INTRODUCTION/AIMS: Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. METHODS: Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). RESULTS: The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. DISCUSSION: Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

• MeSH
• autoprotilátky krev   MeSH
• činnosti denního života MeSH
• dospělí MeSH
• dvojitá slepá metoda MeSH
• imunologické faktory terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• intravenózní imunoglobuliny * terapeutické užití   škodlivé účinky   aplikace a dávkování   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myasthenia gravis * farmakoterapie   MeSH
• prospektivní studie MeSH
• receptory cholinergní * imunologie   MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze II MeSH
• multicentrická studie MeSH
• randomizované kontrolované studie MeSH

SIGNIFICANCE STATEMENT: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. More than 1500 patients were collated in an international longitudinal study to revise the ANCA kidney risk score. The score showed satisfactory performance, mimicking the original study (Harrell's C=0.779). In the development cohort of 959 patients, no additional parameters aiding the tool were detected, but replacing the GFR with creatinine identified an additional cutoff. The parameter interstitial fibrosis and tubular atrophy was modified to allow wider access, risk points were reweighted, and a fourth risk group was created, improving predictive ability (C=0.831). In the validation, the new model performed similarly well with excellent calibration and discrimination ( n =480, C=0.821). The revised score optimizes prognostication for clinical practice and trials. BACKGROUND: Reliable prediction tools are needed to personalize treatment in ANCA-associated GN. A retrospective international longitudinal cohort was collated to revise the ANCA renal risk score. METHODS: The primary end point was ESKD with patients censored at last follow-up. Cox proportional hazards were used to reweight risk factors. Kaplan-Meier curves, Harrell's C statistic, receiver operating characteristics, and calibration plots were used to assess model performance. RESULTS: Of 1591 patients, 1439 were included in the final analyses, 2:1 randomly allocated per center to development and validation cohorts (52% male, median age 64 years). In the development cohort ( n =959), the ANCA renal risk score was validated and calibrated, and parameters were reinvestigated modifying interstitial fibrosis and tubular atrophy allowing semiquantitative reporting. An additional cutoff for kidney function (K) was identified, and serum creatinine replaced GFR (K0: <250 μ mol/L=0, K1: 250-450 μ mol/L=4, K2: >450 μ mol/L=11 points). The risk points for the percentage of normal glomeruli (N) and interstitial fibrosis and tubular atrophy (T) were reweighted (N0: >25%=0, N1: 10%-25%=4, N2: <10%=7, T0: none/mild or <25%=0, T1: ≥ mild-moderate or ≥25%=3 points), and four risk groups created: low (0-4 points), moderate (5-11), high (12-18), and very high (21). Discrimination was C=0.831, and the 3-year kidney survival was 96%, 79%, 54%, and 19%, respectively. The revised score performed similarly well in the validation cohort with excellent calibration and discrimination ( n =480, C=0.821). CONCLUSIONS: The updated score optimizes clinicopathologic prognostication for clinical practice and trials.

• MeSH
• ANCA-asociované vaskulitidy * diagnóza   MeSH
• atrofie MeSH
• fibróza MeSH
• kreatinin MeSH
• ledviny MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• protilátky proti cytoplazmě neutrofilů * MeSH
• retrospektivní studie MeSH
• rizikové faktory MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

OBJECTIVES: In aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), disability accrual is mostly attributed to relapses. This study aimed to assess the prevalence of progression independent of relapse activity (PIRA) and relapse-associated worsening (RAW) in AQP4-IgG NMOSD. METHODS: This was a retrospective cohort study of patients with AQP4-IgG NMOSD enrolled in the MSBase international data registry. Patients required a minimum of 3 recorded Expanded Disability Status Scale (EDSS) scores: baseline, event, and a 6-month confirmation score. Presence and absence of relapses between the baseline and event EDSS scores determined RAW and PIRA, respectively. Descriptive statistics were used to present the results. RESULTS: A total of 181 patients followed for a median of 4.5 years (Q1 1.7, Q3 7.8) were included. Most patients were female (88.4%), and the median age at disease onset was 38.1 years. Overall, 4 patients (2.2%) developed 5 incidences of PIRA and 13 patients developed RAW (7.2%). DISCUSSION: This multicenter study highlights that PIRA is very rare in AQP4-IgG NMOSD. Limitations of this study include the sole focus of overall EDSS to measure disability, lack of requirement for a second EDSS score to confirm baseline EDSS, and the absence of magnetic resonance imaging information for all patients.

• MeSH
• akvaporin 4 * imunologie   MeSH
• autoprotilátky * krev   MeSH
• dospělí MeSH
• imunoglobulin G * krev   MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• neuromyelitis optica * imunologie   epidemiologie   MeSH
• posuzování pracovní neschopnosti MeSH
• prevalence MeSH
• progrese nemoci * MeSH
• recidiva * MeSH
• retrospektivní studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

BACKGROUND: The presence of ACPA significantly increases the risk of developing RA. Dysregulation of lymphocyte subpopulations was previously described in RA. Our objective was to propose the predictive model for progression to clinical arthritis based on peripheral lymphocyte subsets and ACPA in individuals who are at risk of RA. METHODS: Our study included 207 at-risk individuals defined by the presence of arthralgias and either additional ACPA positivity or meeting the EULAR definition for clinically suspect arthralgia. For the construction of predictive models, 153 individuals with symptom duration ≥12 months who have not yet progressed to arthritis were included. The lymphocyte subsets were evaluated using flow cytometry and anti-CCP using ELISA. RESULTS: Out of all individuals with arthralgia, 41 progressed to arthritis. A logistic regression model with baseline peripheral blood lymphocyte subpopulations and ACPA as predictors was constructed. The resulting predictive model showed that high anti-CCP IgG, higher percentage of CD4+ T cells, and lower percentage of T and NK cells increased the probability of arthritis development. Moreover, the proposed classification decision tree showed that individuals having both high anti-CCP IgG and low NK cells have the highest risk of developing arthritis. CONCLUSIONS: We propose a predictive model based on baseline levels of lymphocyte subpopulations and ACPA to identify individuals with arthralgia with the highest risk of progression to clinical arthritis. The final model includes T cells and NK cells, which are involved in the pathogenesis of RA. This preliminary model requires further validation in larger at-risk cohorts.

• MeSH
• artralgie * imunologie   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• podskupiny lymfocytů * imunologie   MeSH
• prediktivní hodnota testů MeSH
• progrese nemoci * MeSH
• protilátky proti citrulinovaným peptidům * krev   imunologie   MeSH
• revmatoidní artritida * imunologie   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: We recently described magnetic resonance imaging (MRI) features of children with transverse myelitis (TM) at first event with important and unique differences depending on the underlying disease entity. OBJECTIVE: To study the resolution of lesions over time in children with TM due to MOG-antibody associated disorders (MOGAD), multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) or double seronegative TM. PATIENTS AND METHODS: In this prospective study, 78 children from 29 different medical centres with TM as part of MOGAD (n = 34), MS (n = 20), NMOSD (n = 5) and in double seronegative children (n = 19) were included. A grading system consisting of 4 grades (grade 0 = complete resolution; grade 3 = no resolution at all) was used to compare the degree of lesion resolution over time in the different disease entities. Time to lesion resolution was evaluated by Kaplan-Meier statistics and log-rank test. RESULTS: Significant differences of the interval between first MRI until resolution of lesions were observed between the four disease entities. The most rapid and complete resolution was seen in MOGAD, followed by double seronegative, MS and NMOSD. Median periods until total resolution (grade 0) were 191 days (MOGAD), 750 days (double seronegative), 1117 days (MS), while none of the patients with NMOSD reached a complete resolution during the observation period. The better prognosis of MOGAD compared to MS was independent of sex, age, oligoclonal bands and cell count in the multivariate Cox analysis (P < 0.001). CONCLUSION: Children with TM and antibodies to MOG show a faster resolution of radiological lesions compared to children with MS and NMOSD.

• MeSH
• autoprotilátky krev   MeSH
• dítě MeSH
• glykoprotein v myelinu oligodendrocytů imunologie   MeSH
• lidé MeSH
• magnetická rezonanční tomografie * MeSH
• mícha diagnostické zobrazování   patologie   MeSH
• mladiství MeSH
• následné studie MeSH
• neuromyelitis optica * diagnostické zobrazování   MeSH
• předškolní dítě MeSH
• prospektivní studie MeSH
• roztroušená skleróza * diagnostické zobrazování   patologie   MeSH
• transverzální myelitida * diagnostické zobrazování   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH

Autoimunní revmatická onemocnění jsou rozmanitou skupinou stavů, které se mohou projevovat tvorbou autoprotilátek, funkčními poruchami imunity a systémovými projevy. Diagnostika může být obtížná kvůli mnoha nespecifickým projevům. Klíčovým testem, který v praxi využíváme, je stanovení orgánově nespecifických autoprotilátek. Autoprotilátky vyskytující se u osob se systémovými revmatickými chorobami mohou sloužit nejen jako markery pro klasifikaci, diagnózu a prognózu onemocnění, ale také při hodnocení aktivity onemocnění a při rozhodování o léčebném postupu. Autoprotilátky také často hrají přímou úlohu v patogenezi jednotlivých onemocnění.

Autoimmune rheumatic diseases represent a diverse group of conditions that may manifest with the production of autoantibodies, immune dysfunction, and systemic symptoms. Diagnosis can be challenging due to many nonspecific manifestations. A key test used in practice is the detection of organ-nonspecific autoantibodies. Autoantibodies present in individuals with systemic rheumatic diseases can serve not only as markers for classification, diagnosis, and prognosis but also in assessing disease activity and guiding treatment decisions. Autoantibodies often also play a direct role in the pathogenesis of individual diseases.

• MeSH
• antigeny jaderné imunologie   MeSH
• antinukleární protilátky imunologie   MeSH
• autoimunitní nemoci diagnóza   imunologie   MeSH
• autoprotilátky * imunologie   klasifikace   MeSH
• imunologické techniky metody   MeSH
• lidé MeSH
• myozitida imunologie   MeSH
• protilátky proti cytoplazmě neutrofilů imunologie   MeSH
• protilátky imunologie   klasifikace   MeSH
• revmatické nemoci * diagnóza   imunologie   MeSH
• revmatoidní faktor imunologie   MeSH
• systémová sklerodermie imunologie   MeSH
• systémový lupus erythematodes diagnóza   imunologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

Tick-borne encephalitis (TBE) virus (TBEV) is transmitted to humans via tick bites. Infection is benign in >90% of the cases but can cause mild (<5%), moderate (<4%), or severe (<1%) encephalitis. We show here that ∼10% of patients hospitalized for severe TBE in cohorts from Austria, Czech Republic, and France carry auto-Abs neutralizing IFN-α2, -β, and/or -ω at the onset of disease, contrasting with only ∼1% of patients with moderate and mild TBE. These auto-Abs were found in two of eight patients who died and none of 13 with silent infection. The odds ratios (OR) for severe TBE in individuals with these auto-Abs relative to those without them in the general population were 4.9 (95% CI: 1.5-15.9, P < 0.0001) for the neutralization of only 100 pg/ml IFN-α2 and/or -ω, and 20.8 (95% CI: 4.5-97.4, P < 0.0001) for the neutralization of 10 ng/ml IFN-α2 and -ω. Auto-Abs neutralizing type I IFNs accounted for ∼10% of severe TBE cases in these three European cohorts.

• MeSH
• autoprotilátky * imunologie   MeSH
• dospělí MeSH
• interferon typ I * imunologie   MeSH
• klíšťová encefalitida * imunologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutralizující protilátky * imunologie   MeSH
• senioři MeSH
• viry klíšťové encefalitidy 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
• Geografické názvy
• Česká republika MeSH
• Rakousko MeSH

• MeSH
• autoprotilátky MeSH
• lidé MeSH
• rizikové faktory MeSH
• systémová sklerodermie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Myositidy neboli idiopatické zánětlivé myopatie tvoří heterogenní skupinu autoimunitních onemocnění příčně pruhovaných svalů. Jejich diagnostika není jednoduchá, protože často dochází k překryvu s dalšími autoimunitními onemocněními. Navíc není konsensus na klasifikaci myositid. Mezi podtypy myositidy patří polymyositida, dermatomyositida, myositida s inkluzivními tělísky, antisyntetázový syndrom a další. Z vyšetření je důležité provedení biopsie svalu, dále biochemické stanovení hladin svalových enzymů v séru pacienta a v současné době také vyšetření autoprotilátek – jak specifických pro myositidy, tak s myositidami asociovaných – které je užitečné pro určení podtypu myositidy. Myositidy jsou často dobře léčitelné, především kortikoidy, a proto je odlišení od jiných svalových onemocnění a jejich správná diagnóza stěžejní pro úspěšnou léčbu.

Myositis, also known as idiopathic inflammatory myopathies, is a heterogeneous group of autoimmune diseases affecting skeletal muscles. The diagnosis is not easy, because myositis itself often co-occur with other autoimmune conditions. Moreover, there is no consensus on myositis classification. Myositis subtypes include polymyositis, dermatomyositis, inclusion body myositis, anti-synthetase syndrome, and others. From a diagnostic standpoint, muscle biopsy is important, along with biochemical determination of muscle enzyme levels in the patient‘s serum. Cu- rrently, the examination of autoantibodies – both specific to myositis and associated with myositis – is also useful when determining the myositis subtype. Myositis is often highly treatable, mainly with corticosteroids, and for that reason distinguishing myositis from other muscle disorders and making an accurate diagnosis is essential for successful treatment.

• MeSH
• autoimunitní nemoci MeSH
• autoprotilátky MeSH
• biopsie MeSH
• kreatinkinasa MeSH
• lidé MeSH
• myozitida * diagnóza   farmakoterapie   klasifikace   MeSH
• sérologické testy * metody   MeSH
• svaly enzymologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

OBJECTIVE: To study the trajectories of changes in damage over time and explore associations with autoantibody defined subgroups using a large international cohort of patients with idiopathic inflammatory myopathies (IIM). METHODS: Data from the MYONET registry, including patients who were tested for autoantibodies and had at least one assessment of damage using the Myositis Damage Index (MDI), were analyzed. Patients were sub-grouped according to their autoantibody profiles (myositis-specific, myositis-associated, or seronegative). The index date was defined as the time point for the first registered MDI assessment. The longitudinal trajectories of damage with autoantibody status as the main predictor were analyzed using linear mixed models. RESULTS: A total of 757 adult patients were included in this study. Each year of disease duration since diagnosis had an estimated MDI score increase of 0.16 units for the seronegative group (reference). Compared with the seronegative group as reference, patients with dermatomyositis-specific autoantibodies developed less damage per year of follow-up since diagnosis (average 0.08 less score, P = 0.04), whereas patients with anti-PM/Scl autoantibodies developed more damage per year of follow-up since diagnosis (average 0.28 higher score, P = 0.03) independent of sex and age at diagnosis. The seronegative subgroup and the immune-mediated necrotizing myopathy autoantibody subgroup had the strongest correlation between severity of muscle damage and HAQ-DI scores at five years of follow-up, rho=0.84, P < 0.001 and rho=0.72, P < 0.001, respectively. CONCLUSION: Our study is the first to describe patterns and trajectories of change in damage over time in relation to autoantibody defined subgroups in a large international multicenter cohort of patients with IIM. Patients with anti-PM/Scl scored a greater extent of damage, whereas patients with dermatomyositis-specific antibodies had less damage than seronegative patients. Severity in muscle damage had moderate to strong correlation with functional disability among the IMNM and seronegative subgroups with lower correlations for the other subgroups. These findings suggest that autoantibodies may be useful predictors of long-term damage.

• MeSH
• autoprotilátky * krev   imunologie   MeSH
• dermatomyozitida imunologie   krev   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• myozitida * imunologie   krev   MeSH
• progrese nemoci MeSH
• registrace * MeSH
• senioři MeSH
• stupeň závažnosti nemoci MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH