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Medicina (Kaunas, Lithuania) Jun 2022Chronic spontaneous urticaria (CSU) considerably alters patients' quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep,... (Review)
Review
Chronic spontaneous urticaria (CSU) considerably alters patients' quality of life, often for extended periods, due to pruriginous skin lesions, impaired sleep, unexpected development of angioedema, and failure of conventional treatments in properly controlling signs and symptoms. Recent research focused on the development of new therapeutic agents with higher efficacy. Although the production of specific immunoglobulin E (IgE) antibodies against certain allergens is not a characteristic of the disease, treatment with omalizumab, a monoclonal anti-IgE antibody, proved efficient and safe in patients with moderate to severe chronic spontaneous urticaria uncontrolled by H1-antihistamines. Ligelizumab, a high-affinity monoclonal anti-IgE antibody, may also efficiently relieve symptoms of unresponsive chronic urticaria to standard therapies. This comprehensive review aims to present recently acquired knowledge on managing chronic spontaneous urticaria with new anti-IgE antibodies. We conducted extensive research on the main databases (PubMed, Google Scholar, and Web of Science) with no restrictions on the years covered, using the search terms "anti-IgE antibodies", "omalizumab", "ligelizumab", and "chronic spontaneous urticaria". The inclusion criteria were English written articles, and the exclusion criteria were animal-related studies. ClinicalTrials.gov was also reviewed for recent relevant clinical trials related to CSU treatment. CSU is a challenging disease with a significant effect on patients' quality of life. Current therapies often fail to control signs and symptoms, and additional treatment is needed. New biologic therapies against IgE antibodies and FcεRIα receptors are currently under investigation in advanced clinical trials. We reviewed recently published data on CSU management using these novel treatments. The development of new and improved treatments for CSU will lead to a more personalized therapeutical approach for patients and provide guidance for physicians in better understanding disease mechanisms. However, some agents are still in clinical trials, and more research is needed to establish the safety and efficacy of these treatments.
Topics: Animals; Anti-Allergic Agents; Antibodies, Anti-Idiotypic; Chronic Disease; Chronic Urticaria; Humans; Immunoglobulin E; Omalizumab; Quality of Life; Urticaria
PubMed: 35744079
DOI: 10.3390/medicina58060816 -
Current Opinion in Allergy and Clinical... Oct 2021To provide the most recent insights in the use of biologicals in the treatment of patients with anaphylaxis. (Review)
Review
PURPOSE OF REVIEW
To provide the most recent insights in the use of biologicals in the treatment of patients with anaphylaxis.
RECENT FINDINGS
There is evidence that biologics such as omalizumab may be safe and effective in preventing anaphylactic reactions in patients at high risk mainly because of severe food allergy or desensitization procedures to food, airborne allergen, drugs, or hymenoptera venom.
SUMMARY
Further knowledge will guide the adoption and implementation of any new therapy including biologics for anaphylaxis according to the stratification of risk/benefits.
Topics: Allergens; Anaphylaxis; Animals; Biological Products; Desensitization, Immunologic; Drug Hypersensitivity; Humans; Hymenoptera; Insect Bites and Stings; Omalizumab
PubMed: 34320591
DOI: 10.1097/ACI.0000000000000779 -
Medicine Sep 2022Immunoglobulin G4-related disease (IgG4-RD) has recently been well recognized and Kuttner tumor is known to be a chronic sclerosing sialadenitis, representing the focal...
Immunoglobulin G4-related disease (IgG4-RD) has recently been well recognized and Kuttner tumor is known to be a chronic sclerosing sialadenitis, representing the focal manifestation of IgG4-RD, in the submandibular gland (SMG). This study is to evaluate the immunologic features of IgG4-related Kuttner tumor in the SMG. We retrospectively chose 13 patients who were confirmed as having Kuttner tumor by surgical biopsy between May 2012 and January 2019. The fine-needle aspiration cytology, serum antibody levels (anti-Ro antibodies, anti-La antibodies), IgG serum levels (total IgG and IgG4), and immunohistochemical findings for IgG and IgG4-positive plasma cells were reviewed. The cytologic results found that 7 of the 9 cases were reported as chronic sialoadenitis, and the other 3 as benign lymphoproliferative lesion. The serum levels of autoantibodies, Sjögren-syndrome-related antigen A/Ro-Ab and Sjögren-syndrome-related antigen A/Ro-La, showed all normal values of serum level. The serum level of IgG was increased in only 4 among the cases. However, the IgG4 levels were significantly increased in 11 among the cases. In all the patients who received resection of SMG, immunohistochemical findings showed all positive for IgG4-RD, with elevated numbers of IgG and IgG4-positive plasma cells. The evaluation of IgG4 serum level should be very informative for the diagnosis of this tumor before surgery. Fine-needle aspiration cytology with ultrasound guidance are not conclusive in this study. The immunological study including IgG4 serum level should be required for proper diagnosis and treatment, with clinical features of the Kuttner tumor. The level of evidence was IV.
Topics: Antibodies, Anti-Idiotypic; Autoantibodies; Chronic Disease; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Retrospective Studies; Sialadenitis
PubMed: 36107501
DOI: 10.1097/MD.0000000000030175 -
Joint Bone Spine Oct 2022To assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers...
OBJECTIVES
To assess associations between ophthalmological features and the main systemic biomarkers of primary Sjögren's Syndrome (pSS), and to identify systemic biomarkers associated with severe keratoconjunctivitis sicca (KCS) in pSS patients.
METHODS
In this cross-sectional study, data was retrospectively extracted from the monocentric cohort of the French reference centre for pSS. We analysed data from the initial visit of patients admitted for suspicion of pSS and included patients validating pSS ACR/EULAR classification criteria. Ophthalmological assessment included Schirmer's test, tear break-up time, ocular staining score (OSS), and visual analogue scale (DED-VAS) for dry eye disease (DED) symptoms. Results of minor salivary gland biopsy, unstimulated whole salivary flow rate, anti-SSA/Ro antibodies, anti-SSB/La antibodies, and rheumatoid factor (RF) were collected.
RESULTS
A total of 253 patients (245 females) with confirmed pSS, aged 56.6±13.0 years, were included, among which 37% had severe KCS. Multivariate analysis showed that the presence of anti-SSA/Ro antibodies, anti-SSB/La antibodies and RF were associated with conjunctival OSS (odds ratio-OR-=1.25 per OSS unit increase; confidence interval-CI-95%=1.05-1.49; P=0.01; OR=1.31 per OSS unit increase; CI95%=1.09-1.58, P=0.002, and OR=1.34 per OSS unit increase; CI95%=1.12-1.59; P=0.001, respectively). Both anti-SSB/La antibodies and DED-VAS ≥ 5 were significantly associated with severe KCS (OR=2.03; CI95%=1.03-4.00; P<0.05 and OR=2.52, CI95%=1.31-4.90; P<0.01, respectively).
CONCLUSION
Association between conjunctival OSS and systemic biomarkers of pSS indicate the crucial importance of conjunctival staining when pSS is suspected as a cause of DED. Conversely, patients with anti-SSB and DED-VAS ≥ 5 features should be prioritized for extensive evaluation by an ophthalmologist due to their association with severe KCS.
Topics: Antibodies, Anti-Idiotypic; Biomarkers; Cross-Sectional Studies; Female; Humans; Retrospective Studies; Rheumatoid Factor; Sjogren's Syndrome
PubMed: 35716880
DOI: 10.1016/j.jbspin.2022.105426 -
Transfusion Aug 2022Anti-CD38 antibodies such as daratumumab (DARA) are critical therapies for multiple myeloma and other diseases. Unfortunately, anti-CD38 antibodies cause panreactivity...
BACKGROUND
Anti-CD38 antibodies such as daratumumab (DARA) are critical therapies for multiple myeloma and other diseases. Unfortunately, anti-CD38 antibodies cause panreactivity in indirect antiglobulin tests (IATs), complicating blood compatibility testing. The anti-CD38 interference is most often mitigated by treating reagent red blood cells (RBCs) with dithiothreitol (DTT). However, when using the DTT method, not all RBC antibody specificities can be detected (e.g., anti-K), and the DTT method is impractical for some transfusion services. We evaluated the ability of a new anti-idiotype antibody to neutralize DARA in vitro and eliminate the anti-CD38 interference.
STUDY DESIGN AND METHODS
A recombinant monoclonal rabbit anti-DARA idiotype antibody ("anti-DARA") was generated. The ratio of anti-DARA required to neutralize DARA in spiked samples was evaluated in IATs performed in gel. IATs performed in tube were used to demonstrate that anti-DARA allows alloantibody detection in the presence of DARA. Plasma samples from 29 patients receiving DARA were treated with a fixed quantity of anti-DARA (120 μg) before performing antibody detection tests (screens) in tube.
RESULTS
Anti-DARA used at or above a 1:1 ratio with DARA eliminated the DARA interference with IATs. Anti-DARA allowed detection of both alloanti-E and alloanti-K in the presence of DARA. In 27/29 (93.1%) clinical samples, 120 μg anti-DARA was sufficient to neutralize the DARA in 100 μl patient plasma.
DISCUSSION
An anti-DARA:DARA ratio as low as 1:1 is sufficient to neutralize DARA in solution. A fixed amount of anti-DARA eliminates the anti-CD38 interference in most patient samples.
Topics: Animals; Antibodies, Monoclonal; Coombs Test; Dithiothreitol; Multiple Myeloma; Rabbits
PubMed: 35866570
DOI: 10.1111/trf.17006 -
Methods in Molecular Biology (Clifton,... 2021Sensitive and reproducible pharmacokinetic (PK) assays and immunogenicity assessment are required as part of the complex and lengthy development process for...
Sensitive and reproducible pharmacokinetic (PK) assays and immunogenicity assessment are required as part of the complex and lengthy development process for biotherapeutic proteins. Ligand binding assays (LBAs) are included in a range of approaches applied to understand the nature and properties of the drug as well as the induction of anti-drug antibodies (ADA) against the therapeutic, which can cause adverse events and loss of efficacy. Currently, most biotherapeutics are monoclonal human or humanized antibodies. Anti-idiotypic antibodies, targeting the idiotopic determinants of individual antibody drugs are recognized as perfect reagents for such LBAs. Here we describe the typical setups for these assays and how different types of anti-biotherapeutic antibodies can be used to establish selective and sensitive assays.
Topics: Antibodies, Anti-Idiotypic; Antibodies, Monoclonal, Humanized; Antibody Specificity; Biological Products; Drug Development; Drug Monitoring; Epitopes; Humans; Immunoassay; Immunoglobulin Idiotypes; Ligands; Protein Binding; Proteins
PubMed: 33420997
DOI: 10.1007/978-1-0716-1186-9_18 -
International Journal of... 2023Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40... (Review)
Review
Different monoclonal antibodies have been used for the treatment of Netherton's syndrome (NS); secukinumab (anti-IL17A), infliximab (anti-TNF-α), ustekinumab (anti p40 subunit of IL-12 and IL-23), omalizumab (anti-IgE), and dupilumab (anti-IL4 and IL13). We report two sisters with severe NS who were treated with omalizumab in one and with secukinumab in the other. In view of the therapeutic failure, treatment with dupilumab was started in both sisters. The data were analyzed 16 weeks after starting treatment with dupilumab. Treatment response was assessed using the Severity Scoring Atopic Dermatitis (SCORAD); Eczema Area and Severity Index (EASI); Pruritus Numeric Rating Scale (NSR); Netherton Area Severity Assessment (NASA) and Dermatology Life Quality Index Ichthyosis. All scores were reduced after 16 weeks of treatment with dupilumab in both patients. She maintains improvement after 18 months and 12 months of treatment, respectively. No severe adverse events were reported. Treatment with dupilumab in two sisters with NS and atopic diseases produced a marked cutaneous improvement after a failed attempt with omalizumab and secukinumab. Further studies are needed to determine which biologic therapy is the most effective in NS.
Topics: Female; Humans; Omalizumab; Netherton Syndrome; Tumor Necrosis Factor Inhibitors; Treatment Outcome; Severity of Illness Index; Double-Blind Method
PubMed: 37200480
DOI: 10.1177/03946320231172881 -
Annals of Allergy, Asthma & Immunology... Nov 2023Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have...
BACKGROUND
Patient adherence to biologic therapies is crucial for clinical benefits. Previous assessments of US patient adherence to severe asthma (SA) biologic therapies have relied on health care insurance claims data that have limitations.
OBJECTIVE
To describe real-world, specialist-reported, biologic administration and adherence among US adults with SA.
METHODS
CHRONICLE (ClinicalTrials.gov identifier: NCT03373045) is an ongoing real-world, noninterventional study of patients with SA treated by US subspecialists. Sites report date and location for all biologic administrations. We evaluated biologic (benralizumab, dupilumab, mepolizumab, omalizumab, reslizumab) adherence as the proportion of days covered (PDC) during the first 52 weeks and the mean number of days until patients received the expected number of doses for 13, 26, and 52 weeks of treatment.
RESULTS
A total of 2117 patients received biologic administrations between February 2018 and February 2022. Most patients (84%) received biologic administrations at a subspecialist site. Over time, administrations at specialist sites decreased, whereas at-home administrations increased. The median PDC was 87%; the mean number of days to receive a 52-week (364-day) equivalent number of doses was 423 for all biologics (average delay of 58 days). Dupilumab had the lowest PDC and highest mean delays in dosing across all intervals; better adherence was observed among commercially insured patients.
CONCLUSION
Patients with SA are mostly adherent to biologic therapies. Biologics with shorter dosing intervals and at-home administration had worse adherence, likely because of greater opportunities for delays. Specialist-reported administration data provide a unique perspective on biologic adherence, which may be overestimated for at-home administrations by insurance claims data.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov: NCT03373045.
Topics: Adult; Humans; Asthma; Omalizumab; Biological Products; Anti-Asthmatic Agents
PubMed: 37506846
DOI: 10.1016/j.anai.2023.07.017 -
Biotechnology Letters Feb 2021Currently, there are two categories of epidermal growth factor receptor (EGFR) antagonists, small molecule antagonists and anti-EGFR antibodies. In the current study, we...
OBJECTIVE
Currently, there are two categories of epidermal growth factor receptor (EGFR) antagonists, small molecule antagonists and anti-EGFR antibodies. In the current study, we developed a new EGFR antagonist employing the anti-idiotypic antibodies strategy.
RESULTS
First, using EGF as an antigen, through a series of immunological protocols and hybridoma technology, we obtained an anti-idiotypic antibody against EGF receptor-binding epitopes. On this basis, we screened and characterized the anti-idiotype antibodies against EGFR through competitive ELISA, co-localization analysis, competitive receptor binding analysis, and immunofluorescence. Finally, an internal image anti-idiotype antibody called FG8 was successfully prepared. Experiment result shows that FG8 inhibits EGFR-mediated signaling pathways in vitro. Additionally, FG8 inhibits liver tumor cell proliferation as well as induces tumor cell apoptosis.
CONCLUSIONS
The present study suggests that FG8 is a potential therapeutic agent for liver cancer. In addition, this study provides a novel method for the preparation of EGFR antagonists.
Topics: Antibodies, Anti-Idiotypic; Antineoplastic Agents; Apoptosis; Binding, Competitive; Cell Line, Tumor; Cell Proliferation; Enzyme-Linked Immunosorbent Assay; Epitopes; ErbB Receptors; Humans; Liver Neoplasms; Protein Binding; Signal Transduction
PubMed: 33141321
DOI: 10.1007/s10529-020-03017-6 -
Dermatologic Therapy Dec 2022Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180...
Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease, characterized by the development of autoantibodies against hemidesmosomal components BP180 and BP230. The mainstay of therapy is topical and systemic corticosteroids (CS) and immunosuppressors. As this pathology mainly involves the elderly, subjects often have numerous comorbidities that influence the clinical management. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody which has recently emerged as a promising treatment for BP in patients for whom CS are contraindicated or conventional treatments have failed to control the disease. For this study, we selected five patients who presented with corticosteroid-dependent BP with a contraindication to the use of other immunosuppressive treatments. The objectives of our study were to evaluate the effectiveness of omalizumab in controlling BP and allowing to decrease the dosage of systemic CS, assessing the effects of omalizumab on the clinical manifestations and the titers of circulating anti-BP180 and BP230 antibodies, IgE and eosinophils. A reduction in the dose of systemic CS was possible in 100% of the patients and complete resolution of the clinical picture was seen in 100% for skin lesions and in 40% for pruritus. A reduction of circulating IgE was found in 40%, anti-BP180 and BP230 IgGs were decreased in 60% and eosinophils in 80%.
Topics: Humans; Adrenal Cortex Hormones; Autoantibodies; Autoantigens; Non-Fibrillar Collagens; Omalizumab; Pemphigoid, Bullous
PubMed: 36259470
DOI: 10.1111/dth.15946