The CD40 × LMP1 Hypothesis in Graves' Disease

The CD40 × LMP1 Hypothesis in Graves' Disease. An integrated analysis of genetic susceptibility, immune dysfunction, and Epstein-Barr virus in autoimmune thyroid disease. Analysis date: 31 May 2026. Data sources: PRJNA1198793 (RNA-Seq, n=12), GSE71956 (T cell microarray, n=31), GSE285196 (scRNA-seq B cells). This preprint presents a convergent model incorporating Epstein-Barr virus (EBV) as the mechanistic thread connecting genetic susceptibility, immune dysfunction, and clinical phenotype in AITD. The central hypothesis is that EBV simultaneously disables CD8-mediated control through viral immune evasion mechanisms, hijacks B cell activation through latent proteins (EBNA2, LMP1), and drives the inflammatory loop that sustains disease activity. Without EBV, core phenomena in AITD lack a mechanistic framework linking genetic risk to immune pathology.