Albumin obscures sex differences in blood protein patterns of rats and humans

Gersten, Douglas M.; Khirabadi, Bijan S.; Kurian, Pawels; Ledley, Robert S.; Mahany, T M; Ramey, Estelle R.; Ramwell, Peter W.

doi:10.1042/bj1910869

Cited by 9 publications

(5 citation statements)

References 11 publications

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“…An increased number of differentially-expressed proteins was identified in depleted sera samples, compared with non-depleted sera samples (163 vs. 117, respectively). This is not unexpected, due to the major plasma proteins (albumin and Igs) being known to mask detection of minor plasma proteins (25). Unexpectedly, the proteins whose levels of expression markedly differed between T2DM and control samples has an increased number in the non-depleted sera samples, compared with the depleted sera samples.…”

Section: Discussionmentioning

confidence: 97%

LC‑MS/MS proteomic analysis revealed novel associations of 37 proteins with T2DM and notable upregulation of immunoglobulins

et al. 2019

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Type 2 diabetes mellitus (T2DM) is a disease associated with a number of metabolic disturbances, including protein metabolism. In the present study, blood samples were obtained from Bahraini subjects, including 6 patients with T2DM and 6 age- and sex-matched, non-diabetic, healthy controls. Depleted and non-depleted sera were prepared from the collected blood, and the global protein expression changes were evaluated by liquid chromatography tandem mass spectrometry. Only significantly and markedly differentially-expressed proteins (P<0.05, analysis of variance; maximum fold change ≥1.5) were considered as candidate proteins for informatics analysis. Accordingly, a total of 62 proteins were identified to be differentially expressed in T2DM, compared with control subjects, and they were grouped functionally into 16 classes of proteins. The largest class was that of the immune-associated proteins. Additionally, ~25 of these proteins (40%) had previously been associated with DM; however, the association of the other 37 proteins with T2DM was a novel observation. The majority of the identified proteins were upregulated in T2DM. The identified proteins could be involved in the pathogenesis of the disease or serve as disease biomarkers. Further validation of the identified proteins in a large study cohort is required, in order to fully access their potential clinical usefulness.

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Section: Discussionmentioning

confidence: 97%

LC‑MS/MS proteomic analysis revealed novel associations of 37 proteins with T2DM and notable upregulation of immunoglobulins

et al. 2019

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“…HD phenotypic measures have previously been shown to have complex relationships with sex [ 36 ]. However it is also possible that our findings are due to haemodynamic differences between males and females [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Quantification of huntingtin protein species in Huntington’s disease patient leukocytes using optimised electrochemiluminescence immunoassays

et al. 2017

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BackgroundHuntington’s disease (HD) is an autosomal dominant neurodegenerative condition caused by an expanded CAG repeat in the gene encoding huntingtin (HTT). Optimizing peripheral quantification of huntingtin throughout the course of HD is valuable not only to illuminate the natural history and pathogenesis of disease, but also to detect peripheral effects of drugs in clinical trial.RationaleWe previously demonstrated that mutant HTT (mHTT) was significantly elevated in purified HD patient leukocytes compared with controls and that these levels track disease progression. Our present study investigates whether the same result can be achieved with a simpler and more scalable collection technique that is more suitable for clinical trials.MethodsWe collected whole blood at 133 patient visits in two sample sets and generated peripheral blood mononuclear cells (PBMCs). Levels of mHTT, as well as N-, and C-terminal and mid-region huntingtin were measured in the PBMCs using ELISA-based Meso Scale Discovery (MSD) electrochemiluminescence immunoassay platforms, and we evaluated the relationship between different HTT species, disease stage, and brain atrophy on magnetic resonance imaging.ConclusionsThe assays were sensitive and accurate. We confirm our previous findings that mHTT increases with advancing disease stage in patient PBMCs, this time using a simple collection protocol and scalable assay.

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“…High abundant proteins have been shown to be responsible for concealing putative markers. For example, albumin was found to obscure sex differences in blood plasma of rats and humans [2]. A failure to effectively remove high abundant proteins can also result in failed or incomplete biomarker studies.…”

Section: Discussionmentioning

confidence: 99%

“…For example, twenty-two proteins comprise over 90% of the total protein mass in human serum and albumin alone accounts for over 50%. These dominant species prevent the detection of lower-abundance proteins that may be of greater interest as putative biomarkers [2]. Therefore, a successful system of proteomic sample preparation to remove these high abundant proteins is needed to examine lower abundant proteins of interest and to reduce the complexity for improved biomarker discovery.…”

Section: Introductionmentioning

confidence: 99%

High abundant protein removal from rodent blood for biomarker discovery

Haudenschild

Eldridge

Lein

et al. 2014

Biochemical and Biophysical Research Communications

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In order to realize the goal of stratified and/or personalized medicine in the clinic, significant advances in the field of biomarker discovery are necessary. Adding to the abundance of nucleic acid biomarkers being characterized, additional protein biomarkers will be needed to satisfy diverse clinical needs. An appropriate source for finding these biomarkers is within blood, as it contains tissue leakage factors as well as additional proteins that reside in blood that can be linked to the presence of disease. Unfortunately, high abundant proteins and complexity of the blood proteome present significant challenges for the discovery of protein biomarkers from blood. Animal models often enable the discovery of biomarkers that can later be translated to humans. Therefore, determining appropriate sample preparation of proteomic samples in rodent models is an important research goal. Here, we examined both mouse and rat blood samples (including both serum and plasma), for appropriate high abundant protein removal techniques for subsequent gel-based proteomic experiments. We assessed four methods of albumin removal: antibody-based affinity chromatography (MARS), Cibacron® Blue-based affinity depletion (SwellGel® Blue Albumin Removal Kit), protein-based affinity depletion (ProteaPrep Albumin Depletion Kit) and TCA/acetone precipitation. Albumin removal was quantified for each method and SDS-PAGE and 2-DE gels were used to quantify the number of protein spots obtained following albumin removal. Our results suggest that while all four approaches can effectively remove high abundant proteins, antibody-based affinity chromatography is superior to the other three methods.

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Albumin obscures sex differences in blood protein patterns of rats and humans

Cited by 9 publications

References 11 publications

LC‑MS/MS proteomic analysis revealed novel associations of 37 proteins with T2DM and notable upregulation of immunoglobulins

LC‑MS/MS proteomic analysis revealed novel associations of 37 proteins with T2DM and notable upregulation of immunoglobulins

Quantification of huntingtin protein species in Huntington’s disease patient leukocytes using optimised electrochemiluminescence immunoassays

High abundant protein removal from rodent blood for biomarker discovery

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