The value of animal models to study immunopathology of primary human Sjögren's syndrome symptoms

Abstract

Sjögren’s syndrome (SjS) is a complex chronic autoimmune disease of multifactorial etiology that results in eventual loss of secretory function in the exocrine glands. The challenges towards finding a therapeutic prevention or treatment for SjS are due primarily to a lack of understanding in the pathophysiological and clinical progression of the disease. In order to circumnavigate this problem, there is a need for appropriate animal models that resemble the major phenotypes of human SjS and deliver a clear underlying biological or molecular mechanism capable of defining various aspects for the disease. Here, we present an overview of SjS mouse models that are providing insight into the autoimmune process of SjS and advance our focus on potential diagnostic and therapeutic targets.

Systemic manifestations of primary Sjögren's syndrome in the NOD.B10Sn-H2/J mouse model

“…As is the case for many complex pathoses, there is a pressing need for good animal models that recapitulate findings in humans in order to understand disease progression and to design targeted therapeutics. This is particularly true for SS, as early disease markers, staging criteria, and therapeutics are lacking [2]. Our findings indicate that NOD.B10 mice are ideally suited for the study of SS, as they develop robust sialadenitis and dacryoadenitis.…”

“…In secondary SS (sSS) patients also have an additional autoimmune connective tissue disease. While studies in human subjects are critical to evaluate disease mechanisms and validate therapeutic targets, work in mouse models is equally valuable, as it allows for initial pathway discovery and interventional studies that are not currently possible in pSS patients [2]. …”

Multiple Roles for B-Lymphocytes in Sjogren’s Syndrome

“…Various models have been used, including the MRL/lpr mouse, which carries a mutation in the fas gene and reproduces the human lymphoproliferative syndrome; the NOD mouse, which developed spontaneous diabetes along with SS; the B6.NOD-Aec1Aec2 mouse, which carries genetic regions from the NOD mouse that predisposes C57BL/6J mice to develop SS without diabetes; the BAFF transgenic mouse, which develops proliferative glomerulonephritis along with SS; and the IL-14α transgenic mouse, which develops all the features of SS seen in patients in the same relative time frame, including hypergammaglobulinemia, autoantibodies, salivary and lacrimal gland hypo-function, lymphocytic pneumonitis, renal disease and lymphoma [32,33,34,35,36,37]. Interestingly, increased expression of IL-14α has been noted in patients with SS [36], as well as in MRL/lpr, NOD and B6.NOD-Aec1Aec2 mice (unpublished data).…”

What can Sjögren's syndrome-like disease in mice contribute to human Sjögren's syndrome?

“…As a result, to study the pathophysiological and immunological nature of this autoimmune disease, numerous mouse models have been developed that presumably mimic specific characteristics common to the human disease. The potential relevance of these mouse lines, along with the genetic bases for their disease phenotypes, are discussed in detail in several recent reviews [15,16]. Nevertheless, there remain serious concerns that these SS-like models are often artificial, exhibit at best only partial disease, and do not sufficiently represent the clinical human disease.…”