OBJECTIVES: The diagnosis of inclusion body myositis (IBM) can be challenging as it can be difficult to clinically distinguish from other forms of myositis, particularly polymyositis (PM). Recent studies have shown frequent presence of autoantibodies directed against cytosolic 5'-nucleotidase 1A (cN-1A) in patients with IBM. We therefore, examined the autoantigenicity and disease specificity of major epitopes of cN-1A in patients with sporadic IBM compared with healthy and disease controls. METHODS: Serum samples obtained from patients with IBM (n=238), PM and dermatomyositis (DM) (n=185), other autoimmune diseases (n=246), other neuromuscular diseases (n=93) and healthy controls (n=35) were analysed for the presence of autoantibodies using immunodominant cN-1A peptide ELISAs. RESULTS: Autoantibodies directed against major epitopes of cN-1A were frequent in patients with IBM (37%) but not in PM, DM or non-autoimmune neuromuscular diseases (<5%). Anti-cN-1A reactivity was also observed in some other autoimmune diseases, particularly Sjögren's syndrome (SjS; 36%) and systemic lupus erythematosus (SLE; 20%). CONCLUSIONS: In summary, we found frequent anti-cN-1A autoantibodies in sera from patients with IBM. Heterogeneity in reactivity with the three immunodominant epitopes indicates that serological assays should not be limited to a distinct epitope region. The similar reactivities observed for SjS and SLE demonstrate the need to further investigate whether distinct IBM-specific epitopes exist.
- Klíčová slova
- Autoantibodies, Autoimmune Diseases, Dermatomyositis, Polymyositis,
- MeSH
- 5'-nukleotidasa imunologie MeSH
- autoimunitní nemoci imunologie MeSH
- autoprotilátky imunologie MeSH
- dermatomyozitida diagnóza imunologie MeSH
- diabetes mellitus 1. typu imunologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- myozitida s inkluzními tělísky diagnóza imunologie MeSH
- neuromuskulární nemoci imunologie MeSH
- polymyozitida diagnóza imunologie MeSH
- revmatoidní artritida imunologie MeSH
- ROC křivka MeSH
- roztroušená skleróza imunologie MeSH
- senioři MeSH
- senzitivita a specificita MeSH
- Sjögrenův syndrom imunologie MeSH
- studie případů a kontrol MeSH
- systémová sklerodermie imunologie MeSH
- systémový lupus erythematodes imunologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- 5'-nukleotidasa MeSH
- autoprotilátky MeSH
- NT5C1A protein, human MeSH Prohlížeč
Rheumatoid arthritis (RA) is a chronic autoimmune disease with significant morbidity and mortality. Recent studies suggest that modulation of adenosine signaling, a potent immunosuppressive pathway, is a promising approach for treatment of RA. Extracellular adenosine can come from two sources: transport of intracellular adenosine and hydrolysis of extracellular adenine nucleotides by CD73. In this study, we investigated the susceptibility of CD73-deficient C57BL/6 mice to collagen-induced arthritis (CIA), a well-established mouse model of RA. Our data demonstrated that CD73-deficient mice are significantly more susceptible to CIA than wild-type mice. CD73 deficiency resulted in an increased production of proinflammatory cytokines in the joints, increased Th1 T cell responses, and increased joint destruction. Surprisingly, this was accompanied by delayed anticollagen IgG responses, suggesting defective isotype class switching in CD73-deficient mice. Using bone marrow chimera mice, we demonstrated that CD73 expression on nonhematopoietic cells, but not on hematopoietic cells, was important for protection from CIA. We further demonstrated that administration of a selective A2A adenosine receptor agonist to CD73-deficient mice resulted in arthritis incidence similar to wild-type mice in support of a protective role for A2A signaling. Taken together, our study identifies CD73 as an important regulator of CIA in mice. It also strengthens the notion that CD73-generated adenosine by nonhematopoietic cells plays a protective role in RA and suggests that strategies able to enhance CD73 activity or expression levels may be a valid therapeutic option.
- MeSH
- 5'-nukleotidasa nedostatek genetika imunologie MeSH
- adenosin analogy a deriváty farmakologie MeSH
- agonisté adenosinového receptoru A2 farmakologie MeSH
- artritida experimentální genetika imunologie prevence a kontrola MeSH
- CD4-pozitivní T-lymfocyty imunologie metabolismus MeSH
- cytokiny imunologie metabolismus MeSH
- ELISA MeSH
- fenethylaminy farmakologie MeSH
- imunoglobulin G imunologie MeSH
- interferon gama imunologie metabolismus MeSH
- klouby imunologie metabolismus patologie MeSH
- kolagen typ II imunologie MeSH
- kur domácí MeSH
- lymfatické uzliny imunologie metabolismus MeSH
- mediátory zánětu imunologie metabolismus MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- náchylnost k nemoci imunologie MeSH
- odolnost vůči nemocem genetika imunologie MeSH
- ptačí proteiny imunologie MeSH
- Th1 buňky imunologie metabolismus MeSH
- transplantace kostní dřeně MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine MeSH Prohlížeč
- 5'-nukleotidasa MeSH
- adenosin MeSH
- agonisté adenosinového receptoru A2 MeSH
- cytokiny MeSH
- fenethylaminy MeSH
- imunoglobulin G MeSH
- interferon gama MeSH
- kolagen typ II MeSH
- mediátory zánětu MeSH
- ptačí proteiny MeSH