Subgroup of 22q11.2 Deletion Syndrome Patients Have Blood-Borne 16S Bacterial DNA Signatures Associated with Gut Commensals

Background22q11.2 deletion syndrome (22q11.2DS, also known as DiGeorge) affects 1/2,150 individuals. The deletion results in variable clinical phenotypes: thymic hypoplasia or aplasia, hypoparathyroidism, cardiac defects, dysmorphic facial features, and neurodivergent presentations. Vascular leakiness and a compromised blood–brain barrier is also evident in some. The immune consequences of 22q11.2DS are frequent and severe infections. Blood samples from a cohort of 22q11.2DS patients were screened for bacterial DNA signatures. This was assessed in conjunction with their clinical presentations, serum antibody specificities, and cytokine levels relative to normal healthy toddlers.MethodsBlood samples were obtained from a cohort of 22q11.2DS patients (n = 82) along with normal healthy controls (n = 300). Bacterial 16S rRNA DNA sequencing was undertaken. Serum/plasma antibody specificities to pathogen, vaccine, and autoantigens were assessed, and clinical presentations were compiled. 16S sequencing data were analyzed using CLC Genomics microbial Module v25.0. Antibody and cytokine data analysis were performed using GraphPad Prism v10.0ResultsBased on the presence of 16S rRNA DNA signature patterns, the 2q11.2DS cohort was subclustered into 3 major groups. Subcluster 1 comprises bacterial DNA patterns related to the gut commensal species, including species Akkermansia, Allobaculum, Bacteroides, Lactobacillus, Ruminococcus, etc. Interestingly, this cluster was positively correlated with G-tube placement. On the other hand, subcluster 2 had a DNA signature of pathogens such as streptococcal and staphylococcal species. Subcluster 3 had no bacterial DNA. Interestingly, those with a positive gut-commensal pattern had reduced serum cytokine levels relative to subcluster 2. These findings differed significantly with normal healthy 1–4-year-old toddlers, wherein 12% showed a blood-borne DNA signature related to oral commensals and pathogenic species. Data analyses are ongoing, with information regarding antibody responses to various antigens and cytokine profiles being integrated.ConclusionA subset of 22q11.2DS patients have a bacterial DNA pattern in their blood related to species from the gut microbiome. This differed from the bacterial DNA patterns in blood from some “healthy toddler” group, which further differed from that reported for patients with common variable immunodeficiency CVID and acne inversa.