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Immunology of Allergic Diseases
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
The pathway to better preventive and therapeutic strategies for allergic diseases lies in the careful dissection of the atopic march, the immunological basis of the allergic inflammation in the context of genetic, epigenetic factors as well as environmental factors. Further elucidation of the mechanisms and pathways of allergic inflammation will be facilitated by the ‘omics’ era when, functional genomics, immunogenomics, immunoproteomics are integrated with nutritional genomics and pharmacogenomics in the context of translational research focused on individual and community health.
Grass pollen allergens
Published in Richard F. Lockey, Dennis K. Ledford, Allergens and Allergen Immunotherapy, 2020
Novel IgE-binding proteins localized to the pollen extracellular coat matrix are present in Bermuda grass pollen using an immunoproteomics approach. A cysteine protease (23 kDa) and an endoxylanase (30 kDa) were recovered from pollen grains by cyclohexane extraction, separated electrophoretically, and analyzed by IgE immunoblotting and proteomics [140]. A significant percentage (25%–57%) of grass pollen allergic subjects possess IgE reactivity toward these two proteins, suggesting that they may be clinically important Bermuda grass pollen allergens. Peptide sequencing of IgE-reactive bands from pollen coat fractions derived from timothy grass and Johnson grass pollen confirm the presence of homologous cysteine proteases. Additionally, the purified cysteine protease induces epithelial cell detachment and disruption of the integrity of airway epithelial cells.
The role of proteomics in defining autoimmunity
Published in Expert Review of Proteomics, 2021
Starting from 2000, immunoproteomics is yielding a comprehensive wider and deeper comprehension of immune diseases and of their progression by identifying and quantifying protein and peptide biomarkers to be used in diagnostics and able to predict clinical response. Notably, immunoproteomics is also providing clinical answers to the immunological issue of immunogenicity vs. autoimmunity. In fact, evoking an immune defensive response exempt of pathologic autoimmune cross-reactions is a main issue of current immunotherapies. In this regard, immunoproteomics and comparative proteomics are making available the methodologies and the data for scientifically defining immunogenicity and autoimmunity, therefore introducing the principle of sequence uniqueness as a rationale to develop peptides able to specifically block autoantibodies in autoimmune diseases and, as well, to formulate immunotherapies capable of specifically hitting tumor-associated antigens and pathogens in cancer and infectious diseases. Then, it is also worth noting the possibility of expanding immunotherapeutical approaches to peptide targets of autoantibodies that are post-translationally modified by (a)symmetrical methylation, citrullination, carbamoylation, glycation, et alia.
Proteomics in support of immunotherapy: contribution to model-based precision medicine
Published in Expert Review of Proteomics, 2022
Emmanuel Nony, Philippe Moingeon
Proteomics has been most particularly useful to build up host pathogen interaction networks in the form of protein–protein interactomes [67,68]. It also allowed to identify virulence factors and understand how pathogens could affect the host cell proteome. For example, certain virulence factors lead to the ubiquitination or SUMOylation of host cell proteins, which program them to subsequent degradation [67]. Proteomics is being used as well to characterize both pharmaceutical grade monoclonal antibodies, as well antigens incorporated into vaccines. Proteins most relevant in this latter application to elicit protective immune responses include viral envelope proteins and bacterial surface receptors involved in host cell infection, as well as virulence factors predicted based upon amino-acid sequence or structural homologies with known toxins. All these applications require a deep characterization of potential isoforms and glycoforms of those proteins of therapeutic interest, as they may display distinct functional repertoires and immunogenicity profiles. Proteomics also encompasses the identification of immune epitopes within a candidate antigen recognized by either CD8+ or CD4 + T lymphocytes or neutralizing antibodies [66,67]. In vaccinology, immunoproteomics is further implemented to characterize natural protective immune responses, with an interest in documenting innate and adaptive immune responses occurring in the blood or at mucosal surfaces of patients protected against the pathogen, in comparison with those who lack protective immunity [67]. These studies can yield BMKs useful to monitor immune responses in patients during pre and/ or post-vaccination.
Proteomics approach to understand bacterial antibiotic resistance strategies
Published in Expert Review of Proteomics, 2019
Bo Peng, Hui Li, Xuanxian Peng
In clinically isolated multidrug-resistant Escherichia coli strain C999, the whole-cell proteome, and the membrane, cytoplasmic, periplasmic and extracellular sub-proteomes show that the differential abundance of proteins are related to stress responses, cellular responses, and antibiotic and drug responses, consistent with multidrug-resistance phenotypes [16]. The proteomes of four multidrug-resistant E. coli strains with different genetic profiles show an identical alteration in transporters, stress responses, or metabolic proteins [34]. LC-MS/MS-based proteomics and qRT-PCR are used to quantify total envelope proteins in the clinical relevance of an OqxR loss-of-function mutation, particularly in the context of beta-lactam susceptibility. The loss of OqxR specifically activates OqxAB efflux pump production >10,000-fold, whereas the absence of RamR activates AcrAB efflux pump production by about 5-fold. The former reduces β-lactam susceptibility and the later reduces fluoroquinolone susceptibility, but had little impact on β-lactam susceptibility even in the presence of β-lactamase [75]. The proteome profiles of multidrug-resistant and susceptible clinical isolates of E. coli and K. pneumoniae were compared to identify possible biological processes associated with drug resistant and susceptible phenotypes, respectively. An immunoproteomics approach was also used to identify immunoreactive proteins in these isolates. Translational machinery and catalytic activity are upregulated in multidrug-resistant E. coli and K. pneumoniae, respectively. The processes related to amino acid activation and tRNA amino-acylation are downregulated in the two multidrug-resistant strains, while higher immunoreactivity is detected in these multidrug-resistant strains compared to the susceptible strains [76]. Wang et al., used a proteomic approach to explore antibiotic resistance in three Acinetobacter baumannii isolates, a resistant isolate (A1), a less resistant isolate (A8), and a susceptible isolate (A9). The increased expression of I6TUC8, Q0GA83, 005286, and DOCCK1 may be responsible for higher resistance to ceftriaxone and gentamicin, respectively, in the A1 and A8 isolates compared to the A9 isolate. Higher expression levels of Q2FCY1, for stronger gentamicin resistance, and higher expression levels of L9LWL7, L9MDBO, K9C9W3, E2IGU7, B6E129, G8HYR7, D2XTBO, and D2XTBO, for stronger carbapenem resistance, are detected in the A1 isolate compared to the A8 isolate, respectively [77]. These results indicate that a proteomics approach can be used to provide a global view of clinical multidrug resistance and identify key proteins as biomarkers.