Terapie anti-CD20 monoklonálními protilátkami hraje důležitou roli v léčbě celé řady autoimunitních onemocnění. V neurologii se jedná především o relabující a primárně progresivní formy roztroušené sklerózy. Nejvýznamnější limitací léčby a nežádoucími účinky jsou hypogamaglobulinemie a recidivující bakteriální infekce. Včasná diagnóza komplikací a zahájení terapie jsou klíčové v jejich léčbě. K základním terapeutickým přístupům patří antibiotická profylaxe a imunoglobulinová substituční terapie. V indikovaných případech je možné zvažovat i očkování proti rizikovým infekcím.
Anti-CD20 monoclonal antibody therapy plays an important role in the therapy of a wide range of autoimmune diseases, such as relapsing and primarily progressive forms of multiple sclerosis in neurology. The most significant limitation of treatment and side effects are hypogammaglobulinemia and recurrent bacterial infections. Early diagnosis of complications and initiation of therapy is crucial in their treatment. Main therapeutic approaches include antibiotic prophylaxis and immunoglobulin replacement therapy. In indicated cases, it is also possible to consider vaccination against high-risk infections.
BACKGROUND: Common variable immunodeficiency (CVID) is characterized by an impaired postvaccination response, high susceptibility to respiratory tract infections, and a broad spectrum of noninfectious complications. Thus, patients with CVID may be at high risk for COVID-19, and vaccination's role in prevention is questionable. OBJECTIVE: We evaluated the clinical outcomes, safety, and dynamics of humoral and T-cell immune responses induced by the mRNA vaccine BNT162b2 in CVID. METHODS: This prospective observational cohort study focused on the clinical outcomes (proportion of infected patients and disease severity), safety (incidences of adverse events and changes in laboratory parameters), and dynamics of humoral (specific postvaccination and virus-neutralizing antibody assessment) and T-cell immune responses (anti-SARS-CoV-2-specific T-cell detection) in 21 patients with CVID after a two-dose administration of BNT162b2. The patients were observed for 6 months. RESULTS: Humoral response was observed in 52% of patients (11 of 21) at month 1 after vaccination but continuously decreased to 33.3% at month 6 (five of 15). Nevertheless, they had a remarkably lower anti-SARS-CoV-2 neutralizing antibody titer compared with healthy controls. The T-cell response was measurable in 46% of patients with CVID (six of 13) at month 1 and persisted over the study period. Mild infection occurred in three patients within the follow-up period (14.3%). The vaccine also exhibited a favorable safety profile. CONCLUSIONS: The BNT162b2 vaccine elicited a measurable antibody response in a high proportion of patients, but it was limited by low titer of virus-neutralizing antibodies and rapid waning of anti-receptor-binding domain SARS-CoV-2-specific antibodies. T-cell response was detected in one-third of patients and remained stable within the follow-up period. Vaccination has favorable safety and clinical-related outcomes in preventing severe COVID-19.
- MeSH
- Common Variable Immunodeficiency * MeSH
- COVID-19 * prevention & control MeSH
- Humans MeSH
- Antibodies, Neutralizing MeSH
- Primary Immunodeficiency Diseases * MeSH
- Prospective Studies MeSH
- Antibodies, Blocking MeSH
- Antibodies, Viral MeSH
- SARS-CoV-2 MeSH
- BNT162 Vaccine MeSH
- Vaccines * MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Observational Study MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Specific antibodies are important for post-vaccination and post-infection immune responses against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The role of antibodies in preventing and treating Coronavirus disease 2019 (COVID-19) in high-risk populations has been highlighted through the use of virus-specific monoclonal antibodies, which has raised the question of immunoglobulin replacement therapy (IRT) used in immunocompromised patients. METHODS: Virus-specific anti-receptor-binding domain (RBD) and anti-nucleocapsid protein (NCAP) antibodies (assessed using a chemiluminescence assay and virus-neutralizing antibodies (virus neutralization test against Delta and Omicron variants)) were analyzed in 20 batches of 10 % (100 mg/mL) immunoglobulin solutions for intravenous IRT from two commercially available producers between January 2022 and March 2023 for clinical use. RESULTS: Anti-RBD and anti-NCAP antibodies were detected in all 20 batches of assessed IRT solutions (mean concentrations of 2817 IU/mL and 2380 IU/mL, respectively). Notably, the concentration of the virus-specific antibodies increased continuously during the follow-up period (from 822.5 IU/mL to 4066.4 IU/mL and 102 IU/mL to 3455.9 IU/mL). These antibodies demonstrated high virus-neutralizing activity against the Delta variant (mean titers of 436 and 325) but were limited to the Omicron variant (mean titers 78 and 70). The differences observed between the two brands were not statistically significant. CONCLUSION: IRT solutions contain high concentrations of anti-SARS-CoV-2 specific antibodies, which may prevent COVID-19; however, the efficacy can be influenced by variable virus-neutralizing activities against different viral strains. Therefore, appropriate IRT should be combined with other approaches, such as vaccination or pre- and post-exposure prophylaxis. Passively transmitted specific antibodies may also lead to false-positive serological test results.
Castlemanova choroba (CD) je heterogenní skupinou onemocnění charakterizovanou především lymfadenopatií a systémovými zánětlivými projevy. Podle rozsahu rozdělujeme její formu na unicentrickou (UCD) a multicentrickou (MCD). MCD je obvykle doprovázena projevy systémové zánětlivé odpovědi zahrnujícími horečku, váhový úbytek, hepatosplenomegalii, ascites a otoky. V laboratorních nálezech se vyskytují elevace zánětlivých parametrů nebo anémie. Etiologicky může být rozvoj choroby spojený s lidským herpesvirem 8 (HHV-8) nebo se může jednat o idiopatickou formu. Centrální úlohu v patogenezi hraje interleukin 6 (IL-6). Inhibice IL-6 se ukázala jako účinná léčebná modalita. V současnosti je siltuximab, chimerická monoklonální protilátka cílená proti IL-6, jediným schváleným léčebným přípravkem indikovaným k léčbě MCD. Jeho krátkodobá i dlouhodobá účinnost a bezpečnost byly potvrzeny řadou klinických studií.
Castleman disease (CD) is a heterogeneous group of diseases characterized by lymphadenopathy and systemic inflammatory manifestations. CD can be divided into uni- (UCD) and multicentric form (MCD) according to the disease extent. MCD is usually accompanied by the features of a systemic inflammatory response including fever, weight loss, hepatosplenomegaly, ascites, and edema. In these patients, we can also observe elevation of inflammatory parameters and anemia within the laboratory assessment. Based on etiological nature, the CD can be further divided into human herpesvirus-8-associated (HHV8-associated) and idiopathic form. Interleukin 6 (IL-6) plays a central role in the disease pathogenesis. Inhibition of IL-6 has been shown to be an effective treatment modality. Currently, siltuximab, a chimeric monoclonal antibody targeting IL-6, is the only approved treatment for MCD. Its short-term and long-term efficacy and safety have been demonstrated in a few clinical studies.
BACKGROUND: Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking. OBJECTIVES: This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS. METHODS: Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs. RESULTS: The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS. CONCLUSIONS: APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
- MeSH
- Phosphatidylinositol 3-Kinase * genetics MeSH
- CTLA-4 Antigen genetics MeSH
- Class I Phosphatidylinositol 3-Kinases MeSH
- Phosphatidylinositol 3-Kinases genetics MeSH
- Humans MeSH
- Mutation MeSH
- Primary Immunodeficiency Diseases * genetics MeSH
- Registries MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Keywords
- Anakinra, canakinumab,
- MeSH
- Interleukin 1 Receptor Antagonist Protein * pharmacology therapeutic use MeSH
- Anti-Inflammatory Agents, Non-Steroidal therapeutic use MeSH
- Hereditary Autoinflammatory Diseases * diagnosis drug therapy genetics classification MeSH
- Familial Mediterranean Fever drug therapy genetics MeSH
- Adrenal Cortex Hormones therapeutic use MeSH
- Humans MeSH
- Mevalonate Kinase Deficiency drug therapy genetics MeSH
- Cryopyrin-Associated Periodic Syndromes drug therapy genetics MeSH
- Receptors, Tumor Necrosis Factor genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Imunoglobuliny zasahují do celé řady regulačních mechanismů imunitního systému od adaptivní po vrozenou imunitu. Jejich podání je tedy indikováno u širokého spektra především autoprotilátkami zprostředkovaných a imunokomplexových autoimunitních onemocnění. Ve srovnání se substituční léčbou je nutné pro dosažení imunomodulačních účinků podání vysokých dávek imunoglobulinů. I přes významný výskyt nežádoucích účinků se jedná o léčbu bezpečnou.
Immunoglobulins interfere with a broad spectrum of immune system regulatory mechanisms reaching from adaptive to innate immunity. Therefore, immunoglobulin immunomodulatory therapy is indicated in various autoantibody-mediated and immune complex autoimmune diseases. High-dose immunoglobulin regimens are necessary to reach immunomodulatory effects. Despite the significant incidence of adverse events, immunoglobulin therapy is regarded as safe.
There is a growing demand for efficient medical therapies without undesired side effects that limit their application. Targeted therapies such as deliveries of pharmacologically active compounds to a specific site of action in the human body are still a big challenge. Encapsulation is an effective tool for targeted deliveries of drugs and sensitive compounds. It has been exploited as a technique that can manage the required distribution, action and metabolism of encapsulated agents. Food supplements or functional foods containing encapsulated probiotics, vitamins, minerals or extracts are often part of therapies and currently also a consumption trend. For effective encapsulation, optimal manufacturing has to be ensured. Thus, there is a trend to develop new (or modify existing) encapsulation methods. The most-used encapsulation approaches are based on barriers made from (bio)polymers, liposomes, multiple emulsions, etc. In this paper, recent advances in the use of encapsulation in the fields of medicine, food supplements and functional foods are highlighted, with emphasis on its benefits within targeted and supportive treatments. We have focused on a comprehensive overview of encapsulation options in the field of medicine and functional preparations that complement them with their positive effects on human health.
- Publication type
- Journal Article MeSH
- Review MeSH
