Complement Activation in 22q11.2 Deletion Syndrome

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.Journal of Clinical Immunology (2020) 40:515-523Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Untargeted metabolomic, and proteomic analysis identifies metabolic biomarkers and pathway alterations in individuals with 22q11.2 deletion syndrome

“…More specifically, in this study, we report changes in the complement system cascades and coagulation disruption in 22qDS patients with psychiatric symptoms [Supplementary Table 4b and 5b]. These data are consistent with clinical observations of complement changes in patients with psychiatric symptoms and 22qDS (Grinde et al, 2020 ). There are also clinical reports of patients with 22qDS being comorbid for clotting and coagulation disorders as well (Cohen et al, 2018 ).…”

Severe Hypocalcemia in the Adolescent as the Only Manifestation of <i>22q11</i> Microdeletion Syndrome: Clinical Case

“…По разным статистическим данным, распространенность этого синдрома 1 : 3000-1 : 6000 случаев среди живорожденных, более усредненные цифры частоты встречаемости -это 1 : 4000 [3]. Около 90% случаев данного синдрома являются результатом мутации de novo, но встречаются и семейные случаи, тип наследованияаутосомно-доминантный [2].…”