Molecular insight into Nickel(II) binding by Her2-specific IgE: a possible mechanistic insight into the pathogenesis of Type I nickel hypersensitivity

SUMMARYNickel (Ni) allergy has been reported in contact dermatitis Type IV (Ni-specific T cells mediated) and asthmatic Type I (IgE-mediated) hypersensitivities. Associations between the two hypersensitivities have been found in some patients, but the underlying mechanisms remain enigmatic. Using Her2-specific IgEs as models, we found additional binding to Ni-NTA without observable changes in binding to Her2 and that glutamine, together with the canonical Ni2+-binding histidine, could form Ni2+ binding signatures. This mechanism may underlie Type I hypersensitivity in the selection of anti-Ni2+ IgEs. This mechanism may also underlie Type IV hypersensitivity and the interaction of immunoglobulin proteins with other heavy metal ions. Our findings shed light to how Ni hypersensitivities can occur and how they can be avoided in therapeutics design, or even incorporated for biotechnological purification purposes.

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Germ-free mice exhibit mast cells with impaired functionality and gut homing and do not develop food allergy

10.1101/394213 ◽

2018 ◽

Author(s):

Martin Schwarzer ◽

Petra Hermanova ◽

Dagmar Srutkova ◽

Jaroslav Golias ◽

Tomas Hudcovic ◽

...

Keyword(s):

Food Allergy ◽

Mast Cells ◽

Specific Ige ◽

Edema Formation ◽

Germ Free ◽

Mechanistic Insight ◽

Mucosal Mast Cells ◽

Ige Mediated ◽

Low Levels ◽

Insight Into

ABSTRACTBackgroundMucosal mast cells (MC) are key players in IgE-mediated food allergy (FA). The evidence on the interaction between gut microbiota, MC and susceptibility to FA is contradictory.ObjectiveWe tested the hypothesis that commensal bacteria are essential for MC migration to the gut and their maturation impacting the susceptibility to FA.MethodsThe development and severity of FA symptoms was studied in sensitized germ-free (GF), conventional (CV) and mice mono-colonized with L. plantarum WCFS1 or co-housed with CV mice. MC were phenotypically and functionally characterized.ResultsSystemic sensitization and oral challenge of GF mice with ovalbumin led to increased levels of specific IgE in serum compared to CV mice. Remarkably, despite the high levels of sensitization, GF mice did not develop diarrhea or anaphylactic hypothermia, common symptoms of FA. In the gut, GF mice expressed low levels of the MC tissue-homing markers CXCL1 and CXCL2 and harbored fewer MC which exhibited lower levels of MC protease-1 after challenge. Additionally, MC in GF mice were less mature as confirmed by flow-cytometry and reduced edema formation after injection of degranulation-provoking compound 48/80. Co-housing of GF mice with CV mice fully restored their susceptibility to develop FA. However, this did not occur when GF mice were mono-colonized with L. plantarum.ConclusionOur results demonstrate that microbiota-induced maturation and gut-homing of MC is a critical step for the development of symptoms of experimental FA. This new mechanistic insight into microbiota-MC-FA axis can be exploited in the prevention and treatment of FA in humans.

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H2-antagonist in IgE-mediated type I hypersensitivity reactions: what literature says so far?

Clinical and Molecular Allergy ◽

10.1186/s12948-021-00143-y ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Matteo Borro ◽

Simone Negrini ◽

Andrew Long ◽

Sharon Chinthrajah ◽

Giuseppe Murdaca

Keyword(s):

Receptor Antagonist ◽

Inflammatory Responses ◽

Type I ◽

Line Therapy ◽

H2 Antagonist ◽

Amino Acid Histidine ◽

Third Line Therapy ◽

Ige Mediated ◽

Third Line ◽

Type I Hypersensitivity

AbstractHistamine is a monoamine synthesized from the amino acid histidine that is well-known for its role in IgE-mediated anaphylaxis but has shown pleiotropic effects on the immune system, especially in order to promote inflammatory responses. H1-receptor antagonist are common drugs used in mild/moderate allergic reactions whereas H2-receptor antagonist are commonly administered in gastric ulcer but showed some properties in allergy too. The EAACI guidelines for diagnosis and treatment of anaphylactic reactions recommend their use as third-line therapy in adjunct to H1-antagonists. The purpose of this article is to produce a complete summary of findings and evidence known so far about the usefulness of H2-receptor antagonist in allergic reactons.

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Metagenomic discovery of CRISPR-associated transposons

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2112279118 ◽

2021 ◽

Vol 118 (49) ◽

pp. e2112279118

Author(s):

James R. Rybarski ◽

Kuang Hu ◽

Alexis M. Hill ◽

Claus O. Wilke ◽

Ilya J. Finkelstein

Keyword(s):

Gene Editing ◽

Type I ◽

Genomic Databases ◽

Type Iv ◽

Shed Light

CRISPR-associated Tn7 transposons (CASTs) co-opt cas genes for RNA-guided transposition. CASTs are exceedingly rare in genomic databases; recent surveys have reported Tn7-like transposons that co-opt Type I-F, I-B, and V-K CRISPR effectors. Here, we expand the diversity of reported CAST systems via a bioinformatic search of metagenomic databases. We discover architectures for all known CASTs, including arrangements of the Cascade effectors, target homing modalities, and minimal V-K systems. We also describe families of CASTs that have co-opted the Type I-C and Type IV CRISPR-Cas systems. Our search for non-Tn7 CASTs identifies putative candidates that include a nuclease dead Cas12. These systems shed light on how CRISPR systems have coevolved with transposases and expand the programmable gene-editing toolkit.

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Profile of Drug Hypersensitivity Patients Hospitalized in Dr. Soetomo Hospital, Surabaya, Indonesia: Preliminary Data of 6 Months Observation

Folia Medica Indonesiana ◽

10.20473/fmi.v55i1.24387 ◽

2021 ◽

Vol 55 (1) ◽

pp. 54

Author(s):

Nur Moya Isyroqiyyah ◽

Gatot Soegiarto ◽

Yuani Setiawati

Keyword(s):

Hypersensitivity Reaction ◽

Drug Hypersensitivity ◽

Demographic Data ◽

Stevens Johnson Syndrome ◽

Type I ◽

Type Iv ◽

Drug Eruptions ◽

Johnson Syndrome ◽

Drug Hypersensitivity Reaction ◽

Type I Hypersensitivity

Drug hypersensitivity is defined as an untoward response to medication which is noxious and unintended, and which occurs at doses normally used in human either for the prophylaxis, diagnosis, or therapy of disease or for the modification of physiological function. Drug hypersensitivity is common and may cause emergency condition until death. The incidence of drug hypersensitivity-related hospitalizations has usually been assessed within hospitals. The aim of this study is to determine the profile of drug hypersensitivity patients hospitalized at Dr. Soetomo Hospital in 6 months period from January to June 2016. This study was a descriptive retrospective study on medical records of drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital in 6 months period. The patient’s demographic data, the type of hypersensitivity reaction, and the final outcome of the hospitalization were collected. Within the 6 months period, there were 16 drug hypersensitivity patients hospitalized in Dr. Soetomo Hospital. Most of them are female (56.25%), and aged between 46-55 years (25%). There were 4 patients (25%) with type I hypersensitivity: urticaria, angioedema and anaphylaxis; while type IV hypersensitivity occured in 12 patients (75%): Stevens-Johnson syndrome, Stevens-Johnson syndrome-Toxic Epidermal Necrolysis overlap, erythroderma, maculopapular drug eruptions, and DRESS. Most of the patients (87.5%) had favorable outcome after hospitalization. There were 16 patients with drug hypersensitivity reaction hospitalized in Dr. Soetomo Hospital, Surabaya in 6 months period. Most of them were female and had type IV hypersensitivity reactions.

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Disabling a Type I-E CRISPR-Cas Nuclease with a Bacteriophage-Encoded Anti-CRISPR Protein

mBio ◽

10.1128/mbio.01751-17 ◽

2017 ◽

Vol 8 (6) ◽

Cited By ~ 31

Author(s):

April Pawluk ◽

Megha Shah ◽

Marios Mejdani ◽

Charles Calmettes ◽

Trevor F. Moraes ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Transcriptional Repressor ◽

Mobile Genetic Elements ◽

Type I ◽

Genetic Studies ◽

Genetic Elements ◽

Crispr System ◽

Mechanistic Insight ◽

Resistance To Invasion ◽

Insight Into

ABSTRACT CRISPR (clustered regularly interspaced short palindromic repeat)-Cas adaptive immune systems are prevalent defense mechanisms in bacteria and archaea. They provide sequence-specific detection and neutralization of foreign nucleic acids such as bacteriophages and plasmids. One mechanism by which phages and other mobile genetic elements are able to overcome the CRISPR-Cas system is through the expression of anti-CRISPR proteins. Over 20 different families of anti-CRISPR proteins have been described, each of which inhibits a particular type of CRISPR-Cas system. In this work, we determined the structure of type I-E anti-CRISPR protein AcrE1 by X-ray crystallography. We show that AcrE1 binds to the CRISPR-associated helicase/nuclease Cas3 and that the C-terminal region of the anti-CRISPR protein is important for its inhibitory activity. We further show that AcrE1 can convert the endogenous type I-E CRISPR system into a programmable transcriptional repressor. IMPORTANCE The CRISPR-Cas immune system provides bacteria with resistance to invasion by potentially harmful viruses, plasmids, and other foreign mobile genetic elements. This study presents the first structural and mechanistic insight into a phage-encoded protein that inactivates the type I-E CRISPR-Cas system in Pseudomonas aeruginosa. The interaction of this anti-CRISPR protein with the CRISPR-associated helicase/nuclease proteins Cas3 shuts down the CRISPR-Cas system and protects phages carrying this gene from destruction. This interaction also allows the repurposing of the endogenous type I-E CRISPR system into a programmable transcriptional repressor, providing a new biotechnological tool for genetic studies of bacteria encoding this type I-E CRISPR-Cas system. IMPORTANCE The CRISPR-Cas immune system provides bacteria with resistance to invasion by potentially harmful viruses, plasmids, and other foreign mobile genetic elements. This study presents the first structural and mechanistic insight into a phage-encoded protein that inactivates the type I-E CRISPR-Cas system in Pseudomonas aeruginosa. The interaction of this anti-CRISPR protein with the CRISPR-associated helicase/nuclease proteins Cas3 shuts down the CRISPR-Cas system and protects phages carrying this gene from destruction. This interaction also allows the repurposing of the endogenous type I-E CRISPR system into a programmable transcriptional repressor, providing a new biotechnological tool for genetic studies of bacteria encoding this type I-E CRISPR-Cas system.

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Non-Invasive Human Embryo Metabolic Assessment as a Developmental Criterion

Journal of Clinical Medicine ◽

10.3390/jcm9124094 ◽

2020 ◽

Vol 9 (12) ◽

pp. 4094

Author(s):

Marjan Motiei ◽

Katerina Vaculikova ◽

Andrea Cela ◽

Katerina Tvrdonova ◽

Reza Khalili ◽

...

Keyword(s):

Multiple Pregnancy ◽

Essential Amino Acids ◽

Blastocyst Development ◽

Non Invasive ◽

Metabolomic Profiling ◽

Mechanistic Insight ◽

Qualitative Technique ◽

Insight Into ◽

Selection Of ◽

Multiple Pregnancy Rate

The selection of a highly-viable single embryo in assisted reproductive technology requires an acceptable predictive method in order to reduce the multiple pregnancy rate and increase the success rate. In this study, the metabolomic profiling of growing and impaired embryos was assessed on the fifth day of fertilization using capillary electrophoresis in order to find a relationship between the profiling and embryo development, and then to provide a mechanistic insight into the appearance/depletion of the metabolites. This unique qualitative technique exhibited the appearance of most non-essential amino acids and lactate, and depleting the serine, alanyl-glutamine and pyruvate in such a manner that the embryos impaired in their development secreted a considerably higher level of lactate and consumed a significantly higher amount of alanyl-glutamine. The different significant ratios of metabolomic depletion/appearance between the embryos confirm their potential for the improvement of the prospective selection of the developed single embryos, and also suggest the fact that pyruvate and alanyl-glutamine are the most critical ATP suppliers on the fifth day of blastocyst development.

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Antibiotic Hypersensitivity Mechanisms

Pharmacy ◽

10.3390/pharmacy7030122 ◽

2019 ◽

Vol 7 (3) ◽

pp. 122 ◽

Cited By ~ 3

Author(s):

Jenana H. Maker ◽

Cassandra M. Stroup ◽

Vanthida Huang ◽

Stephanie F. James

Keyword(s):

Bacterial Infections ◽

Signs And Symptoms ◽

Type I ◽

Hypersensitivity Reactions ◽

Type Iv ◽

Immune Mediated ◽

Different Types ◽

Ige Mediated ◽

Antibiotic Reactions ◽

Immune Complex Formation

Antibiotics are commonly prescribed to treat a variety of bacterial infections. As with all medications, hypersensitivity reactions may occur and clinicians should be able to recognize them accurately and recommend appropriate management. Antibiotic related hypersensitivity reactions may be one of four different types: Type I reactions, which are IgE mediated and may lead to anaphylaxis; Type II reactions that are antibody-mediated and may result in thrombocytopenia, neutropenia, or hemolytic anemia; Type III reaction that involves an immune complex formation such as vasculitis; and Type IV reactions that consist of four subtypes and typically include a rash of varying level of severity with or without systemic signs and symptoms. Herein, we describe the mechanisms of different types of allergic reactions to commonly prescribed antibiotics and offer recommendations for management. Further, we briefly refer to antibiotic reactions that mimic hypersensitivity reactions but are not immune mediated, such as pseudoallergies and serum sickness-like reactions.

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Morin inhibits Fyn kinase in mast cells and IgE-mediated type I hypersensitivity response in vivo

Biochemical Pharmacology ◽

10.1016/j.bcp.2009.01.019 ◽

2009 ◽

Vol 77 (9) ◽

pp. 1506-1512 ◽

Cited By ~ 50

Author(s):

Jie Wan Kim ◽

Jun Ho Lee ◽

Bang Yeon Hwang ◽

Se Hwan Mun ◽

Na Young Ko ◽

...

Keyword(s):

Mast Cells ◽

Type I ◽

Hypersensitivity Response ◽

Fyn Kinase ◽

Ige Mediated ◽

Type I Hypersensitivity

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Organizational culture: a foundational perspective

African Journal of Economic and Management Studies ◽

10.1108/ajems-06-2016-0085 ◽

2017 ◽

Vol 8 (3) ◽

pp. 262-273 ◽

Cited By ~ 2

Author(s):

Charlotte Pietersen

Keyword(s):

Organizational Culture ◽

Organizational Behavior ◽

Type I ◽

Content Type ◽

Fundamental Knowledge ◽

Type Iv ◽

Documentary Analysis ◽

Research Orientations ◽

Applicable Knowledge ◽

Selection Of

Purpose The purpose of this paper is to perform a typological analysis of research orientations in the field of organizational culture (OC) in order to provide a broad, original perspective on the nature of research in this field, beyond the current quantitative/qualitative dichotomy. Design/methodology/approach Documentary analysis, consisting of a content analysis of an appropriate and conceptually convenient selection of 200 source publications, was conducted. The analysis was performed in terms of four fundamental knowledge orientations and methodologies. Findings An analysis and description of the chosen set of examples for each of the four types of knowledge showed that, as with other areas in the field of organizational behavior and management (and also other scholarly disciplines), the typology finds clear expression in the area of OC. Research limitations/implications In view of the aim and originality of the present paper, the sample size employed is not a worrying factor as sufficient and clear examples of each of the four basic types of research orientations have been provided. It is recommended that the broadly applicable knowledge (and by implication research) orientations that were introduced here, be considered by OC researchers. The analysis of fundamental approaches to research provides an inclusive perspective on the nature of different ways of studying and understanding OC. This should assist in expanding both scholarly and practitioner horizons. It is concluded that the analysis of research in the field of OC in terms of fundamental types of human knowledge provides a unique and expanded view on research in this area. Practical implications All stakeholders in the field of human resource management could benefit from taking cognizance of a broader perspective of knowledge development in the field of OC. The four-fold framework could also be utilized as a valuable source for restructuring and teaching of research methodology programs and courses in institutions of higher education, especially concerning the general need for greater attention to: theoretical (type I), and evaluation (type IV) research in management and organizational behavior. Originality/value The analysis of fundamental knowledge orientations provides an original and encompassing perspective on the nature of different approaches to the study and understanding of OC.

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Molecular Insights of Nickel Binding to Therapeutic Antibodies as a Possible New Antibody Superantigen

Frontiers in Immunology ◽

10.3389/fimmu.2021.676048 ◽

2021 ◽

Vol 12 ◽

Author(s):

Chinh Tran-To Su ◽

Wai-Heng Lua ◽

Jun-Jie Poh ◽

Wei-Li Ling ◽

Joshua Yi Yeo ◽

...

Keyword(s):

Underlying Mechanism ◽

Light Chains ◽

Common Mechanism ◽

Type I ◽

Therapeutic Antibodies ◽

Type Iv ◽

Nickel Binding ◽

Heavy Chain Constant Region ◽

Complementarity Determining Regions ◽

Type I Hypersensitivity

The binding of nickel by immune proteins can manifest as Type IV contact dermatitis (Ni-specific T cells mediated) and less frequently as Type I hypersensitivity with both mechanisms remaining unknown to date. Since there are reports of patients co-manifesting the two hypersensitivities, a common mechanism may underlie both the TCR and IgE nickel binding. Focusing on Trastuzumab and Pertuzumab IgE variants as serendipitous investigation models, we found Ni-NTA interactions independent of Her2 binding to be due to glutamine stretches. These stretches are both Ni-inducible and in fixed pockets at the antibody complementarity-determining regions (CDRs) and framework regions (FWRs) of both the antibody heavy and light chains with influence from the heavy chain constant region. Comparisons with TCRs structures revealed similar interactions, demonstrating the possible underlying mechanism in selecting for Ni-binding IgEs and TCRs respectively. With the elucidation of the interaction, future therapeutic antibodies could also be sagaciously engineered to utilize such nickel binding for biotechnological purposes.

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