Profiling Associations Between IGHG-FCGR Ligand-Receptor Interactions and Disease Progression From Stage 1 and 2 to Stage 3 Type 1 Diabetes.
Lue Ping Zhao, George K Papadopoulos, Jay S Skyler, Hemang M Parikh, William W Kwok, Terry P Lybrand, George P Bondinas, Antonis K Moustakas, Ruihan Wang, Chul-Woo Pyo, Wyatt C Nelson, Daniel E Geraghty, Åke Lernmark
Abstract
Open AccessARTICLE HIGHLIGHTS: This study investigated ligand-receptor interactions (LRIs) between IGHG and FCGR gene products in type 1 diabetes progression. Genes of 1,214 participants from the DPT-1 and TN07 trials were sequenced using next-generation targeted sequencing technology, and LRI associations with the progression time to type 1 diabetes were analyzed using Cox regression modeling. Weak associations were found for IGHG or FCGR variants individually, but multiple LRIs significantly impacted progression. Several IGHG2-FCGR interactions accelerated progression, while a few other IGHG4-FCGR interactions delayed it. The results may provide insights into certain immunogenetic mechanisms of T1D and suggest therapeutic potential of targeting specific LRIs.