Accurate assessment of alpha‐gal syndrome using cetuximab and bovine thyroglobulin‐specific IgE

Sim, Da Woon; Lee, Jong Sun; Park, Kyung Hee; Jeong, Kyoung Yong; Ye, Young-Min; Lee, Jae Hyun

doi:10.1002/mnfr.201601046

Cited by 14 publications

(15 citation statements)

References 41 publications

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“…We also show that Tc-bovine antibodies have similar levels of α-gal compared with a human-derived IVIG. The α-gal causes a human-immunologic barrier to xenotransplantation or anaphylaxis/hypersensitivity reactions in some humans after equine antivenom or cetuximab administration or red meat consumption, and SAB-139 should not cause α-gal-related reactions [7,8,39]. Results from the recently completed phase I clinical trial in healthy adults for SAB-301 (anti-MERS CoV) [18] indicated that it was well tolerated, but further studies in humans to determine safety and/or immunogenicity will be needed for SAB-139 and other Tc-hIgG products.…”

Section: Discussionmentioning

confidence: 99%

“…Several passive immunotherapeutics are under development to treat emerging infectious diseases and filoviruses [1][2][3][4][5][6]. However, traditional human-derived and heterologous animal-derived polyclonal immunoglobulins (Igs) and monoclonal antibodies can have lengthy development and/or clinical safety issues [1,7,8]. To address these shortcomings, genetically modified transchromosomic bovines (Tc-bovines) were developed that adaptively produce fully human polyclonal antibodies after exposure to environmental or vaccine antigens [9][10][11][12].…”

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confidence: 99%

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Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Luke

Bennett

Gerhardt

et al. 2018

The Journal of Infectious Diseases

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Transchromosomic bovines (Tc-bovines) adaptively produce fully human polyclonal immunoglobulin (Ig)G antibodies after exposure to immunogenic antigen(s). The National Interagency Confederation for Biological Research and collaborators rapidly produced and then evaluated anti-Ebola virus IgG immunoglobulins (collectively termed SAB-139) purified from Tc-bovine plasma after sequential hyperimmunization with an Ebola virus Makona isolate glycoprotein nanoparticle vaccine. SAB-139 was characterized by several in vitro production, research, and clinical level assays using wild-type Makona-C05 or recombinant virus/antigens from different Ebola virus variants. SAB-139 potently activates natural killer cells, monocytes, and peripheral blood mononuclear cells and has high-binding avidity demonstrated by surface plasmon resonance. SAB-139 has similar concentrations of galactose-α-1,3-galactose carbohydrates compared with human-derived intravenous Ig, and the IgG1 subclass antibody is predominant. All rhesus macaques infected with Ebola virus/H.sapiens-tc/GIN/2014/Makona-C05 and treated with sufficient SAB-139 at 1 day (n = 6) or 3 days (n = 6) postinfection survived versus 0% of controls. This study demonstrates that Tc-bovines can produce pathogen-specific human Ig to prevent and/or treat patients when an emerging infectious disease either threatens to or becomes an epidemic.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Luke

Bennett

Gerhardt

et al. 2018

The Journal of Infectious Diseases

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“…* A definitive association between these tick species and AGS has not been experimentally proven in all these reports [see van Nunen (31)] .** The study by Sim et al (72) reported 11 cases of AGS, Lee et al (71) reported 1 case of AGS and van Nunen (44) reported that several more cases of this disease have occurred in Korea .…”

Section: Epidemiology Of Agsmentioning

confidence: 99%

Environmental and Molecular Drivers of the α-Gal Syndrome

et al. 2019

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The α-Gal syndrome (AGS) is a type of allergy characterized by an IgE antibody (Ab) response against the carbohydrate Galα1-3Galβ1-4GlcNAc-R (α-Gal), which is present in glycoproteins from tick saliva and tissues of non-catarrhine mammals. Recurrent tick bites induce high levels of anti-α-Gal IgE Abs that mediate delayed hypersensitivity to consumed red meat products in humans. This was the first evidence that tick glycoproteins play a major role in allergy development with the potential to cause fatal delayed anaphylaxis to α-Gal-containing foods and drugs and immediate anaphylaxis to tick bites. Initially, it was thought that the origin of tick-derived α-Gal was either residual blood meal mammalian glycoproteins containing α-Gal or tick gut bacteria producing this glycan. However, recently tick galactosyltransferases were shown to be involved in α-Gal synthesis with a role in tick and tick-borne pathogen life cycles. The tick-borne pathogen Anaplasma phagocytophilum increases the level of tick α-Gal, which potentially increases the risk of developing AGS after a bite by a pathogen-infected tick. Two mechanisms might explain the production of anti-α-Gal IgE Abs after tick bites. The first mechanism proposes that the α-Gal antigen on tick salivary proteins is presented to antigen-presenting cells and B-lymphocytes in the context of Th 2 cell-mediated immunity induced by tick saliva. The second mechanism is based on the possibility that tick salivary prostaglandin E2 triggers Immunoglobulin class switching to anti-α-Gal IgE-producing B cells from preexisting mature B cells clones producing anti-α-Gal IgM and/or IgG. Importantly, blood group antigens influence the capacity of the immune system to produce anti-α-Gal Abs which in turn impacts individual susceptibility to AGS. The presence of blood type B reduces the capacity of the immune system to produce anti-α-Gal Abs, presumably due to tolerance to α-Gal, which is very similar in structure to blood group B antigen. Therefore, individuals with blood group B and reduced levels of anti-α-Gal Abs have lower risk to develop AGS. Specific immunity to tick α-Gal is linked to host immunity to tick bites. Basophil activation and release of histamine have been implicated in IgE-mediated acquired protective immunity to tick infestations and chronic itch. Basophil reactivity was also found to be higher in patients with AGS when compared to asymptomatic α-Gal sensitized individuals. In addition, host resistance to tick infestation is associated with resistance to tick-borne pathogen infection. Anti-α-Gal IgM and IgG Abs protect humans against vector-borne pathogens and blood group B individuals seem to be more susceptible to vector-borne diseases. The link between blood groups and anti-α-Gal immunity which in turn affects resistance to vector-borne pathogens and susceptibility to AGS, suggests a trade-off between susceptibility to AGS and protection to some infectious diseases. The understanding of the environmental and mole...

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“…SPT and sIgE for crude meat extracts such as beef, pork or lamb are known to be not valuable for the differential diagnosis of α-gal syndrome 27. Contrarily, sIgE for α-gal is known to have diagnostic value in α -gal syndrome 28. PROTIA™ Allergy-Q 64 Atopy ® detects IgE for α-gal using bovine thyroglobulin (bTG).…”

Section: Discussionmentioning

confidence: 99%

Validation of PROTIA™ Allergy-Q 64 Atopy^® as a Specific IgE Measurement Assay for 10 Major Allergen Components

Kim

Park

Lee

et al. 2019

Allergy Asthma Immunol Res

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Purpose Component-resolved diagnostics (CRD) is expected to provide additional diagnostic information in allergic patients. PROTIA™ Allergy-Q 64 Atopy ® , a recently developed CRD-based multiplex specific immunoglobulin E (sIgE) assay, can quantitatively measure sIgE to major allergen components. Methods The sIgE detection by PROTIA™ Allergy-Q 64 Atopy ® and ImmunoCAP ® assays was compared using the sera of 125 Korean allergic patients. Group 1 and 2 allergens of house dust mites (HDMs; Dermatophagoides farinae (Der f) 1 and Der f 2 in PROTIA™ Allergy-Q 64 Atopy ® , Dermatophagoides pteronyssinus (Der p) 1 and Der p 2 in ImmunoCAP ® ), Bet v 1, Fel d 1, Que a 1, ω-5 gliadin, α-lactalbumin, β-lactoglobulin, casein and α-Gal were measured by both assays. Results Comparing the results from the 2 assays, the agreement rate for all the 10 allergens was > 88% (group 1 HDM allergen, 100%; group 2 HDM allergen, 94.6%; Bet v 1, 97.4%; Fel d 1, 90.5%; Que a 1, 89.2%; α-lactalbumin, 96%; β-lactoglobulin, 88%; casein, 88%; ω-5 gliadin, 96%; α-Gal, 100%). Correlation analysis indicated that, all the 10 allergen sIgEs showed more than moderate positive correlation (Pearson correlation coefficients > 0.640). Additionally, intra-class comparison showed more than high correlation for all the 10 allergens (Spearman's rank correlation coefficients > 0.743). Conclusions PROTIA™ Allergy-Q 64 Atopy ® is reliable and comparable to the ImmunoCAP ® assay for component-resolved diagnosis.

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Accurate assessment of alpha‐gal syndrome using cetuximab and bovine thyroglobulin‐specific IgE

Abstract: Differentiation of alpha-gal syndrome from patients with immediate allergy to meat consumption or asymptomatic sensitization requires quantification of cetuximab- or BTG-induced sIgE via detection of IgE for α-gal.

Cited by 14 publications

References 41 publications

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Environmental and Molecular Drivers of the α-Gal Syndrome

Validation of PROTIA™ Allergy-Q 64 Atopy^® as a Specific IgE Measurement Assay for 10 Major Allergen Components

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Accurate assessment of alpha‐gal syndrome using cetuximab and bovine thyroglobulin‐specific IgE

Abstract: Differentiation of alpha-gal syndrome from patients with immediate allergy to meat consumption or asymptomatic sensitization requires quantification of cetuximab- or BTG-induced sIgE via detection of IgE for α-gal.

Cited by 14 publications

References 41 publications

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Fully Human Immunoglobulin G From Transchromosomic Bovines Treats Nonhuman Primates Infected With Ebola Virus Makona Isolate

Environmental and Molecular Drivers of the α-Gal Syndrome

Validation of PROTIA™ Allergy-Q 64 Atopy® as a Specific IgE Measurement Assay for 10 Major Allergen Components

Contact Info

Product

Resources

About

Validation of PROTIA™ Allergy-Q 64 Atopy^® as a Specific IgE Measurement Assay for 10 Major Allergen Components