Table 1 Phenotypic features of animal models for SJIA and MAS
From: Mouse models of systemic juvenile idiopathic arthritis and macrophage activation syndrome
Repeated TLR-9 stimulation | IL-6 transgenic mice with TLR stimulation | IFN-γ KO/CFA stimulation | IL1RN deficient model | Tsc2 KO model | NSGS mice with xenograft | CD40 stimulation | ||
|---|---|---|---|---|---|---|---|---|
Clinical manifestations | Fever | nd | nd | - | nd | nd | + | nd |
Arthritis | − | nd | + | + | + | nd | nd | |
Skin rash | − | nd | + | nd | nd | nd | nd | |
Splenomegaly | + | nd | + | + | + | + | + | |
Hepatomegaly | + | nd | − | nd | nd | − | nd | |
Lymphadenopathy | nd | nd | + | + | nd | nd | nd | |
Weight loss | + | + | + | nd | nd | + | nd | |
Fatality | − | + | nd | − | − | + | nd | |
Laboratory/pathological manifestations | Leukocytopenia | + (neu↓, Lym↓), myelopoiesis↑ | neu↓ | − (neu↑, lym↓) | − (neu↑, lym → , inflammatory mono↑) | + (neu↓, Lym↓) | + | + (mono↓, lym↓) |
Anemia | + | + | + | + | + | + | nd | |
Thrombocytopenia | + | + (transient) | − (↑) | − (↑) | nd | + | + | |
Hemophagocytosis | + (IL-10 block) | − | + | nd | + | + | + | |
Elevated transaminases | nd (+ in IL18BP − / − mouse) | + | nd | nd | nd | nd | + | |
Hyperferritinemia | + | + | nd | + | + | nd | + | |
sCD25 | nd | ↑ | nd | nd | nd | ↑ | ↑ | |
Lung manifestation | CD4 predominant interstitial infiltration, IFN-γ related inflammation in alveolar macrophages | nd | Neutrophils/activated macrophages dominant infiltration to subpleural/parenchymal area. Augmented IL-1b, IL-6, G-CSF | nd | nd | nd | nd | |
NK cell status | Decreased in spleen, activated | Impaired cytotoxicity | Decreased number, impaired cytotoxicity | nd | nd | nd | Activated | |
Liver pathology | Fibrin thrombi, necrosis, lymphohistiocytic infiltrate | Dilated sinusoids and infiltration of CD68 + macrophage | nd | nd | nd | Macrophage infiltration, loss of hepatic parenchyma | Thrombosis, infarction | |
Cytokines | IL-6 | ↑ | ↑ | ↑ | ↑(plasma, joint mRNA) | nd | ↑ | ↑ |
IL-1β | → | ↑ | ↑ (mRNA levels in LN) | ↑ (serum CXCL1, joint mRNA) | nd | nd | ↑ | |
IL-18 | ↑ | ↑ | ↑ (mRNA levels in LN) | nd | nd | nd | nd | |
IFN-γ | ↑ | CXCL9, 10 ↑ | − | → | nd | → | ↑ | |
Other cytokines | IL-10, IL-12↑ | TNF↑ | IL-17↑ | TNF↑(joint mRNA), S100A8/A9↑ | nd | IL-10, MIP↑ | TNF, IL-12, IL-10↑ | |
Interventions | Protective interventions | IFN-γ blockade (anemia, lung), monomethyl fumarate (cytopenia, IFN-γ, hepatosplenomegaly), rapamycin (cytopenia, hyperferritinemia, hepatosplenomegaly, IFN-γ) | IFN-γ blockade (survival, weight loss, ferritin, ALT, hypercytokinemia) | IL-17 blockade (splenomegaly), IL-12/IL-23p40 blockade (weight loss, arthritis, rash, neutrophilia, hepatosplenomegaly) | Anakinra (neutrophilia, monocytosis, thrombocytosis, hyperferritinemia), phagocyte depletion (splenomegaly, arthritis), rapamycin (leukocytosis, monocytosis, anemia, thrombocytosis, splenomegaly, arthritis) | Rapamycin (hemophagocytosis) | Myeloid cell elimination (anemia, splenomegaly), tocilizumab(life span, anemia, inflammatory cytokines) | Macrophage depletion (ALT, inflammatory cytokines) |
Exacerbating interventions | IL-10R blockade, higher free IL-18 | nd | IL-10 blockade, NK cell depletion (for WT) | nd | nd | nd | nd | |
Reference | [72] | [76] | ||||||