Oh, What a Tangled Web We Weave: Decoding the Genetic Enigma of CVID with Autoimmunity

Background: Brace yourselves, folks! We’re diving into the labyrinthine world of common variable immunodeficiency disorder (CVID), where the immune system is as indecisive as a kid in a candy store. But wait, there’s more! Throw in some autoimmunity for extra chaos. Now, let’s play genetic detective with whole genome sequencing (WGS) because, why not?

Methods: We rounded up a bunch of brave souls with CVID and their first-degree kin, extracting their genetic secrets through WGS. Then, we put on our Sherlock Holmes hats to link these genetic breadcrumbs to the clinical mess using high-tech strategies like “sporadic” and “pedigree” analysis. Fancy, right?

Results: We hit the jackpot with 42 blood samples (16 CVID champions and 26 of their cheerleaders). After some serious genetic sifting, we unearthed 9,148 mutations, including 8,171 single-nucleotide variants (SNVs) and 977 Insertion-deletions (InDels). Drumroll, please… We spotlighted 28 genes playing hide-and-seek, with LRBA being the class clown. Lupus was the autoimmune prom queen among our CVID patients. We also took a stroll down the KEGG pathway, discovering the top ten signaling pathways like “primary immunodeficiency” and “JAK-STAT signaling pathway”. Then, because we love a good 3D movie, we used PyMOL to visualize the protein structures of the NFKB1, RAG1, TIRAP, NCF2, and MYB genes. And for the grand finale, we crafted a PPI network that’s like a social media for proteins, connecting our findings with known CVID-related genes from the OMIM database, courtesy of the STRING database.

Conclusion: Spoiler alert: CVID’s genetic plot twist includes both monogenic and oligogenic shenanigans. Our riveting tale suggests that immunodeficiency and autoimmunity might just be two peas in a pod, genetically speaking. And for those keeping score at home, this genetic soap opera has been officially registered with identifier ChiCTR2100044035.