Association of IDDM and Attenuated Response of 2′,5′-Oligoadenylate Synthetase to Yellow Fever Vaccine

Abstract

Basal and yellow fever vaccination-induced 2′,5′-oligoadenylate synthetase (2′,5′A) activity was determined in blood mononuclear cells (peripheral blood lymphocytes [PBLs]) from insulin-dependent diabetes mellitus (IDDM) and matched control subjects. The live attenuated yellow fever vaccine represented a primary stimulus in all subjects. First, basal 2′,5′A activity increased severalfold in response to yellow fever vaccination. In IDDM subjects, this increase was significantly lower (P = .025). Second, the 2′,5′A activity increased proportionately to the higher basal 2′,5′A activity in IDDM subjects. In control subjects, the increase in 2′,5′A activity was not dependent on the basal activity. There was no relationship between basal or stimulated 2′,5′A activity and age, sex, duration of IDDM, age at onset of IDDM, metabolic control, or HLA-DQ β-chain gene polymorphism. There is a direct relationship between 2′,5′A activity and latent viral infections associated with the presence of double-stranded RNA and with cellular interferons (IFNs) formed in response to viral infections. The higher basal 2′,5′A activity (P = .05) in relation to the stimulated activity may therefore signify a latent infection or the presence of double-stranded RNA in PBLs of IDDM subjects. In Vitro stimulation of PBLs showed increased IFN sensitivity in IDDM subjects. Analysis of 2′,5′A activity is proposed to be a sensitive measure of the activation of the IFN system and the level of latent infectivity.