Complement Activation in 22q11.2 Deletion Syndrome

Dina Grinde,Torstein Øverland,Tore G Abrahamsen,Tom Eirik Mollnes,Kari Lima,Camilla Schjalm

doi:10.1007/s10875-020-00766-x

Abstract

The 22q11.2 deletion syndrome (22q11.2 del), also known as DiGeorge syndrome, is a genetic disorder with an estimated incidence of 1:3000 to 1:6000 births. These patients may suffer from affection of many organ systems with cardiac malformations, immunodeficiency, hypoparathyroidism, autoimmunity, palate anomalies, and psychiatric disorders being the most frequent. The importance of the complement system in 22q11.2 del has not been investigated. The objective of this study was to evaluate the complement system in relation to clinical and immunological parameters in patients. A national cohort of patients (n = 69) with a proven heterozygous deletion of chromosome 22q11.2 and a group of age and sex matched controls (n = 56) were studied. Functional capacity of the classical, lectin, and alternative pathways of the complement system as well as complement activation products C3bc and terminal complement complex (TCC) were accessed and correlated to clinical features. All patients in our study had normal complement activation in both classical and alternative pathways. The frequency of mannose-binding lectin deficiency was comparable to the normal population. The patients had significantly raised plasma levels of C3bc and a slight, but not significant, increase in TCC compared with controls. This increase was associated with the presence of psychiatric disorders in patients. The present study shows no complement deficiencies in 22q11.2 deletion syndrome. On the contrary, there are signs of increased complement activation in these patients. Complement activation is particularly associated with the presence of psychiatric disorders.

Highlights

The 22q11.2 deletion syndrome (22q11.2 del), known as DiGeorge or velocardiofacial syndrome, is the most common microdeletion syndrome in humans with an estimated prevalence from 1:3000 to 1: 6000 live births [1]
In order to address if these patients had pathologic in vivo complement activation, we studied the complement activation products C3bc and terminal complement complex (TCC)
We investigated the complement system in patients with 22q11.2 del compared with controls

Summary

Introduction

The 22q11.2 deletion syndrome (22q11.2 del), known as DiGeorge or velocardiofacial syndrome, is the most common microdeletion syndrome in humans with an estimated prevalence from 1:3000 to 1: 6000 live births [1]. Due to clinical variability and heterogeneity, the occurrence of the disorder may be underestimated [2]. The prevalence is expected to rise due to improved patient survival [1]. In 22q11.2 del, most of the patients have a typical 3 megabase (Mb) deletion on the long arm of chromosome 22 containing over 30 different genes. The inheritance of the syndrome is autosomal dominant, but 90% of cases appear to be de novo [3, 4]. The phenotype variation is large, and syndrome presentation includes immunodeficiency of variable severity, congenital heart defects, hypoparathyroidism, velopharyngeal insufficiency

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