Table 3 Differences in the pathogenesis between oligoarticular, polyarticular rheumatoid factor (RF)-negative and positive, systemic (sJIA), psoriatic arthritis and enthesitis-related arthritis (ERA). As an autoinflammatory disease sJIA is different in pathogenesis, clinical manifestations, and therapeutic strategy compared to non-systemic subtypes of JIA. ANA - Antinuclear antibodies, anti-MCV - antibodies against mutated citrullinated vimentin, anti-CCP - anti-cyclic citrullinated peptide, IL - interleukin, MIF - macrophage migration inhibitory factor, PsJIA – psoriatic JIA, RF – rheumatoid factor, sJIA – systemic JIA, TNF - tumour necrosis factor
From: Juvenile idiopathic arthritis: from aetiopathogenesis to therapeutic approaches
| Â | Oligoarticular JIA | Polyarticular JIA | ERA | Psoriatic JIA | sJIA |
|---|---|---|---|---|---|
Type of disease | Autoimmune | Autoimmune | Autoimmune | Early-onset PsJIA – autoimmune, while late-onset PsJIA – autoinflammatory | Autoinflammatory |
Immune system mainly involved in pathogenesis | Adaptive immune system | Adaptive immune system | Adaptive immune system | Adaptive immune system in early-onset PsJIA Innate immune response in late-onset PsJIA | Innate immune system |
Gene association | MHC class II | MHC class II | HLA-B27 | HLA-B/C, HLAB, IL12B, IL23R, TNP1, TRAF3IP3, REL HLA-B27 in late-onset PsJIA | TNF, IL6, IL10, MIF, IL1 |
Antibodies | ANA | ANA RF, anti-CCP, anti-MCV – for RF+ JIA | ANA may be positive in some cases | ANA in the early-onset PsJIA | – |
Predominant effector cells | CD4+, CD8+ T-cells, neutrophils | CD4+, CD8+ T-cells | γδT-cells, Th17 cells | Th1 and Th17 cells subsets, macrophages | Monocytes, macrophages, neutrophils |
Key moment in pathogenesis | Imbalance between inflammatoryTh1/Th17 and Treg cells | Imbalance between pro-inflammatory Th1/Th17 and Treg cells | HLA-B27 involved in presentation of unidentified arthritogenic peptide caused T-cells activation and induction of endoplasmic reticulum stress | Autoinflammatory activation at the synovial-entheseal complex Autoimmune processes in extra-articular tissues | Abnormal activation of phagocytes leads to hypersecretion of pro-inflammatory cytokines |
Main pro-inflammatory cytokines | TNFα, IL17, IFNγ | TNFα, IL17, IL33, IFNγ | TNFα, IL17, IL23 | IL17, IL23 | IL1, IL6, IL18, IL37, LRG and ADA2 |
Main treatment targets | Inhibition of T-cell proliferation, rarely anti-TNFα therapy is needed | Inhibition of T-cell proliferation, block of TNFα | Block of TNFα | Inhibition of T-cell proliferation, block of TNFα | Block of IL1 and IL6 signalling pathway |