Each model has its strengths and limitations in investigating human disease.
#NZB SEARCH OLD FULL#
However, considering the heterogeneity in immunological abnormalities and clinical manifestations of SS, it is not surprising that no single animal model can claim to recapitulate the full spectrum of SS. Thus, to address these issues, several animal model systems have been developed in the past five decades, , ]. Another challenge is to identify how the disease progresses from benign autoimmunity to a fulminant clinical presentation.
Whether a systemic infection, or an exocrine gland infection, or both, are responsible for driving early events in SS is difficult to decipher in patients.
The triggers responsible for initiating autoimmunity in SS remain unclear, but viral infections are considered as the primary candidates. There is a consensus that interactions between a genetically dysregulated immune system and varied environmental stimuli manifest as autoimmune responses in SS. The appearance of circulating autoantibodies several years to decades before the clinical presentation further supports an autoimmune etiology for SS. SS has a strong genetic component and many of the genetic loci associated with SS map to different innate and adaptive immune pathways. There is considerable heterogeneity in the clinical presentation of SS, and this has been a significant obstacle for accurate diagnosis and therapy. Most patients also present with hematological abnormalities, including hypergammaglobulinemia, monoclonal gammopathy, hypocomplementemia, and cytopenias. Other organ systems like the lungs, kidneys, skin, and gastrointestinal tract are affected to varying degrees. Fatigue, arthralgia, arthritis, and peripheral neuropathy are some of the common extraglandular manifestations of SS. The prominent clinical feature of SS is dry mouth and dry eye, caused by the exocrine salivary and lacrimal gland dysfunction. Circulating antibodies targeting intracellular proteins, and immune cells infiltrating different tissues gives SS its autoimmune character. The disease is typically diagnosed in older adults during the fourth or fifth decade of life and shows a strong female to male bias with a ratio of 10:1. Sjögren's syndrome (SS) is one of the three most common systemic rheumatic autoimmune disorders affecting a large number of people worldwide. Therefore, the NZB/W F1 mouse is a powerful tool to decipher pathogenic mechanisms involved in SS related polyautoimmunity and develop appropriate therapeutic strategies. It is plausible that such patients will require distinct therapeutic interventions necessary to treat both SLE and SS. Considering that NZB/W F1 mice also develop a systemic lupus erythematosus (SLE)-like disease, this mouse model mimics the clinical presentation of polyautoimmunity seen in a sizable subset of SS patients. In this review, we provide a historical perspective and detailed description of this mouse model focusing on exocrine gland histopathology, autoantibody populations, and glandular dysfunction. The New Zealand Black (NZB) x New Zealand White (NZW) F1 (NZB/W F1) mouse represents the first spontaneous mouse model of SS. Several animal model systems of SS-like disease have been developed to overcome these issues. Thus, understanding the pathogenic mechanisms involved in the disease process have been a challenge. In addition, the autoimmune response in SS initiates several years before the appearance of clinical symptoms. The clinical findings in SS patients show considerable heterogeneity and overlap with other autoimmune diseases. Sjögren's syndrome (SS) is a chronic rheumatic autoimmune disorder affecting multiple organ systems.
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