IL-14 alpha, the nexus for primary Sjogren's disease in mice and humans

To evaluate the role of interteukin 14 alpha (IL-14a) in Sjogren's syndrome (SS), we evaluated the expression of IL-14a in the peripheral blood lymphocytes (PBL) of patients with primary and secondary SS and normal controls by quantitative RT-PCR. In addition, transgenic IL-14a mice were analyzed from 6 weeks of age to death for both histological and immunological features of Sjogren's disease. Patients with both primary and secondary Sjogren's syndrome expressed IL-14a at statistically higher levels in their peripheral blood compared to normal controls matched for age, sex and ethnic group. Transgenic mice in which IL-14a expression was increased constitutively were previously demonstrated to develop hypergammaglobulinemia, autoantibodies, infiltration of the parotid glands with lymphocytes, mild immune-complex mediated renal disease and large B cell lymphoma. In this paper we expand these observations to demonstrate that these mice develop all. the clinical and immunological features of primary Sjogren's disease in the same relative time frame as patients with primary Sjogren's disease: stage 1-early hypergammaglobulinemia and autoantibody production, stage 2-decreased salivary gland function with early lymphocytic infiltration of the submandibular glands only, but antibody deposition in the submandibular and parotid glands, stage 3-lymphocytic infiltration of the submandibular, parotid and lacrimal glands with B and T lymphocytes and plasma cells along with interstitial lung disease and mild renal disease, and stage 4-large B cell lymphoma. Thus IL-14a is important in the pathophysiology of Sjogren's disease. The IL-14a transgenic mouse is a novel animal model that can be utilized to understand the pathophysiology of Sjogren's disease. (C) 2008 Elsevier Inc. All rights reserved.