BACKGROUND: B-cell activating factor of the tumour necrosis factor family (BAFF) plays a role in autoantibody production and is elevated in dermatomyositis (DM) and anti-Jo-1-positive polymyositis (PM). We investigated the inter-relationships between serum levels of BAFF, anti-Jo-1 autoantibodies, and disease activity. METHODS: Serum levels of BAFF and anti-Jo-1 antibodies measured by enzyme-linked immunosorbent assay (ELISA) were compared to levels of myoglobin, creatine kinase (CK), aminotransferases (alanine (ALT) and aspartate (AST)), C-reactive protein (CRP), and disease activity assessed by the Myositis Disease Activity Assessment Tool in 63 anti-Jo-1 antibody-positive DM/PM patients. Serial serum samples collected at 2 (46 cases) and 3-5 time points (23 cases) were included. Relationships between BAFF, anti-Jo-1, disease activity, CRP, and their longitudinal changes were evaluated using correlation analysis, multiple regression (MR), path analysis (PA), and hierarchical linear models (HLM). RESULTS: Cross-sectional assessment demonstrated significant correlations between the levels of BAFF and anti-Jo-1 antibodies which were associated with levels of CK, myoglobin, AST, and CRP, as well as multivariate associations between BAFF, anti-Jo-1 antibodies, and CK levels. PA revealed direct effects of anti-Jo-1 antibodies on CK (β = 0.41) and both direct (β = 0.42) and indirect (through anti-Jo-1 antibodies; β = 0.17) effects of BAFF on CK. Changes in levels of both BAFF and anti-Jo-1 between two time points (Δ) were associated with Δmyoglobin and Δaminotransferases and changes of BAFF correlated with ΔCK, Δcutaneous, Δmuscle, Δglobal, and Δskeletal disease activities. The longitudinal analysis showed a high intra-individual variability of serum levels of BAFF over time (97%) which could predict 79% of the variance in anti-Jo-1 levels. The anti-Jo-1 variability was explained by inter-individual differences (68%). The close longitudinal relationship between levels of BAFF, anti-Jo-1, and disease activity was supported by high proportions of their variance explained with serum levels of CK and CRP or pulmonary and muscle activities. CONCLUSION: Our findings of associations between levels of BAFF and anti-Jo-1 antibodies in serum and myositis activity suggest a role of this cytokine in disease-specific autoantibody production as part of disease mechanisms, and support BAFF as a potential target for intervention in anti-Jo-1-positive myositis patients.

• MeSH
• antinukleární protilátky krev   MeSH
• dermatomyozitida krev   imunologie   patologie   MeSH
• dospělí MeSH
• faktor aktivující B-buňky krev   MeSH
• histidin-tRNA-ligasa imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• průřezové studie MeSH
• senioři 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

Dizertační práce, která se zaměřila na výzkum idiopatických zánětlivých myopatií a roli BAFF, interferonu alfa, visfatinu a autoprotilátek.

• MeSH
• autoprotilátky MeSH
• faktor aktivující B-buňky MeSH
• fenotyp MeSH
• imunologické testy MeSH
• interferon alfa MeSH
• messenger RNA MeSH
• myozitida MeSH
• nikotinamidfosforibosyltransferasa MeSH
• receptor faktoru aktivujícího B-buňky MeSH
• Publikační typ
• vysokoškolské kvalifikační práce MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• alergologie a imunologie
• ortopedie

• MeSH
• ANCA-asociované vaskulitidy diagnóza   farmakoterapie   MeSH
• antirevmatika terapeutické užití   MeSH
• B-lymfocyty účinky léků   fyziologie   MeSH
• biomarkery farmakologické MeSH
• dospělí MeSH
• faktor aktivující B-buňky genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocytární deplece MeSH
• regulační oblasti nukleových kyselin genetika   MeSH
• rituximab terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• dopisy MeSH
• práce podpořená grantem MeSH

• MeSH
• cyklické S-oxidy terapeutické užití   MeSH
• cytokiny imunologie   MeSH
• faktor aktivující B-buňky * imunologie   MeSH
• humanizované monoklonální protilátky terapeutické užití   MeSH
• imunologické faktory terapeutické užití   MeSH
• imunosupresiva terapeutické užití   MeSH
• interferon alfa * imunologie   MeSH
• interleukin-17 * imunologie   MeSH
• interleukin-6 * imunologie   MeSH
• isochinoliny terapeutické užití   MeSH
• Janus kinasy imunologie   MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   MeSH
• objevování léků MeSH
• piperidiny MeSH
• pyrazoly terapeutické užití   MeSH
• pyrimidiny terapeutické užití   MeSH
• rekombinantní fúzní proteiny terapeutické užití   MeSH
• rituximab terapeutické užití   MeSH
• schvalování léčiv MeSH
• signální transdukce * imunologie   MeSH
• systémový lupus erythematodes * farmakoterapie   imunologie   MeSH
• transkripční faktory STAT imunologie   MeSH
• tyrosinkinasy imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

INTRODUCTION: Belimumab is a fully humanised mAb against B lymphocyte stimulator (B-LyS). It is the first biological drug licensed and approved by the US FDA and the European Medicines Agency (EMA) for use in combination with standard immunosuppressants in autoantibody-positive systemic lupus erythematosus (SLE). Areas covered: This manuscript evalues the recent data concerning belimumab's safety and clinical effectiveness and its current place in the treatment of SLE. This includes an overview of the recent data coming from the post-hoc analyses of the BLISS trials, real-life experience with belimumab and the accumulating data on its safety. Attention is also paid to the progress made in the identification of predictors of response to belimumab, recent phase I/II/III studies with subcutaneous belimumab, and experience with B cell modulation coming from recent trials with other B cell modulating drugs. Expert opinion: Belimumab currently has its established role in the treatment of patients with SLE with serologic activity and clinical activity namely in mucocutaneous and musculoskeletal domains despite standard of care treatment. Better identification of patients who can benefit from treatment with belimumab is warranted. Data from ongoing studies in lupus nephritis and other data from observational studies are eagerly awaited.

• MeSH
• antinukleární protilátky krev   MeSH
• faktor aktivující B-buňky imunologie   MeSH
• humanizované monoklonální protilátky škodlivé účinky   imunologie   terapeutické užití   MeSH
• klinické zkoušky jako téma MeSH
• komplement C3 analýza   MeSH
• kvalita života MeSH
• lidé MeSH
• systémový lupus erythematodes farmakoterapie   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Lately, mounting evidence has shown that B cells play an important role in the pathogenesis of type 1 diabetes (T1D). Here, we present alterations in B cell subsets including BAFF receptor (BAFFR) expression in cohorts of patients with type 1 diabetes (T1D) and their relatives. PATIENTS AND METHODS: B cells were studied in 438 patients with T1D (158 at disease onset and 280 with long-term disease), 136 first-degree relatives and 53 healthy controls. The B cell panel included transitional, naïve, MZ-like, switched memory B cells and plasmablasts. We also measured serum BAFF levels as well as BAFFR expression on both B and T cells. Moreover, the effect of BAFF on T and B lymphocytes was analysed in vitro. RESULTS: We observed a significant decrease in the proportion of transitional B cells in the patients with T1D, accompanied by an increased proportion of plasmablasts, especially in recent-onset patients and their relatives. While the BAFF serum levels did not differ in the patients with T1D, BAFFR-expressing B and especially T cell numbers were reduced in the T1D cohort, with the exception of patients with recent-onset disease who exhibited a significant increase in the number of BAFFR-expressing T cells. T cell activation and B cell proliferation were more pronounced after activation with BAFF in the T1D cohort compared to controls. CONCLUSION: The B cell panel in patients with T1D is characterized by significantly reduced populations of B cells in their early stages of development with a shift towards plasma cells. The dynamics of BAFFR-expressing B and T cells and the more pronounced responsiveness of the T1D T cells to BAFF point to the role of BAFF and T and B cell cooperation in the development of T1D.

• MeSH
• buněčná diferenciace * MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• faktor aktivující B-buňky metabolismus   MeSH
• kojenec MeSH
• kultivované buňky MeSH
• lidé MeSH
• mezibuněčná komunikace MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• plazmatické buňky imunologie   MeSH
• podskupiny B-lymfocytů imunologie   MeSH
• předškolní dítě MeSH
• receptor faktoru aktivujícího B-buňky genetika   metabolismus   MeSH
• regulace genové exprese MeSH
• T-lymfocyty imunologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Serum protein fingerprints associated with MGUS and MM and their changes in MM after autologous stem cell transplantation (MM-ASCT, day 100) remain unexplored. Using highly-sensitive Proximity Extension ImmunoAssay on 92 cancer biomarkers (Proseek Multiplex, Olink), enhanced serum levels of Adrenomedullin (ADM, Pcorr= .0004), Growth differentiation factor 15 (GDF15, Pcorr= .003), and soluble Major histocompatibility complex class I-related chain A (sMICA, Pcorr= .023), all prosurvival and chemoprotective factors for myeloma cells, were detected in MM comparing to MGUS. Comparison of MGUS and healthy subjects revealed elevation of angiogenic and antia-poptotic midkine (Pcorr= .0007) and downregulation of Transforming growth factor beta 1 (TGFB1, Pcorr= .005) in MGUS. Importantly, altered serum pattern was associated with MM-ASCT compared to paired MM at the diagnosis as well as to healthy controls, namely by upregulated B-Cell Activating Factor (sBAFF) (Pcorr< .006) and sustained elevation of other pro-tumorigenic factors. In conclusion, the serum fingerprints of MM and MM-ASCT were characteristic by elevated levels of prosurvival and chemoprotective factors for myeloma cells.

• MeSH
• adrenomedulin MeSH
• autologní transplantace MeSH
• cytokiny MeSH
• faktor aktivující B-buňky MeSH
• imunoanalýza MeSH
• krevní proteiny analýza   MeSH
• mezibuněčné signální peptidy a proteiny MeSH
• mnohočetný myelom MeSH
• monoklonální gamapatie nejasného významu MeSH
• nádorové biomarkery MeSH
• růstový diferenciační faktor 15 MeSH
• transplantace kmenových buněk MeSH

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disorder of the central nervous system (CNS). Its immunopathogenesis has been proposed to include early cerebrospinal fluid (CSF) lymphocytosis, subsequent CNS disease restriction and B cell mechanism predominance. There are limited data regarding T cell involvement in the disease. To contribute to the current knowledge, we investigated the complex system of chemokines and cytokines related to B and T cell functions in CSF and sera samples from anti-NMDAR encephalitis patients at different time-points of the disease. One patient in our study group had a long-persisting coma and underwent extraordinary immunosuppressive therapy. METHODS: Twenty-seven paired CSF/serum samples were collected from nine patients during the follow-up period (median 12 months, range 1-26 months). The patient samples were stratified into three periods after the onset of the first disease symptom and compared with the controls. Modified Rankin score (mRS) defined the clinical status. The concentrations of the chemokines (C-X-C motif ligand (CXCL)10, CXCL8 and C-C motif ligand 2 (CCL2)) and the cytokines (interferon (IFN)γ, interleukin (IL)4, IL7, IL15, IL17A and tumour necrosis factor (TNF)α) were measured with Luminex multiple bead technology. The B cell-activating factor (BAFF) and CXCL13 concentrations were determined via enzyme-linked immunosorbent assay. We correlated the disease period with the mRS, pleocytosis and the levels of all of the investigated chemokines and cytokines. Non-parametric tests were used, a P value <0.05 was considered to be significant. RESULTS: The increased CXCL10 and CXCL13 CSF levels accompanied early-stage disease progression and pleocytosis. The CSF CXCL10 and CXCL13 levels were the highest in the most complicated patient. The CSF BAFF levels remained unchanged through the periods. In contrast, the CSF levels of T cell-related cytokines (INFγ, TNFα and IL17A) and IL15 were slightly increased at all of the periods examined. No dynamic changes in chemokine and cytokine levels were observed in the peripheral blood. CONCLUSIONS: Our data support the hypothesis that anti-NMDAR encephalitis is restricted to the CNS and that chemoattraction of immune cells dominates at its early stage. Furthermore, our findings raise the question of whether T cells are involved in this disease.

• MeSH
• B-lymfocyty metabolismus   MeSH
• chemokin CXCL10 MeSH
• chemokin CXCL13 MeSH
• chemokiny MeSH
• cytokiny MeSH
• dítě MeSH
• dospělí MeSH
• encefalitida s protilátkami proti NMDA receptorům terapie   MeSH
• faktor aktivující B-buňky MeSH
• imunoterapie MeSH
• kóma etiologie   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• progrese nemoci MeSH
• steroidy terapeutické užití   MeSH
• T-lymfocyty metabolismus   MeSH
• výměna plazmy MeSH
• výsledek terapie MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The aim of this study was to evaluate serum levels of visfatin in anti-Jo-1-positive myositis patients, its expression in muscle tissue and to investigate potential relationships between visfatin, B-cell activating factor of the TNF family (BAFF), disease activity and anti-Jo-1 autoantibody levels. METHODS: Serum levels of visfatin and BAFF were measured in 38 anti-Jo-1 positive myositis patients and 35 healthy subjects. Disease activity was evaluated by myositis disease activity assessment tool (MYOACT) using visual analogue scales (VAS) and by serum muscle enzymes. Visfatin expression was evaluated by immunohistochemistry in muscle tissue of myositis patients (n=10) and compared with non-inflammatory control muscle tissue samples from patients with myasthenia gravis (n=5). RESULTS: Serum visfatin and BAFF levels were significantly higher in myositis patients compared to healthy subjects and were associated with clinical muscle activity assessed by VAS. Only serum BAFF levels, but not visfatin levels, positively correlated with muscle enzyme concentrations and anti-Jo1 antibody levels. There was a positive correlation between visfatin and BAFF serum levels in myositis patients but a negative correlation was observed in healthy subjects. Visfatin expression was up-regulated in endomysial and perimysial inflammatory infiltrates of muscle tissue from myositis patients. CONCLUSIONS: Up-regulation of visfatin in myositis muscle tissue and an association between increased visfatin levels and muscle disease activity evaluated by MYOACT in anti-Jo-1 positive myositis patients could support possible role of visfatin in the pathogenesis of myositis.

• MeSH
• antinukleární protilátky krev   MeSH
• cytokiny analýza   krev   fyziologie   MeSH
• dospělí MeSH
• faktor aktivující B-buňky analýza   MeSH
• kosterní svaly chemie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myozitida etiologie   imunologie   metabolismus   MeSH
• nikotinamidfosforibosyltransferasa analýza   krev   fyziologie   MeSH
• senioři MeSH
• vizuální analogová stupnice 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

The B-cell activating factor (BAFF) cytokine has important functions for the survival and maturation of B lymphocytes, which implies that this cytokine might play a role in the development of antibody-mediated rejection (AMR) after kidney transplantation. In our study, we compared the concentrations of the soluble BAFF cytokine in kidney graft recipients with AMR and patients without rejection with the goal of testing the hypothesis whether BAFF level measurement might be useful as a diagnostic marker of AMR. The study included a cohort of 19 high-risk patients with diagnosed AMR and 17 control patients free of rejection. BAFF was measured in all patients before transplantation, during the rejection episodes, and three months after transplantation in patients free of rejection using the Luminex technique. Before transplantation, the serum concentrations of BAFF in patients with AMR and kidney recipients without rejection did not significantly differ. After transplantation, however, BAFF levels were significantly lower in patients with AMR and also in patients with concurrent humoral and cellular rejection compared with patients without rejection (p < 0.05 and p < 0.01, respectively). No correlation was found between BAFF and the production of donor-specific antibodies (DSA) before and after transplantation. Patients experiencing AMR and simultaneous cellular and AMR had significantly lower concentrations of BAFF in comparison with patients free of rejection.

• MeSH
• B-lymfocyty imunologie   MeSH
• časové faktory MeSH
• dárci tkání MeSH
• dospělí MeSH
• faktor aktivující B-buňky krev   MeSH
• HLA antigeny chemie   MeSH
• isoprotilátky krev   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• rejekce štěpu krev   imunologie   MeSH
• renální insuficience imunologie   chirurgie   MeSH
• riziko MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• transplantace ledvin * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH