Do common infections trigger disease-onset or -severity in CTLA-4 insufficiency?
Abstract: Purpose: Heterozygous mutations in CTLA4 lead to an inborn error of immunity characterized by immune dysregulation and immunodeficiency, known as CTLA-4 insufficiency. Cohort studies on CTLA4 mutation carriers showed a reduced penetrance (around 70%) and variable disease expressivity, suggesting the presence of modifying factors. It is well studied that infections can trigger autoimmunity in humans, especially in combination with a genetic predisposition.
Methods: To investigate whether specific infections or the presence of specific persisting pathogens are associated with disease onset or severity in CTLA-4 insufficiency, we have examined the humoral immune response in 13 CTLA4 mutation carriers, seven without clinical manifestation and six with autoimmune manifestations, but without immunoglobulin replacement therapy against cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1/2 (HSV 1/2), parvovirus B19 and Toxoplasma gondii. Additionally, we have measured FcγRIII/CD16A activation by EBV-specific IgG antibodies to examine the functional capabilities of immunoglobulins produced by CTLA4 mutation carriers.
Results: The seroprevalence between affected and unaffected CTLA4 mutation carriers did not differ significantly for the examined pathogens. Additionally, we show here that CTLA4 mutation carriers produce EBV-specific IgG, which are unimpaired in activating FcγRIII/CD16A.
Conclusions: Our results show that the investigated pathogens are very unlikely to trigger the disease onset in CTLA-4-insufficient individuals, and their prevalence is not correlated with disease severity or expressivity
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Frontiers in immunology. - 13 (2022) , 1011646, ISSN: 1664-3224
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2022
- Urheber
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Krausz, Máté
Mitsuiki, Noriko
Falcone, Valeria
Komp, Johanna M. A.
Posadas-Cantera, Sara
Lorenz, Hanns-Martin
Litzman, Jiri
Wolff, Daniel
Kanariou, Maria
Heinkele, Anita
Speckmann, Carsten
Häcker, Georg
Hengel, Hartmut
Gámez, Laura
Grimbacher, Bodo
- DOI
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10.3389/fimmu.2022.1011646
- URN
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urn:nbn:de:bsz:25-freidok-2312140
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:43 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Krausz, Máté
- Mitsuiki, Noriko
- Falcone, Valeria
- Komp, Johanna M. A.
- Posadas-Cantera, Sara
- Lorenz, Hanns-Martin
- Litzman, Jiri
- Wolff, Daniel
- Kanariou, Maria
- Heinkele, Anita
- Speckmann, Carsten
- Häcker, Georg
- Hengel, Hartmut
- Gámez, Laura
- Grimbacher, Bodo
- Universität
Entstanden
- 2022
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