Do Common Infections Trigger Disease-onset or -severity in CTLA-4 Insufficiency?

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 Nov 21

PMID 36405723

Authors

Mate Krausz

Noriko Mitsuiki

Valeria Falcone

Johanna Komp

Sara Posadas-Cantera

Hanns-Martin Lorenz

Jiri Litzman

Daniel Wolff

Maria Kanariou

Anita Heinkele

Carsten Speckmann

Georg Hacker

Hartmut Hengel

Laura Gamez-Diaz

Bodo Grimbacher

Affiliations

Soon will be listed here.

Abstract

Purpose: Heterozygous mutations in lead to an inborn error of immunity characterized by immune dysregulation and immunodeficiency, known as CTLA-4 insufficiency. Cohort studies on 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 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 . Additionally, we have measured FcγRIII/CD16A activation by EBV-specific IgG antibodies to examine the functional capabilities of immunoglobulins produced by mutation carriers.

Results: The seroprevalence between affected and unaffected mutation carriers did not differ significantly for the examined pathogens. Additionally, we show here that 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.

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