Systemic lupus erythematosus (SLE or lupus) is a chronic, autoimmune disease that can affect multiple organs such as skin, joints, and any visceral organ.

Incidence varies by country, but can range from 1 to 10 per 100,000 people annually, while prevalence is at 20 to 70 per 100,000 annually ⁽¹⁾. Women are more commonly affected than men, with incidence and prevalence rates nearly 10 times that of men. In the United States (US), there is no specific national cost for SLE, but the average hospital charges for diffuse connective tissue diseases, including SLE, was estimated to be about $13.3 billion in 2011.

At presentation, SLE is often mistaken for a myriad of other diseases due to the symptoms of fever, malaise, joint pains, muscle pains and fatigue ⁽²⁾. Differential diagnosis of SLE is challenging, but the presence of anti-nuclear antibodies is the mainstay of diagnositic testing. These antibodies have been shown to react with double stranded DNA (dsDNA), as well as histones. Antibodies to dsDNA are highly specific for SLE, and found in 70% of cases, compared to 0.5% in the population at large ⁽¹⁾. These anti-nuclear antibodies are often seen in skin, where they can form band-like deposits in the basement membrane layer of the epidermis, as wells as labeling the nuclei. Other symptoms of SLE include pleurisy and pericarditis (inflammation of membranes around the heart and lungs) ⁽³⁾, which often accelerates other cardiovascular disease, notably atherosclerosis ⁽⁴⁾. SLE patients often experience muscle and joint pain, possibly associated with ANAs, but generally less debilitating than rheumatoid arthritis ⁽⁵⁾. SLE can also affect the heart, giving rise to a form of endocarditis, the lungs, where it causes a variety of lung disorders, from pneumonitis to pulmonary hypertension, and the kidneys where lupus nephritis can lead to end=stage kidney failure ⁽⁶⁾.

Pharma Models LLC offers a variety of different models of lupus. The classic models of spontaneous lupus comprise of hybrids like the NZB/W F1, MRL/lpr, and BXSB/Yaa. These are hybrids that produce their own versions of lupus-like diseases with symptoms similar to those in human SLE. These include autoantibody production, lymphoid activation and hyperplasia and lupus nephritis.

Induced models of lupus include the pristane-induced model and the chronic graft-versus-host-disease models (cGVHD). Both models oversee a single injection of either pristane or donor cells to rapidly induce lupus-like symptoms. For example, in the cGVHD model, autoantibodies can be detected as early as 10-14 days after induction versus several weeks to months after birth for spontaneous lupus models.

NZB/W F1 model of Lupus

The NZB/W F1 is the oldest classical model of lupus, consisting of the F1 hybrid of the NZB and NZW strains. Both strains exhibit limited autoimmunity, but the F1 hybrid develops severe lupus-like syndrome comparable to that of human lupus patients. They develop lymphadenopathy, splenomegaly, elevated serum antinuclear autoantibodies (ANA), and immune complex-mediated glomerulonephritis (GN) that becomes apparent at 5-6 months, with kidney failure and death at 10-12 months of age. Females are predominantly affected in this model.

MRL/lpr model of Lupus

The MRL/lpr model develops a lupus-like syndrome comprised of lymphadenopathy, brain function deficits, GN, vasculitis, and arthritis. They have high concentrations of circulating autoantibodies such as ANA, anti-ssDNA, anti-dsDNA, anti-Sm, and rheumatoid factors. They display an accelerated mortality rate compared to the NZB/W F1 models, with females dying at 17 weeks of age, males at 22 weeks. Both males and females are affected in this model.

BXSB/Yaa model of Lupus

The BXSB/Yaa model develops a lupus-like syndrome that is much more severe with earlier onset in males. They develop secondary lymphoid tissue hyperplasia, monocytosis, hypergammaglobulinemia, ANA, anti-erythroytic autoantibodies, and immune complex-mediated GN. Mean survival is 5 months in males and 14 months in females.

Pristane-induced model of Lupus

Mice receive intraperitoneal injections of pristane (2, 6, 10, and 14 tetramethylpentadecane, TMPD) in order to induce autoantibodies found in lupus, such as antiribonucleoprotein (RNP) antibodies such as anti-Su, anti-Sm, and anti-U1RNP. Other autoantibodies induced are anti-DNA and anti-histone. The levels of autoantibodies can reach that of MRL/lpr models. Mice treated with pristane are also found to have immune-complex deposition in the kidneys, which leads to severe proteinuria and nephritis. BALB/c strains are widely used, although almost all mouse strains are susceptible to a variable extent. Females are more affected than males in this model.

Induced Chronic Graft-versus-Host Disease (cGVHD) model of Lupus

The cGVHD model is also commonly used, where the mice receive a single injection of donor cells to induce a lupus-like syndrome. cGVHD is induced by injecting DBA CD8+ T cells into BDF1 mice. Severity of the disease correlates with the number of allografted cells. The model produces ANA, lupus-specific autoantibodies, and immune-complex GN. There is rapid disease onset, with autoantibodies being detected 10-14 days after induction versus weeks to months in spontaneous models of lupus. This model is more severe in females ^{(7, 8)}.

Bibliography

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