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| Content Provider | frontiers |
|---|---|
| Author | Krausz, Máté Mitsuiki, Noriko Falcone, Valeria Komp, Johanna Posadas-Cantera, Sara Lorenz, Hanns-Martin Litzman, Jiri Wolff, Daniel Kanariou, Maria Heinkele, Anita Speckmann, Carsten Häcker, Georg Hengel, Hartmut Gámez-Díaz, Laura Grimbacher, Bodo |
| 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. |
| ISSN | 16643224 |
| DOI | 10.3389/fimmu.2022.1011646 |
| Volume Number | 13 |
| Journal | Frontiers in Immunology |
| Language | English |
| Publisher Date | 2022-11-02 |
| Access Restriction | Open |
| Subject Keyword | Disease modifiers Inborn errors of immunity (IEI) Immunodeficencies Cytotoxic T-lymphocyte antigen 4 (CTLA4) Immune dysregulaiton |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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