Autoimmune disease triggered by infection with alphaproteobacteria

Abstract

Despite having long been postulated, compelling evidence for the theory that microbial triggers drive autoimmunity has only recently been reported. A specific association between Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium, and primary biliary cirrhosis (PBC) has been uncovered in patients with PBC. Notably, the association between Novosphingobium infection and PBC has been confirmed in a mouse model in which infection leads to the development of liver lesions resembling PBC concomitant with the production of anti-PDC-E2 antibodies that cross-react with conserved PDC-E2 epitopes shared by Novosphingobium. The discovery of infectious triggers of autoimmunity is likely to change our current concepts about the etiology of various autoimmune syndromes and may suggest new and simpler ways to diagnose and treat these debilitating diseases.

Figure 1. Classification of bacterial classes and associated clinical phenotypes

*The species that has been shown to be associated with a respective autoimmune disorder. Bacterial classification has been adapted from Systema Naturae [201].

Figure 2. Induction of primary biliary cirrhosis by Novosphingobium due to molecular mimicry?

NKT cells provide help for autoreactive T and B cells, which induce disease by cross-reacting to mammalian and bacterial PDC-E2 enzymes. We are currently investigating the specific role of both cell populations in mediating bile duct damage and their antigen specificity. BCR: B-cell receptor; NKT: Natural killer T cell; PDC-E2: E2 subunit of the pyruvate dehydrogenase complex; TCR: T-cell receptor.