Informace o publikaci
Do common infections trigger disease-onset or -severity in CTLA-4 insufficiency?
| Autoři | |
|---|---|
| Rok publikování | 2022 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | Frontiers in immunology |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1011646/full |
| Doi | http://dx.doi.org/10.3389/fimmu.2022.1011646 |
| Klíčová slova | cytotoxic T-lymphocyte antigen 4 (CTLA-4); immunodeficencies; immune dysregulation; inborn errors of immunity (IEI); disease modifiers |
| Popis | 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 Fc?RIII/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 Fc?RIII/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. |