Correlation of blood TCR repertoire with an organ manifestation in a mouse model of autoimmune disease

One hallmark of some autoimmune diseases is the individual variability of symptoms. Organs affected by the disease differ between patients, making diagnosis of affected organs a challenge. Although numerous studies have investigated the correlation between T cell antigen receptor (TCR) repertoires and development of infectious and immune diseases, the correlation between TCR repertoires and variations in disease symptoms among individuals remains unclear. This study investigated correlation of TCR repertoires in blood T cells with severity of an autoimmune phenotype that varies among individuals. We sequenced TCR repertoires in the blood and stomachs of mice deficient in autoimmune regulator (Aire) (AIRE KO), a mouse model of human autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Data analysis revealed that degree of similarity in TCR repertoires between the blood and stomach differs among individual AIRE KO mice and reflects the severity of stomach inflammation. This suggests the existence of blood TCR repertoires that can be used to predict affected organs. Indeed, we identified a set of TCR sequences whose frequencies in blood correlated with severity of stomach manifestations. Our results highlight the potential of using TCR repertoires not just for diagnosis of disease development, but also for diagnosis of affected organs in autoimmune diseases.