Is isolation of comprehensive human plasma peptidomes an achievable quest?

Mahboob, Sadia; Mohamedali, Abidali; Ahn, Seong Beom; Schulz‐Knappe, Peter; Nice, Edouard C.; Baker, Mark S.

doi:10.1016/j.jprot.2015.05.010

Cited by 34 publications

(30 citation statements)

References 114 publications

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“…Because there are few free peptides in blood (57), it was logically to suggest their local generation. Because there are no active inflammation processes in the CNS, these peptides must have been the result of the abovementioned local inflammation in the DRGs and dorsal roots.…”

Section: Discussionmentioning

confidence: 99%

The Pathogenesis of the Demyelinating Form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and Immunological Profiling of Physiological Fluids

Ziganshin

Ivanova

Lomakin

et al. 2016

Molecular & Cellular Proteomics

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Acute inflammatory demyelinating polyneuropathy (AIDP) -the main form of Guillain-Barre syndrome-is a rare and severe disorder of the peripheral nervous system with an unknown etiology. One of the hallmarks of the AIDP pathogenesis is a significantly elevated cerebrospinal fluid (CSF) protein level. In this paper CSF peptidome and proteome in AIDP were analyzed and compared with multiple sclerosis and control patients. A total protein concentration increase was shown to be because of even changes in all proteins rather than some specific response, supporting the hypothesis of protein leakage from blood through the blood-nerve barrier. The elevated CSF protein level in AIDP was complemented by activization of protein degradation and much higher peptidome diversity. Because of the studies of the acute motor axonal form, Guillain-Barre syndrome as a whole is thought to be associated with autoimmune response against neurospecific molecules. Thus, in AIDP, autoantibodies against cell adhesion proteins localized at Ranvier's nodes were suggested as possible targets in AIDP. Indeed, AIDP CSF peptidome analysis revealed cell adhesion proteins degradation, however no reliable dependence on the corresponding autoantibodies levels was found. Proteome analysis revealed overrepresentation of Gene Ontology groups related to responses to bacteria and virus infections, which were earlier suggested as possible AIDP triggers. Immunoglobulin blood serum analysis against most common neuronal viruses did not reveal any specific pathogen; however, AIDP patients were more immunopositive in average and often had polyinfections. Cytokine analysis of both AIDP CSF and blood did not show a systemic adaptive immune response or general inflammation, whereas innate immunity cytokines were up-regulated. To supplement the widely-accepted though still unproven autoimmunity-based AIDP mechanism we propose a hypothesis of the primary peripheral nervous system damaging initiated as an innate immunity-associated local inflammation following neurotropic viruses egress, whereas the autoantibody production might be an optional complementary secondary process. Molecular & Cellular

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Section: Discussionmentioning

confidence: 99%

The Pathogenesis of the Demyelinating Form of Guillain-Barre Syndrome (GBS): Proteo-peptidomic and Immunological Profiling of Physiological Fluids

Ziganshin

Ivanova

Lomakin

et al. 2016

Molecular & Cellular Proteomics

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“…Peptidomics has been defined as the comprehensive, qualitative, and quantitative study of all native peptides in a tissue or biofluid [ 2 ]. To set a boundary, peptides are mostly defined as low molecular weight compounds (< 10 kDa) [ 3 , 4 ]. Markedly, these peptides are associated with the proteome of the biofluids from which they originate.…”

Section: Introductionmentioning

confidence: 99%

“…They are mostly derived by specific proteases and can be further modified by post-translational modifications (PTMs). Because of their size, endogenous peptides are found throughout the body, in both the intercellular and extracellular spaces, and potentially have unrestricted vascular and interstitial access [ 3 ]. Because of these characteristics, the peptidome has become of interest as a diagnostic tool for biomarker discovery for specific disease states [ 3 – 7 ].…”

Section: Introductionmentioning

confidence: 99%

Toward an efficient workflow for the analysis of the human milk peptidome

et al. 2019

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There is a growing interest for investigating endogenous peptides from human biofluids which may provide yet unknown functional benefits or provide an early indication of disease states as potential biomarkers. A major technical bottleneck in the investigation of endogenous peptides from body fluids, e.g., serum, urine, saliva, and milk, is that each of these fluids seems to require unique workflows for peptide extraction and analysis. Thus, protocols optimized for serum cannot be directly translated to milk. One biofluid that is readily available, but which has not been extensively explored, is human milk, whose analysis could contribute to our understanding of the immune development of the newborn infant. Due to the occurrence of highly abundant lipids, proteins, and saccharides, milk peptidomics requires dedicated sample preparation steps. The aim of this study was to develop a time and cost-efficient workflow for the analysis of the human milk peptidome, for which we compared peptide extraction methodologies and peptide fragmentation methods. A method using strong acid protein precipitation and analysis by collision-induced dissociation fragmentation was found to be superior to all other test methods, allowing us qualitative and quantitative detection of about 4000 endogenous human milk peptides in a total analysis time of just 18 h. Electronic supplementary material The online version of this article (10.1007/s00216-018-01566-4) contains supplementary material, which is available to authorized users.

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“…The fact that polypeptides this small breach the blood–brain barrier, tumors, the vascular system, and interstitial space make them of interest as both therapeutic agents and biomarkers. 66 Their size and abundance enable a series of purification methods that differentiate them from proteins. Among the methods most widely used are (i) size fraction methods, (ii) organic solvent extraction, 67 and (iii) immunoaffinity based abundant protein removal.…”

Section: Fractionation Of Structurally Similar Proteinsmentioning

confidence: 99%