scholarly journals How to Prevent and Mitigate Hypersensitivity Reactions to Biologicals Induced by Anti-Drug Antibodies?

2021 ◽  
Vol 12 ◽  
Author(s):  
Alessandra Vultaggio ◽  
Margherita Perlato ◽  
Francesca Nencini ◽  
Emanuele Vivarelli ◽  
Enrico Maggi ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cytokine Production ◽  
Inflammatory Diseases ◽  
Immunosuppressive Treatment ◽  
Complex Structures ◽  
Hypersensitivity Reactions ◽  
Immediate Hypersensitivity ◽  
Rheumatologic Diseases ◽  
Ige Mediated ◽  
Underlying Mechanisms

Biologicals are widely used therapeutic agents for rheumatologic diseases, cancers, and other chronic inflammatory diseases. They are characterized by complex structures and content of variable amounts of foreign regions, which may lead to anti-drug antibodies (ADA) development. ADA onset may limit the clinical usage of biologicals because they may decrease their safety. In fact they are mainly associated with immediate hypersensitivity reactions (HSRs). Development of ADAs is reduced by concomitant immunosuppressive treatment, while it is increased by longer intervals between drug administrations; thus, regular infusion regimens should be preferred to reduce HSRs. Once ADAs have formed, some procedures can be implemented to reduce the risk of HSRs. ADAs may belong to different isotype; the detection of IgE ADA is advisable to be assessed when high and early ADAs are detected, in order to reduce the risk of severe HRs. In patients who need to reintroduce the biological culprit, as alternative therapies are not available, drug desensitization (DD) may be applied. Desensitization should be conceptually dedicated to patients with an IgE-mediated HSR; however, it can be performed also in patients who had developed non-IgE-mediated HSRs. Although the underlying mechanisms behind successful DD has not been fully clarified, the DD procedure is associated with the inhibition of mast cell degranulation and cytokine production. Additionally, some data are emerging about the inhibition of drug-specific immune responses during DD.

scholarly journals Mutual Interplay of Host Immune System and Gut Microbiota in the Immunopathology of Atherosclerosis

2020 ◽  
Vol 21 (22) ◽  
pp. 8729 ◽  
Author(s):  
Chih-Fan Yeh ◽  
Ying-Hsien Chen ◽  
Sheng-Fu Liu ◽  
Hsien-Li Kao ◽  
Ming-Shiang Wu ◽  
...  
Keyword(s):  
Immune System ◽  
Immune Responses ◽  
Cytokine Production ◽  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Inflammasome Activation ◽  
Host Immune System ◽  
Gut Permeability ◽  
And Function ◽  
Progression Of Atherosclerosis

Inflammation is the key for the initiation and progression of atherosclerosis. Accumulating evidence has revealed that an altered gut microbiome (dysbiosis) triggers both local and systemic inflammation to cause chronic inflammatory diseases, including atherosclerosis. There have been some microbiome-relevant pro-inflammatory mechanisms proposed to link the relationships between dysbiosis and atherosclerosis such as gut permeability disruption, trigger of innate immunity from lipopolysaccharide (LPS), and generation of proatherogenic metabolites, such as trimethylamine N-oxide (TMAO). Meanwhile, immune responses, such as inflammasome activation and cytokine production, could reshape both composition and function of the microbiota. In fact, the immune system delicately modulates the interplay between microbiota and atherogenesis. Recent clinical trials have suggested the potential of immunomodulation as a treatment strategy of atherosclerosis. Here in this review, we present current knowledge regarding to the roles of microbiota in contributing atherosclerotic pathogenesis and highlight translational perspectives by discussing the mutual interplay between microbiota and immune system on atherogenesis.

scholarly journals Successful olaparib desensitization using a novel one-day protocol

2020 ◽  
Vol 16 (1) ◽  
Author(s):  
Rongbo Zhu ◽  
Stephen Welch ◽  
Hannah Roberts
Keyword(s):  
Adverse Reactions ◽  
Chemotherapeutic Agents ◽  
Hypersensitivity Reactions ◽  
Immediate Hypersensitivity ◽  
Case Presentation ◽  
Tablet Form ◽  
Desensitization Protocol ◽  
Ige Mediated ◽  
Loss Of Tolerance

Abstract Background Olaparib is a revolutionary treatment for patients with ovarian and breast cancer. Currently, there is no established 1-day drug desensitization protocol for patients with olaparib type-1 hypersensitivity reactions despite well documented IgE-mediated adverse reactions occurring with olaparib. Case presentation We report a 58-year-old female with immediate, reproducible IgE-mediated adverse reactions to olaparib tablets with implementation of a 1-day novel desensitization protocol to olaparib. Following desensitization, the patient was successfully transitioned from olaparib capsules to tablets with no loss of tolerance. Conclusions To our knowledge, this is the first reported case of successful olaparib desensitization using a novel 1-day desensitization protocol, and will contribute to drug allergy knowledge, in an area where robust data is lacking. This case demonstrates the important role for drug desensitization in patients with immediate hypersensitivity reactions to chemotherapeutic agents. Furthermore, as olaparib capsules are being phased out in favour of olaparib tablets, we provide a clear case that transitioning from capsule to tablet form did not cause a loss of tolerance.

Hypersensitivity diseases

2018 ◽  
Author(s):  
Malini Bhole
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Complex Disease ◽  
Organ Damage ◽  
Type I ◽  
Hypersensitivity Reactions ◽  
Type Ii ◽  
Immune Complex Disease ◽  
Immediate Hypersensitivity ◽  
Type Iv

Hypersensitivity reactions are aberrant immune responses that are provoked by innocuous extrinsic or self-antigens, are mediated by B-cells or T-cells, and may result in tissue or organ damage. Coombs and Gell classified hypersensitivity reactions into four types, based on the different immune responses: type I, or immediate hypersensitivity; type II, or antibody-mediated (humoral) cytotoxicity; type III, or immune-complex disease; and type IV, or delayed hypersensitivity. This chapter reviews the clinical features, diagnosis, and management of hypersensitivity reactions.

scholarly journals Cardamonin Inhibits Oxazolone-Induced Atopic Dermatitis by the Induction of NRF2 and the Inhibition of Th2 Cytokine Production

Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 834
Author(s):  
Ok-Kyung Yoo ◽  
Won Jun Choi ◽  
Young-Sam Keum
Keyword(s):  
Atopic Dermatitis ◽  
Immune Responses ◽  
Immune Cells ◽  
Natural Compound ◽  
Cytokine Production ◽  
Hypersensitivity Reactions ◽  
Connective Tissues ◽  
Oxidative Damages ◽  
Th2 Cytokine

The skin is constantly exposed to various types of chemical stresses that challenge the immune cells, leading to the activation of T cell-mediated hypersensitivity reactions including atopic dermatitis. Previous studies have demonstrated that a variety of natural compounds are effective against development of atopic dermatitis by modulating immune responses. Cardamonin is a natural compound abundantly found in cardamom spices and many other medicinal plant species. In the present study, we attempted to examine whether cardamonin could inhibit oxazolone-induced atopic dermatitis in vivo. Our results show that topical application of cardamonin onto the ear of mice suppressed oxazolone-induced inflammation in the ear and hyperplasia in the spleen. Cardamonin also inhibited oxazolone-induced destruction of connective tissues and subsequent infiltration of mast cells into the skin. In addition, we found that the production of Th2 cytokines is negatively regulated by NRF2, and the induction of NRF2 by cardamonin contributed to suppressing oxazolone-induced Th2 cytokine production and oxidative damages in vivo. Together, our results demonstrate that cardamonin is a promising natural compound, which might be effective for treatment of atopic dermatitis.

scholarly journals GATA-2–deficient mast cells limit IgE-mediated immediate hypersensitivity reactions in human subjects

2019 ◽  
Vol 144 (2) ◽  
pp. 613-617.e14 ◽  
Author(s):  
Avanti Desai ◽  
Kathryn Sowerwine ◽  
Yihui Liu ◽  
Monica G. Lawrence ◽  
Jack Chovanec ◽  
...  
Keyword(s):  
Mast Cells ◽  
Human Subjects ◽  
Hypersensitivity Reactions ◽  
Immediate Hypersensitivity ◽  
Ige Mediated

scholarly journals Hypersensitivity Reactions to Biologicals: an EAACI position paper

2021 ◽  
Author(s):  
Sevim Bavbek ◽  
Mauro Pagani ◽  
Emilio Alvarez-Cuesta ◽  
Mariana Castells ◽  
Adile Berna Dursun ◽  
...  
Keyword(s):  
Unmet Needs ◽  
Inflammatory Diseases ◽  
Treatment Options ◽  
Position Paper ◽  
Hypersensitivity Reactions ◽  
Future Studies ◽  
High Prevalence ◽  
Lifetime Exposure ◽  
New Treatment ◽  
Underlying Mechanisms

Because of their selectivity, biologicals are crucial therapeutic agents in oncological, immunological, and inflammatory diseases and their use in clinical practice is broadening. Biologicals are among the most common drugs that can cause hypersensitivity reactions (HSRs), and this is primarily attributed to an explosion in new treatment options that has developed through personalized and precision medicine. Patients can develop HSRs to these agents during the first lifetime exposure or after repeated exposure. Despite its relatively high prevalence, the underlying mechanisms and optimal management of HSRs to biologicals remain incompletely explained. In this position paper, the authors provided evidence-based recommendations for the diagnosis and management of HSRs to biologicals. Additionally, the document defines unmet needs, which should be topics of future studies.

Evaluation of Hypersensitivity Reactions in Pediatric Patients Using Biological Drugs

2021 ◽  
pp. 1-8
Author(s):  
Ozge Yilmaz Topal ◽  
Volkan Kose ◽  
Banu Acar ◽  
Umut Selda Bayrakci ◽  
Derya Ozyoruk ◽  
...  
Keyword(s):  
Pediatric Patients ◽  
Additional Treatment ◽  
Hypersensitivity Reactions ◽  
Biological Drugs ◽  
Rheumatologic Diseases ◽  
Culprit Drug ◽  
Dose Infusion ◽  
History Of ◽  
Oncologic Diseases ◽  
Biologic Drug

<b><i>Introduction:</i></b> Biological drugs are currently used for the treatment of chronic inflammatory, autoimmune, and neoplastic diseases. With their expanding indication spectrum and increasing use, hypersensitivity reactions to these drugs are also becoming more frequent. The present study aimed to report the incidence and the features of such reactions in pediatric patients using biologicals for the treatment of various diseases. <b><i>Methods:</i></b> The medical records of pediatric patients treated with biological agents between October 1, 2011 and August 31, 2019 were reviewed and adverse reactions were evaluated retrospectively. <b><i>Results:</i></b> During the study period, 211 patients (116 boys, 55%) used 21 different biological drugs for the treatment of various diseases. Their median age at the time of the first treatment was 139.9 (IQR: 92.2–187.8) months. Hematologic-oncologic diseases were the most common indication for biological therapy (97/211; 46.0%), followed by rheumatologic diseases (82/211; 38.9%). Of the 211 patients, 14 (6.64%) experienced reactions to biological drugs. The most common culprit agent was rituximab (57.1%). Most of the patients (85.7%) had a history of reactions either during the infusion or within 1 h after taking the drug. Five patients underwent desensitization to the culprit drug, while 7 other patients continued treatment with a reduced dose/infusion rate or premedication. Also 1 patient continued to take the drug without any additional treatment. <b><i>Conclusion:</i></b> It was reported that 6.64% of the patients who received biologic drug therapy for various reasons in our hospital had hypersensitivity. The most common culprit agent was rituximab, and most of the reactions were immediate reactions.

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