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
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
V souboru očkovaných a neočkovaných jedinců, kteří prodělali nebo neprodělali onemocnění Covid-19, jsme sledovali vztah mezi anti-SARS-CoV-2 IgG a některými parametry, které mají dle literatury význam při rozvoji a průběhu onemocnění Covid-19. Šlo o celkové IgG, podtřídy IgG1-4, složky komplementu C3c, C4 a cirkulující imunokomplexy (CIK). Zjistili jsme, že neočkovaní, očkovaní vakcínou Pfizer/BioNTech a Moderna a rovněž prodělavší a neprodělavší onemocnění Covid-19 se významně liší v hladině antiSARS-CoV-2 IgG. Očkování mělo na výši hladiny protilátek větší vliv než prodělání onemocnění. IgG4 se zvýšilo u očkovaných po vakcíně Pfizer/BioNTech. Ostatní podtřídy IgG, celkové IgG, CIK a složky komplementu se mezi skupinami statisticky významně nelišily.
In a group of vaccinated and unvaccinated individuals who did or did not experience Covid-19 disease, we monitored the relationship between anti-SARS-CoV-2 IgG and some parameters that, according to the literature, are important in the development and course of illness of Covid-19. These were total IgG, IgG1-4 subclasses, complement components C3c, C4 and circulating immune complexes (CIC). We found that unvaccinated, vaccinated with Pfizer/BioNTech and Moderna vaccine, as well as advanced and non-advanced Covid-19 patients differed significantly in the level of anti-SARS-CoV-2 IgG. Vaccination had a greater effect on the level of antibodies than experiencing the disease. IgG4 increased in vaccinees after the Pfizer/BioNTech vaccine. Other IgG subclasses, total IgG, CIC and complement components were not statistically significantly different between groups.
- MeSH
- COVID-19 * imunologie prevence a kontrola MeSH
- dospělí MeSH
- ELISA přístrojové vybavení MeSH
- imunoglobulin G analýza imunologie účinky léků MeSH
- imunokomplex MeSH
- indikátory a reagencie klasifikace MeSH
- komplement MeSH
- lidé středního věku MeSH
- lidé MeSH
- nefelometrie a turbidimetrie přístrojové vybavení MeSH
- vakcinace * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- klinická studie MeSH
- práce podpořená grantem MeSH
In intravenous immunoglobulins (IVIG), and some other immunoglobulin products, protein particles have been implicated in adverse events. Role and mechanisms of immunoglobulin particles in vascular adverse effects of blood components and manufactured biologics have not been elucidated. We have developed a model of spherical silica microparticles (SiMPs) of distinct sizes 200-2000 nm coated with different IVIG- or albumin (HSA)-coronas and investigated their effects on cultured human umbilical vein endothelial cells (HUVEC). IVIG products (1-20 mg/mL), bare SiMPs or SiMPs with IVIG-corona, did not display significant toxicity to unstimulated HUVEC. In contrast, in TNFα-stimulated HUVEC, IVIG-SiMPs induced decrease of HUVEC viability compared to HSA-SiMPs, while no toxicity of soluble IVIG was observed. 200 nm IVIG-SiMPs after 24 h treatment further increased ICAM1 (intercellular adhesion molecule 1) and tissue factor surface expression, apoptosis, mammalian target of rapamacin (mTOR)-dependent activation of autophagy, and release of extracellular vesicles, positive for mitophagy markers. Toxic effects of IVIG-SiMPs were most prominent for 200 nm SiMPs and decreased with larger SiMP size. Using blocking antibodies, toxicity of IVIG-SiMPs was found dependent on FcγRII receptor expression on HUVEC, which increased after TNFα-stimulation. Similar results were observed with different IVIG products and research grade IgG preparations. In conclusion, submicron particles with immunoglobulin corona induced size-dependent toxicity in TNFα-stimulated HUVEC via FcγRII receptors, associated with apoptosis and mTOR-dependent activation of autophagy. Testing of IVIG toxicity in endothelial cells prestimulated with proinflammatory cytokines is relevant to clinical conditions. Our results warrant further studies on endothelial toxicity of sub-visible immunoglobulin particles.
- MeSH
- apoptóza účinky léků MeSH
- autofagie * účinky léků MeSH
- endoteliální buňky pupečníkové žíly (lidské) * účinky léků metabolismus MeSH
- intravenózní imunoglobuliny * MeSH
- lidé MeSH
- mezibuněčná adhezivní molekula-1 metabolismus MeSH
- oxid křemičitý chemie toxicita MeSH
- proteinová korona metabolismus MeSH
- receptory IgG * metabolismus MeSH
- TNF-alfa * metabolismus MeSH
- TOR serin-threoninkinasy metabolismus MeSH
- velikost částic MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a peripheral nerve disorder characterised by weakness and sensory loss. We assessed the neonatal Fc receptor inhibitor rozanolixizumab for CIDP management. METHODS: CIDP01 (NCT03861481) was a randomised, subject-blind, investigator-blind, placebo-controlled, phase 2a study. Adults with definite or probable CIDP receiving subcutaneous or intravenous immunoglobulin maintenance therapy were randomised 1:1 to 12 once-weekly subcutaneous infusions of rozanolixizumab 10 mg/kg or placebo, stratified according to previous immunoglobulin administration route. Investigators administering treatment and assessing efficacy, and patients, were blinded. The primary outcome was a change from baseline (CFB) to day 85 in inflammatory Rasch-built Overall Disability Scale (iRODS) score. Eligible patients who completed CIDP01 entered the open-label extension CIDP04 (NCT04051944). RESULTS: In CIDP01, between 26 March 2019 and 31 March 2021, 34 patients were randomised to rozanolixizumab or placebo (17 (50%) each). No significant difference in CFB to day 85 in iRODS centile score was observed between rozanolixizumab (least squares mean 2.0 (SE 3.2)) and placebo (3.4 (2.6); difference -1.5 (90% CI -7.5 to 4.5)). Overall, 14 (82%) patients receiving rozanolixizumab and 13 (76%) receiving placebo experienced a treatment-emergent adverse event during the treatment period. Across CIDP01 and CIDP04, rozanolixizumab was well tolerated over up to 614 days; no clinically meaningful efficacy results were seen. No deaths occurred. CONCLUSIONS: Rozanolixizumab did not show efficacy in patients with CIDP in this study, although this could be due to a relatively high placebo stability rate. Rozanolixizumab was well tolerated over medium-to-long-term weekly use, with an acceptable safety profile.
- MeSH
- chronická zánětlivá demyelinizační polyneuropatie * farmakoterapie MeSH
- dospělí MeSH
- humanizované monoklonální protilátky * terapeutické užití škodlivé účinky aplikace a dávkování MeSH
- intravenózní imunoglobuliny terapeutické užití škodlivé účinky MeSH
- jednoduchá slepá metoda MeSH
- lidé středního věku MeSH
- lidé 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: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an inflammatory disease affecting the peripheral nerves and the most frequent autoimmune polyneuropathy. Given the lack of established biomarkers or risk factors for the development of CIDP and patients' treatment response, this research effort seeks to identify potential clinical factors that may influence disease progression and overall treatment efficacy. METHODS: In this multicenter, retrospective analysis, we have screened 197 CIDP patients who presented to the University Hospitals in Düsseldorf, Berlin, Cologne, Essen, Magdeburg and Munich between 2018 and 2022. We utilized the respective hospital information system and examined baseline data with clinical examination, medical letters, laboratory results, antibody status, nerve conduction studies, imaging and biopsy findings. Aside from clinical baseline data, we analyzed treatment outcomes using the Standard of Care (SOC) definition, as well as a comparison of an early (within the first 12 months after manifestation) versus late (more than 12 months after manifestation) onset of therapy. RESULTS: In terms of treatment, most patients received intravenous immunoglobulin (56%) or prednisolone (39%) as their first therapy. Patients who started their initial treatment later experienced a worsening disease course, as reflected by a significant deterioration in their Inflammatory Neuropathy Cause and Treatment (INCAT) leg disability score. SOC-refractory patients had worse clinical outcomes than SOC-responders. Associated factors for SOC-refractory status included the presence of fatigue as a symptom and alcohol dependence. CONCLUSION: Timely diagnosis, prompt initiation of treatment and careful monitoring of treatment response are essential for the prevention of long-term disability in CIDP and suggest a "hit hard and early" treatment paradigm.
- MeSH
- chronická zánětlivá demyelinizační polyneuropatie * diagnóza terapie farmakoterapie MeSH
- dospělí MeSH
- intravenózní imunoglobuliny terapeutické užití aplikace a dávkování MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- prednisolon terapeutické užití aplikace a dávkování MeSH
- progrese nemoci MeSH
- retrospektivní 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
- multicentrická studie MeSH
There is no specific treatment for proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), a disease that is very rare in the pediatric population. We report the case of a 15-year-old boy who presented with mildly reduced kidney function and nephrotic syndrome. Kidney biopsy revealed PGNMID with monoclonal deposits of IgG3 with kappa light chain restriction. Flow cytometry showed a significant CD38 plasma cell population in the peripheral blood in the absence of other signs of hematological malignancy. The patient was treated with a 6-month course of daratumumab, a monoclonal antibody targeting CD38. There was a significant reduction in proteinuria and normalization of kidney function. Based on positive experience with adults, daratumumab should also be studied in children with PGNMID.
- MeSH
- antigeny CD38 imunologie analýza MeSH
- biopsie MeSH
- imunoglobulin G * krev MeSH
- ledviny patologie imunologie účinky léků MeSH
- lidé MeSH
- membranoproliferativní glomerulonefritida * farmakoterapie imunologie patologie MeSH
- mladiství MeSH
- monoklonální protilátky * terapeutické užití MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Termín „monoklonální gamapatie klinického významu“ (Monoclonal Gammopathy of Clinical Significance – MGCS) je zastřešující termín pro velké spektrum poruch s poškozením orgánů monoklonálními imunoglobuliny (M-Ig) či volnými lehkými řetězci (free light chain – FLC), produkovanými typicky nemaligním klonem lymfatických či plazmatických buněk. Etiopatogeneze poškození organismu je velmi pestrá, patří sem depozice M-Ig či FLC, poškození biologickou aktivitou M-Ig, asociace tvorby M-Ig s nadměrnou produkcí angiogenních a proinflamatorních cytokinů a někdy zůstává etiopatogeneze neobjasněná. Vymizení poruchy po potlačení tvorby M-Ig či FLC potvrzuje souvislost poškození s gamapatií. Některé formy MGCS poškozují dominantně jeden orgán, periferní nervy, kůži, ledviny či oči, zatímco jiné mají systémové projevy. Vyšetření M-Ig a FLC u jednotlivých poruch spolu s tkáňovými biopsiemi vedou ke stanovení diagnózy. Léčba je podobná léčbě mnohočetného myelomu či Waldenströmovy makroglobulinemie, ale na rozdíl od těchto chorob není parciální remise dostačující, cílem je dosažení kompletní remise (CR) s totálním vymizením M-Ig a FLC. Jen CR je předpokladem signifikantního zlepšení a obnovení funkce orgánů a tkání. K léčbě se používá tzv. „clone-directed therapy“, vysoce účinná antiplazmocytární či antilymfocytární léčba obsahující monoklonální protilátky (anti-CD20 nebo anti-CD38), tedy kombinace s vysokou pravděpodobností dosažení úplného vymizení M-Ig a FLC. Další léčebnou možností jsou imunomodulační dávky intravenózních imunoglobulinů (2 g/kg) podávané v 28denních intervalech. Tato terapie brzdí progresi, neodstraňuje příčinu, proto musí být podávána dlouhodobě jako udržovací léčba.
Monoclonal gammopathy of clinical significance (MGCS) is an umbrella term to describe a broad spectrum of disorders with remarkable organ dysfunctions related to the underlying non-malignant B or plasma cell clone. Although the clone itself is typically very small, it is associated with diverse clinical manifestations through different mechanisms, such as monoclonal protein deposition, the biological activity of the monoclonal immunoglobulin, or angiogenic/inflammatory cytokine hyper-secretion, or the ethiopathogensis is still unknown. Some predominantly involve a single organ, commonly peripheral nerves, kidney, skin and eye, while others are systemic diseases with syndromic presentations. Recognizing the clinical features with appropriate workups, analysis of monoclonal immunoglobulin in serum and urine and free light chain analysis in serum with particular tissue biopsies, are the key to making a timely diagnosis, especially when the kidney or skin is affected. Treatment strategy is similar to multiple myeloma or Waldenström macroglobulinemia, complete remission of gammopathy is prerequisite of significant improvement of clinical symptoms and reversal of organ dysfunctions. Therapy is based on clone-directed therapy, application of high effective antiplasmocytic or antilymphocytic therapy with monoclonal antibody (anti-CD20 or anti-CD38) with high probability of total disappearing of monoclonal immunoglobulin. Other therapeutic possibility is immunomodulation with high-dose intravenous immunoglobulin 2g/kg administered in 28days interval as maintenance therapy.
- MeSH
- antibakteriální látky terapeutické užití MeSH
- antibiotická profylaxe MeSH
- hlášení nemocí MeSH
- imunoglobulin A krev MeSH
- imunoglobulin G krev MeSH
- pertuse * diagnóza terapie MeSH
- primární prevence MeSH
- sérologické testy MeSH
- vakcína proti záškrtu, tetanu a černému kašli MeSH
- Publikační typ
- směrnice pro lékařskou praxi MeSH
