OBJECTIVES: Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice. METHODS: Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n = 101 and n = 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC. RESULTS: All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort. CONCLUSIONS: The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices.

• Klíčová slova
• biomarkers, childhood-onset SLE, clustering analysis, disease activity, gene signatures, interferon, neutrophils, plasma cells,
• MeSH
• dítě MeSH
• genové regulační sítě MeSH
• lidé MeSH
• longitudinální studie MeSH
• shluková analýza MeSH
• systémový lupus erythematodes * MeSH
• transkriptom * MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH

Lupus nephritis (LN) occurs in 50%-60% of patients with childhood-onset systemic lupus erythematosus (cSLE), leading to significant morbidity. Timely recognition of renal involvement and appropriate treatment are essential to prevent renal damage. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative aimed to generate diagnostic and management regimens for children and adolescents with rheumatic diseases including cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of childhood LN. Recommendations were developed using the European League Against Rheumatism standard operating procedures. A European-wide expert committee including paediatric nephrology representation formulated recommendations using a nominal group technique. Six recommendations regarding diagnosis and 20 recommendations covering treatment choices and goals were accepted, including each class of LN, described in the International Society of Nephrology/Renal Pathology Society 2003 classification system. Treatment goal should be complete renal response. Treatment of class I LN should mainly be guided by other symptoms. Class II LN should be treated initially with low-dose prednisone, only adding a disease-modifying antirheumatic drug after 3 months of persistent proteinuria or prednisone dependency. Induction treatment of class III/IV LN should be mycophenolate mofetil (MMF) or intravenous cyclophosphamide combined with corticosteroids; maintenance treatment should be MMF or azathioprine for at least 3 years. In pure class V LN, MMF with low-dose prednisone can be used as induction and MMF as maintenance treatment. The SHARE recommendations for diagnosis and treatment of LN have been generated to support uniform and high-quality care for all children with SLE.

• Klíčová slova
• corticosteroids, disease activity, lupus nephritis, systemic lupus erythematosus, treatment,
• MeSH
• antirevmatika terapeutické užití   MeSH
• azathioprin terapeutické užití   MeSH
• cyklofosfamid terapeutické užití   MeSH
• dítě MeSH
• hormony kůry nadledvin terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• indukce remise metody   MeSH
• kyselina mykofenolová terapeutické užití   MeSH
• lidé MeSH
• management nemoci MeSH
• medicína založená na důkazech normy   MeSH
• nefritida při lupus erythematodes diagnóza   farmakoterapie   MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• věk při počátku nemoci MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• antirevmatika MeSH
• azathioprin MeSH
• cyklofosfamid MeSH
• hormony kůry nadledvin MeSH
• imunosupresiva MeSH
• kyselina mykofenolová MeSH

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, multisystem and potentially life-threatening autoimmune disorder with significant associated morbidity. Evidence-based guidelines are sparse and management is often based on clinical expertise. SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimise and disseminate management regimens for children and young adults with rheumatic diseases like cSLE. Here, we provide evidence-based recommendations for diagnosis and treatment of cSLE. In view of extent and complexity of cSLE and its various manifestations, recommendations for lupus nephritis and antiphospholipid syndrome will be published separately. Recommendations were generated using the EULAR (European League Against Rheumatism) standard operating procedure. An expert committee consisting of paediatric rheumatologists and representation of paediatric nephrology from across Europe discussed evidence-based recommendations during two consensus meetings. Recommendations were accepted if >80% agreement was reached. A total of 25 recommendations regarding key approaches to diagnosis and treatment of cSLE were made. The recommendations include 11 on diagnosis, 9 on disease monitoring and 5 on general treatment. Topics included: appropriate use of SLE classification criteria, disease activity and damage indices; adequate assessment of autoantibody profiles; secondary macrophage activation syndrome; use of hydroxychloroquine and corticosteroid-sparing regimens; and the importance of addressing poor adherence. Ten recommendations were accepted regarding general diagnostic strategies and treatment indications of neuropsychiatric cSLE. The SHARE recommendations for cSLE and neuropsychiatric manifestations of cSLE have been formulated by an evidence-based consensus process to support uniform, high-quality standards of care for children with cSLE.

• Klíčová slova
• Autoantibodies, Corticosteroids, Disease Activity, Systemic Lupus Erythematosus, Treatment,
• MeSH
• dítě MeSH
• lidé MeSH
• medicína založená na důkazech normy   MeSH
• mezinárodní spolupráce MeSH
• mladiství MeSH
• mladý dospělý MeSH
• směrnice pro lékařskou praxi jako téma * MeSH
• systémový lupus erythematodes diagnóza   terapie   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

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

BACKGROUND: Endothelial activation is an important etiopathogenetic factor in a group of disorders characterised by primary or secondary vasculitis. The aim of our study was to determine blood concentrations of von Willebrand factor (vWF), vypustĕno soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in children with various rheumatic diseases and in paediatric controls and to correlate them with clinical and laboratory variables. METHODS AND RESULTS: Total of 28 healthy children (ZD) and 48 patients were evaluated: 6 with systemic lupus erythematosus (SLE), 7 with other diffuse connective tissue diseases (SSD), 11 with Henoch-Schönlein purpura (HSP), 14 with oligoarticular juvenile idiopathic arthritis (JIA) and 10 febrile controls (FC). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and full blood count were recorded. ICAM-1, E-sel and vWF concentrations were measured by sandwich ELISA kits. In SLE patients' concentrations of vWF and ICAM-1 were significantly higher than in healthy (p < 0.05), but not febrile controls. ICAM-1 was significantly increased also in SSD group when compared to healthy children (p < 0.01). Differences in other groups did not reach statistical significance. Significant negative correlation with age was observed for the group as a whole, E-sel correlated with leukocyte and thrombocyte counts (p < 0.01), both molecules with CRP (p < 0.05) and with each other (p < 0.01). CONCLUSIONS: Combined measurement of vWF, ICAM-1 and E-sel as possible markers of endothelial activation in such vypustĕno wide spectrum of paediatric patients and controls is unique vypustĕno. Our finding of increased concentrations of vWF and/or ICAM-1 in children with systemic autoimmune diseases underlines the importance of endothelial involvement in these disorders, but their predictive value in the disease monitoring needs to be further studied.

• MeSH
• biologické markery krev   MeSH
• cévní endotel patofyziologie   MeSH
• dítě MeSH
• E-selektin krev   MeSH
• IgA vaskulitida krev   patofyziologie   MeSH
• juvenilní artritida krev   komplikace   patofyziologie   MeSH
• lidé MeSH
• mezibuněčná adhezivní molekula-1 krev   MeSH
• mladiství MeSH
• předškolní dítě MeSH
• revmatické nemoci krev   komplikace   patofyziologie   MeSH
• systémový lupus erythematodes krev   patofyziologie   MeSH
• vaskulitida krev   komplikace   patofyziologie   MeSH
• von Willebrandův faktor analýza   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• E-selektin MeSH
• mezibuněčná adhezivní molekula-1 MeSH
• von Willebrandův faktor MeSH