, Brno, Czech Republic
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$a MUNI/A/1098/2022 $p Lékařská fakulta, Masarykova univerzita
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$a MUNI/A/1244/2021 $p Lékařská fakulta, Masarykova univerzita
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$a CZ.02.1.01/0.0/0.0/16_019/0000868 $p Ministerstvo Školství, Mládeže a Tělovýchovy
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$a LX22NPO5107 $p Ministerstvo Školství, Mládeže a Tělovýchovy
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$a NU21-06-00408 $p Ministerstvo Zdravotnictví Ceské Republiky
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$p European Social Fund and European Regional Development Fund-ENOCH
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