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
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Frontiers in immunology. - 13 (2022) , 1011646, ISSN: 1664-3224
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2022
- Creator
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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
- Rights
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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25.03.2025, 1:43 PM CET
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Associated
- 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
Time of origin
- 2022
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Corrigendum: Do common infections trigger disease-onset or -severity in CTLA-4 insufficiency?
Influences of early-onset infections on the neonatal proteome
Exocrine pancreatic insufficiency
Exocrine pancreatic insufficiency
Intramammary Infections in Heifers—Time of Onset and Associated Risk Factors
Schwerpunktthema Herzinsuffizienz : = Cardiac insufficiency
Cortisol excess and insufficiency
Vitamins in renal insufficiency
Prediction of atrial fibrillation onset and severity using cardiac imaging, blood biomarkers and clinical scores
Recurrent respiratory tract infections (RRTI) in the elderly: a late onset mild immunodeficiency?
Schwerpunktthema Mitralinsuffizienz : = Mitral valve insufficiency
The Medicago truncatula DREPP protein triggers microtubule fragmentation in membrane nanodomains during symbiotic infections
Corrigendum: Do common infections trigger disease-onset or -severity in CTLA-4 insufficiency?
Influences of early-onset infections on the neonatal proteome
Exocrine pancreatic insufficiency
Exocrine pancreatic insufficiency
Intramammary Infections in Heifers—Time of Onset and Associated Risk Factors
Schwerpunktthema Herzinsuffizienz : = Cardiac insufficiency
Cortisol excess and insufficiency
Vitamins in renal insufficiency
Prediction of atrial fibrillation onset and severity using cardiac imaging, blood biomarkers and clinical scores
Recurrent respiratory tract infections (RRTI) in the elderly: a late onset mild immunodeficiency?
Schwerpunktthema Mitralinsuffizienz : = Mitral valve insufficiency