United Therapeutics (United States)

company📍 Silver Spring, United States
2
Alpha-gal Syndrome Publications
6
Alpha-gal Syndrome Researchers

Associated Institutions

United Therapeutics (United Kingdom)
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Publications

Allergic response to medical products in patients with alpha-gal syndrome.

Kuravi KV, Sorrells LT, Nellis JR, Rahman F, Walters AH, et al.
The Journal of thoracic and cardiovascular surgery •

Galactose-α-1,3-galactose (alpha-gal) is a carbohydrate that is ubiquitously expressed in all mammals except for primates and humans. Patients can become sensitized to this antigen and develop alpha-gal syndrome (AGS), or a red meat allergy. Symptoms range from generalized gastroenteritis and malaise to anaphylaxis, and in endemic areas, the prevalence can be as high as 20%. Although AGS patients commonly avoid alpha-gal by avoiding meat, patients have also developed symptoms due to animal-derived medical products and devices. With the rise in transcatheter aortic valve replacement, we investigate the immunogenicity of common cardiac materials and valves. To assess the in vitro immunoglobulin E response toward common medical products, including cardiac patch materials and bioprosthetic valves in patients with AGS. Immunoblot and immunohistochemistry techniques were applied to assess immunoglobulin E reactivity to various mammalian derived tissues and medical products for patients with AGS. AGS serum showed strong reactivity to all of the commercially available, nonhuman products tested, including various decellularized cardiac patch materials and bioprosthetic aortic valves. AGS serum did not react to tissues prepared using alpha-gal knockout pigs. Despite commercial decellularization processes, alpha-gal continues to be present in animal-derived medical products, including bioprosthetic valves. Serum from patients with AGS demonstrates a strong affinity for these products in vitro. This may have serious potential implications for sensitized patients undergoing cardiac surgery, including early valve failure and accelerated coronary artery disease.

Ultrasensitive capillary electrophoretic analysis of potentially immunogenic carbohydrate residues in biologics: galactose-α-1,3-galactose containing oligosaccharides.

Szabo Z, Guttman A, Bones J, Shand RL, Meh D, et al.
Molecular pharmaceutics •

With the recent growth of the global monoclonal antibody market, ultrasensitive techniques are required for rapid analysis of possible immunogenic residues, such as galactose-α-1,3-galactose (α-1,3-Gal) on therapeutic proteins expressed in murine or CHO cell lines. We report a capillary electrophoretic approach in conjunction with exoglycosidase digestion for structural elucidation of IgG N-glycans containing the above immunogenic epitope. The method uses commercially available reagents and instrumentation, thus making it readily available for implementation and validation within the biotechnology industry. The method was first evaluated using polyclonal mouse IgG N-glycans which are known to contain α-1,3-Gal containing epitopes. High reproducibility in migration time enabled determination of GU values for five α-1,3-Gal containing structures when the data from all samples analyzed was combined. The method was successfully applied to the analysis of a NCI reference standard monoclonal antibody and two development phase monoclonal antibodies. The limit of detection and limit of quantitation were 1 and 2 μg of intact protein IgG starting material, respectively, further indicating the high sensitivity of the described method.