University of Nebraska–Lincoln

Chronic low back pain (LBP) is a leading cause of disability, but treatments for LBP are limited. Degeneration of the intervertebral disc due to loss of neuroinhibitory sulfated glycosaminoglycans (sGAGs) allows nerves from dorsal root ganglia to grow into the core of the disc. Treatment with a decellularized tissue hydrogel that contains sGAGs may inhibit nerve growth and prevent disc-associated LBP. A protocol to decellularize porcine nucleus pulposus (NP) was adapted from previous methods. DNA, sGAG, α-gal antigen, and collagen content were analyzed before and after decellularization. The decellularized tissue was then enzymatically modified to be injectable and form a gel at 37°C. Following this, the mechanical properties, microstructure, cytotoxicity, and neuroinhibitory properties were analyzed. The decellularization process removed 99% of DNA and maintained 74% of sGAGs and 154% of collagen compared to the controls NPs. Rheology demonstrated that regelled NP exhibited properties similar to but slightly lower than collagen-matched controls. Culture of NP cells in the regelled NP demonstrated an increase in metabolic activity and DNA content over 7 days. The collagen content of the regelled NP stayed relatively constant over 7 days. Analysis of the neuroinhibitory properties demonstrated regelled NP significantly inhibited neuronal growth compared to collagen controls. The decellularization process developed here for porcine NP tissue was able to remove the antigenic material while maintaining the sGAG and collagen. This decellularized tissue was then able to be modified into a thermally forming gel that maintained the viability of cells and demonstrated robust neuroinhibitory properties in vitro. This biomaterial holds promise as an NP supplement to prevent nerve growth into the native disc and NP in vivo.

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Carbohydrate epitopes currently recognized as targets for IgE antibodies.

Platts-Mills TA, Hilger C, Jappe U, van Hage M, Gadermaier G, et al.

Allergy • 2021-Aug-01

Until recently, glycan epitopes have not been documented by the WHO/IUIS Allergen Nomenclature Sub-Committee. This was in part due to scarce or incomplete information on these oligosaccharides, but also due to the widely held opinion that IgE to these epitopes had little or no relevance to allergic symptoms. Most IgE-binding glycans recognized up to 2008 were considered to be "classical" cross-reactive carbohydrate determinants (CCD) that occur in insects, some helminths and throughout the plant kingdom. Since 2008, the prevailing opinion on lack of clinical relevance of IgE-binding glycans has been subject to a reevaluation. This was because IgE specific for the mammalian disaccharide galactose-alpha-1,3-galactose (alpha-gal) was identified as a cause of delayed anaphylaxis to mammalian meat in the United States, an observation that has been confirmed by allergists in many parts of the world. Several experimental studies have shown that oligosaccharides with one or more terminal alpha-gal epitopes can be attached as a hapten to many different mammalian proteins or lipids. The classical CCDs also behave like haptens since they can be expressed on proteins from multiple species. This is the explanation for extensive in vitro cross-reactivity related to CCDs. Because of these developments, the Allergen Nomenclature Sub-Committee recently decided to include glycans as potentially allergenic epitopes in an adjunct section of its website (www.allergen.org). In this article, the features of the main glycan groups known to be involved in IgE recognition are revisited, and their characteristic structural, functional, and clinical features are discussed.

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