Cell type–specific immune phenotypes predict loss of insulin secretion in new-onset type 1 diabetes

• DOI: 10.1172/jci.insight.125556
• Publication Date: 2019-02-20T16:01:38Z
• Authors: Matthew J. Dufort; Carla J. Greenbaum; Cate Speake; Peter S. Linsley
• Keywords: Adult; Male; 0303 health sciences; Adolescent; Patient Selection; Age Factors; Middle Aged; Prognosis; 3. Good health; Leukocyte Count; 03 medical and health sciences; Diabetes Mellitus, Type 1; Insulin-Secreting Cells; Insulin Secretion; Disease Progression; Leukocytes; Humans; Immunologic Factors; Insulin; Female; Controlled Clinical Trials as Topic; RNA-Seq; Child

The rate of decline in insulin secretion after diagnosis with type 1 diabetes (T1D) varies substantially among individuals and age at diagnosis, but the mechanism(s) behind this heterogeneity are not well understood. We investigated loss pancreatic β cell function new-onset T1D subjects using unbiased whole blood RNA-seq verified key findings by targeted count measurements. found that patients who lost more rapidly had immune phenotypes ("immunotypes") characterized higher levels B cells lower neutrophils, especially neutrophils expressing primary granule genes. neutrophil immunotypes showed strong dependence, particular predicting progression young only. This relationship suggested therapy targeting would be most effective high pretreatment levels, a prediction which was supported data from clinical trial rituximab subjects. These demonstrate link between age-related disease outcome T1D. Furthermore, our suggest greater success could achieved use immunomodulatory specific populations defined characteristics.