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
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) can be categorised into aquaporin-4 antibody (AQP4-IgG) NMOSD or seronegative NMOSD. While our knowledge of AQP4-IgG NMOSD has evolved significantly in the past decade, seronegative NMOSD remains less understood. This study aimed to evaluate the predictors of relapses and treatment responses in AQP4-IgG NMOSD and seronegative NMOSD. METHODS: This was a multicentre, international, retrospective cohort study using the MSBase registry. Recurrent relapse risk was assessed using an Andersen-Gill model and risk of first relapse was evaluated using a Cox proportional hazards model. Covariates that putatively influence relapse risk included demographic factors, clinical characteristics and immunosuppressive therapies; the latter was assessed as a time-varying covariate. RESULTS: A total of 398 patients (246 AQP4-IgG NMOSD and 152 seronegative NMOSD) were included. The AQP4-IgG NMOSD and seronegative NMOSD patients did not significantly differ by age at disease onset, ethnicity or annualised relapse rate. Both low-efficacy and high-efficacy immunosuppressive therapies were associated with significant reductions in recurrent relapse risk, with notably greater protection conferred by high-efficacy therapies in both AQP4-IgG NMOSD (HR 0.27, 95% CI 0.15 to 0.49, p<0.001) and seronegative NMOSD (HR 0.21, 95% CI 0.08 to 0.51, p<0.001). Longer disease duration (HR 0.97, 95% CI 0.95 to 0.99, p<0.001) and male sex (HR 0.52, 95% CI 0.34 to 0.84, p=0.007) were additional protective variables in reducing the recurrent relapse risk for the AQP4-IgG NMOSD group. CONCLUSION: Although further studies are needed to improve our understanding of seronegative NMOSD, our findings underscore the importance of aggressive treatment with high-efficacy immunotherapies in both NMOSD subtypes, regardless of serostatus.
- MeSH
- akvaporin 4 * imunologie MeSH
- autoprotilátky krev MeSH
- dospělí MeSH
- imunoglobulin G * krev MeSH
- imunosupresiva terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- neuromyelitis optica * imunologie farmakoterapie MeSH
- recidiva * MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- výsledek terapie 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
Tranzientní hypogamaglobulinemie je poměrně častá primární protilátková imunodeficience kojenců a batolat se širokým klinickým obrazem. Patofyziologickým podkladem je opožděný nástup tvorby vlastních imunoglobulinů, rezultující v přechodný pokles sérové koncentrace IgG u kojence. THI většinou spontánně odezní ve věku 2 až 6 let. V laboratoři dominuje snížená sérová koncentrace IgG (ev. i IgA a IgM) při normálním zastoupení B-lymfocytů. V diferenciální diagnostice zvažujeme i jiné imunodeficience. Velmi důležitá je mezioborová spolupráce.
Transient hypogammaglobulinemia is a relatively common primary antibody immunodeficiency in infants and toddlers with a wide clinical picture. The pathophysiological basis is a delayed onset of the production of own immunoglobulins, resulting in a temporary decrease in serum IgG concentration in the infant. THI usually resolves spontaneously between the ages of 2 and 6 years. In the laboratory, a reduced serum IgG concentration (possibly also IgA and IgM) dominates with a normal representation of B-lymphocytes. In the differential diagnosis, we also consider other immunodeficiencies. Interdisciplinary cooperation is very important.
- Klíčová slova
- THI, etiopathogenesis, clinical evaluation, differential diagnosis, treatment, THI, etiopatogeneze, klinické hodnocení, diferenciální diagnostika, léčba,
- MeSH
- alergie etiologie imunologie MeSH
- antibakteriální látky terapeutické užití MeSH
- běžná variabilní imunodeficience * diagnóza epidemiologie terapie MeSH
- dermatitida etiologie imunologie MeSH
- diferenciální diagnóza MeSH
- dítě * MeSH
- imunologické testy MeSH
- infekce dýchací soustavy etiologie imunologie MeSH
- intravenózní imunoglobuliny terapeutické užití MeSH
- lidé MeSH
- Check Tag
- dítě * MeSH
- lidé MeSH
Tick-borne encephalitis virus (TBEV) infection can manifest as disease of variable severity, ranging from subclinical infection to severe disease with neurological involvement and potentially fatal outcome. Although TBE is recognized as a major public health problem in Europe, the true burden of disease is potentially underestimated. Here, we investigated TBEV-specific antibody prevalence, infection incidence, and seroreversion and antibody decline rates in a prospective Swiss healthcare worker (HCW) cohort. We screened serum samples from 1444 HCWs between June and October 2020, and from a subset again between August and September 2021, using a TBEV envelope (E) protein IgG ELISA. Positive samples underwent further analysis with a TBEV non-structural protein 1 (NS1) IgG ELISA, and seroconversions in unvaccinated individuals were confirmed by seroneutralization testing. Questionnaire data were used to determine vaccination status and risk factors. TBEV E protein-specific IgG prevalence was 72.1% (95% CI 68.2-75.7%) in TBEV-vaccinated and 6% (95% CI 4.4-7.8%) in unvaccinated individuals. The estimated annual incidence of infection was 735/100,000. Age was the only factor significantly associated with seroprevalence. The seroreversion rate in unvaccinated individuals was 30.3% within one year, which is almost ten times higher than in vaccinated individuals (3.4%, annual decline rate 8.0%). NS1-specific IgG antibodies were six times more common in vaccinated than unvaccinated HCWs. In conclusion, undetected TBEV infections are common, and infection incidence is much higher than reported clinical cases. Individuals with abortive infections have high antibody decline and seroreversion rates. Whether lifelong protection is conferred and by which immune subsets remain unclear.
- MeSH
- dospělí MeSH
- imunoglobulin G krev MeSH
- incidence MeSH
- klíšťová encefalitida * epidemiologie imunologie krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- protilátky virové * krev MeSH
- senioři MeSH
- séroepidemiologické studie MeSH
- viry klíšťové encefalitidy * imunologie MeSH
- zdravotnický personál statistika a číselné údaje 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
- Švýcarsko MeSH
Toxocara canis is a widespread parasite of canids with a wide range of paratenic hosts, but also one of the overlooked agents causing nervous system infections of humans. Previous experimental infections of mice demonstrated the impact of high infection doses of larvae on neurobehavioral disorders and pathological changes. In contrast to previous studies, we aimed to investigate the long-term (up to 100 weeks) impact of low- to high-dose infection in mice. We focused on their physical condition, motor skills, and the accompanying pathologies in the brain. Three groups of BALB/c mice were infected with 10, 100, and 1000 T. canis larvae/mouse and specific anti-T. canis excretory-secretory antigens immunoglobulin G antibody response, general condition, and motor skills were tested in defined intervals within 100 weeks after infection. The number of larvae in selected organs was assessed and the pathological changes in the brain were studied histologically. As a result, subtle to severe impairments in general condition and motor skills were detected, with generally earlier onsets occurring the higher the infection dose was. The specific immunoglobulin G antibody levels corresponding to the infection dose were detected in all infected groups. Necrosis, cellular infiltrations, and foamy cells developed in moderate- and high-infection dose mice, in contrast with hemorrhages detected in all groups. This study demonstrated the long-term negative impact of T. canis infection on the paratenic host, particularly at moderate and high infectious doses. Although pathological changes in the brain were observed even in low-infection dose mice, their physical and motor condition was comparable to the control group.
- MeSH
- imunoglobulin G * krev MeSH
- larva MeSH
- modely nemocí na zvířatech MeSH
- mozek * parazitologie patologie MeSH
- myši inbrední BALB C * MeSH
- myši MeSH
- protilátky helmintové * krev MeSH
- Toxocara canis * imunologie MeSH
- toxokaróza * parazitologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Highly sensitized (HS) patients in need of kidney transplantation (KTx) typically spend a longer time waiting for compatible kidneys, are unlikely to receive an organ offer, and are at increased risk of antibody-mediated rejection (AMR). Desensitization using imlifidase, which is more rapid and removes total body immunoglobulin G (IgG) to a greater extent than other methods, enables transplantation to occur between HLA-incompatible (HLAi) donor-recipient pairs and allows patients to have greater access to KTx. However, when the project was launched there was limited data and clinical experience with desensitization in general and with imlifidase specifically. Hence, this Delphi methodology was used to reach a consensus from a multi-disciplinary team (MDT) of experts from 15 countries on the management of HS patients undergoing imlifidase HLAi from a deceased donor (DD) KTx. This Delphi consensus provides clinical practice guidance on the use of imlifidase in the end-to-end management of HS patients undergoing an HLAi DD KTx and supports centers in the development of guidelines for the utilization and integration of imlifidase into clinical practice.
- MeSH
- dárci tkání * MeSH
- delfská metoda * MeSH
- desenzibilizace imunologická * metody MeSH
- HLA antigeny * imunologie MeSH
- imunoglobulin G MeSH
- konsensus * MeSH
- lidé MeSH
- rejekce štěpu prevence a kontrola imunologie MeSH
- transplantace ledvin * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: Lyme borreliosis (LB), an infection caused by Borrelia burgdorferi sensu lato (Bbsl), is the most common tick-borne disease in Europe. To further characterize the LB burden in the Czech Republic, we conducted a seroprevalence study and estimated the incidence of symptomatic Bbsl infections. METHODS: Anti-Bbsl IgM and IgG antibodies were detected in sera collected from the adult population in 2011 -2012 by enzyme-linked immunosorbent assay and immunoblot tests at the National Reference Laboratory. The incidence of symptomatic Bbsl infections was estimated from the seroprevalence results and the symptomatic proportion and duration of persistence of anti-Bbsl IgG antibodies in Bbsl-infected individuals. Surveillance under-detection of symptomatic Bbsl infections was estimated by comparing surveillance-reported and seroprevalence-based incidence. RESULTS: Samples from 1996 adults were tested; the median age (range) was 45 (18 -87) years; 1037 (52.0 %) were female. The prevalence (with 95 % confidence interval) of anti-Bbsl IgG, and IgM and/or IgG (IgM/IgG) antibodies was 6.3 % (5.3 -7.5 %), and 9.5 % (8.3 -10.9 %), respectively. The IgM/IgG prevalence was 7.8 % (6.5 -9.2 %) in Bohemia and 15.3 % (12.2 -19.0 %) in Moravia. There were an estimated 30,563 (26,550 -34,962) symptomatic incident Bbsl infections in adults in the Czech Republic in 2012, for an incidence of 352.2 (306.0 -402.9) symptomatic Bbsl infections per 100,000 adults per year. There were an estimated 11 (10 -13) symptomatic Bbsl infections for each surveillance-reported LB case in the Czech Republic in 2012. CONCLUSIONS: There is high incidence of symptomatic Bbsl infections in the Czech Republic, particularly in Moravia. Interventions are needed to address the substantial burden of LB in the Czech Republic.
- MeSH
- Borrelia burgdorferi komplex * imunologie izolace a purifikace MeSH
- dospělí MeSH
- ELISA * MeSH
- imunoglobulin G * krev MeSH
- imunoglobulin M * krev MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymeská nemoc * epidemiologie mikrobiologie krev MeSH
- mladiství MeSH
- mladý dospělý MeSH
- prevalence MeSH
- protilátky bakteriální * krev MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- séroepidemiologické studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with significant cardiovascular complications, including myocardial infection and pulmonary embolism. This study aims to elucidate the relationship between the presence of SARS-CoV-2 RNA in the myocardium of the left ventricle and the levels of IgG and IgM antibodies against the SARS-CoV-2 virus in deceased COVID-19 patients. We conducted a post-mortem examination on 91 individuals who succumbed to COVID-19-related complications. The presence of SARS-CoV-2 RNA in the myocardium of the left ventricle was analyzed reverse transcription real time PCR (RT-qPCR) (EliGene® COVID19 UKV/SAV RT kit, Elisabeth Pharmacon), and antibody levels in serum were analyzed by serological assays (VIDAS SARS-COV-2 IgM and VIDAS SARS-COV-2 IgG II tests, BioMérieux). Of the heart tissue samples, 44 % tested positive for SARS-CoV-2 RNA. Our findings indicate that any detectable level of IgG antibodies against SARS-CoV-2 reduces the risk of viral penetration into the myocardium by more than fourfold. Specifically, individuals with detectable levels of IgG and IgM antibodies exhibited a significantly reduced presence of SARS-CoV-2 RNA in cardiac tissues (p<0.0001 for IgG and p<0.001 for IgM). Notably, all patients who died from pulmonary embolism had elevated levels of IgG antibodies. The study underscores the protective role of IgG and IgM antibodies in preventing SARS-CoV-2 penetration into cardiac tissues. However, high antibody titers were associated with fatal outcomes such as pulmonary embolism, pointing to the intricate balance of immune response in COVID-19 pathology. Key words SARS-CoV-2, Antibody, IgG, IgM, Cardiac damage, qPCR, Pneumonia, Pulmonary embolism, Heart failure.
- MeSH
- COVID-19 * imunologie virologie MeSH
- dospělí MeSH
- imunoglobulin G * krev MeSH
- imunoglobulin M * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard * imunologie metabolismus MeSH
- protilátky virové * krev MeSH
- RNA virová krev MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři nad 80 let MeSH
- senioři 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
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
