Tubulointerstitial nephritis with IgM-positive plasmacytoid large lymphocyte infiltration in a patient with primary biliary cirrhosis and Sjögren's syndrome.

OBJECTIVES

Adjuvant-induced innate immune responses have been suspected to play a role in the initiation of certain autoimmune disorders. This study investigates the role of alum, an aluminum-based adjuvant in the induction of Sjögren's syndrome-like disorder in mice.

METHODS

Inbred, female New Zealand Mixed (NZM) 2758 strain of mice were injected with alum. Control mice were treated similarly with PBS. The mice were monitored for salivary gland dysfunction by measuring pilocarpine-induced salivation. Presence of lymphocytic infiltrates within the submandibular glands was studied by histopathology. Autoantibodies to Ro and La proteins were analysed by ELISA and the presence of anti-nuclear antibodies (ANA) was analysed by indirect immunofluorescence.

RESULTS

By eight weeks after treatment, the saliva production in the alum-treated mice was significantly decreased in comparison to the PBS-treated mice. This functional loss persisted till the termination of experiments at 20 wks. The incidence and severity of sialoadenitis was significantly higher in the alum-treated mice. Although there were no differences in the levels of anti-Ro/La autoantibodies in sera of alum and PBS-treated groups, the alum group showed higher ANA reactivity.

CONCLUSIONS

In the NZM2758 mice, alum induces a Sjögren's syndrome-like disorder that is characterised by chronic salivary gland dysfunction and the presence of lymphocytic infiltrates within the salivary glands. Thus, the potential of aluminum-based adjuvants for induction of autoimmunity should be closely monitored in individuals genetically susceptible to developing autoimmune disorders.