Post-streptococcal auto-antibodies inhibit protein disulfide isomerase and are associated with insulin resistance.

Abstract

Post-streptococcal autoimmunity affects millions worldwide, targeting multiple organs including the heart, brain, and kidneys. To explore the post-streptococcal autoimmunity spectrum, we used western blot analyses, to screen 310 sera from healthy subjects with (33%) and without (67%) markers of recent streptococcal infections [anti-Streptolysin O (ASLO) or anti-DNAse B (ADB)]. A 58 KDa protein, reacting strongly with post-streptococcal sera, was identified as Protein Disulfide Isomerase (PDI), an abundant protein with pleiotropic metabolic, immunologic, and thrombotic effects. Anti-PDI autoantibodies, purified from human sera, targeted similar epitopes in Streptolysin O (SLO, P51-61) and PDI (P328-338). The correlation between post-streptococcal status and anti-human PDI auto-immunity was further confirmed in a total of 2987 samples (13.6% in 530 ASLO positive versus 5.6% in 2457 ASLO negative samples, p<0.0001). Finally, anti-PDI auto-antibodies inhibited PDI-mediated insulin degradation in vitro (n = 90, p<0.001), and correlated with higher serum insulin (14.1 iu/ml vs. 12.2 iu/ml, n = 1215, p = 0.039) and insulin resistance (Homeostatic Model Assessment (HOMA) 4.1 vs. 3.1, n = 1215, p = 0.004), in a population-based cohort. These results identify PDI as a major target of post-streptococcal autoimmunity, and establish a new link between infection, autoimmunity, and metabolic disturbances.

• Authors: Adi Aran, Karin Weiner, Ling Lin, Laurel Ann Finn, Mary Ann Greco, Paul Peppard, Terry Young, Yanay Ofran, Emmanuel Mignot
• Journal: PloS one (PLoS One) Vol. 5 Issue 9 Pg. e12875 (Sep 23 2010) ISSN: 1932-6203 [Electronic] United States
• PMID: 20886095 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Bacterial
• Antigens, Bacterial
• Autoantibodies
• Insulin
• Protein Disulfide-Isomerases

Topics

• Adolescent
• Adult
• Antibodies, Bacterial (immunology)
• Antigens, Bacterial (immunology)
• Autoantibodies (immunology)
• Autoimmunity
• Cohort Studies
• Female
• Humans
• Insulin (blood)
• Insulin Resistance
• Male
• Middle Aged
• Protein Disulfide-Isomerases (immunology)
• Streptococcal Infections (complications, enzymology, immunology)
• Streptococcus (immunology)
• Young Adult