Establishment of a protein biochip to detect serum IgG antibodies against IL-2 and soluble CD25 in hemophagocytic lymphohistiocytosis

Lei, Qian; Liu, Sheng‐Sheng; Li, Song-Guo; Gao, Yi; Ye, Lei; Johnson, Gabrielle Olivia Ramsay; Song, Zijian; Du, Wei‐Dong

doi:10.1016/j.cca.2018.10.008

Cited by 5 publications

(11 citation statements)

References 30 publications

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“…The ligand IL-2 molecule on the biochip specifically captures its receptor CD25, if any, in HLH serum. In this study, using the ligand/receptor-based biochip assays, on the one hand, we found that the positive rates of ligand IL-2 and receptor sCD25 monomers in the sera were 14.3% and 71.4%, respectively, which were in accordance with our previous α-IL-2 or α-sCD25antibodybased biochip investigation, in which ligand IL-2 and receptor sCD25 monomer in the HLH sera have been detected using their relevant specific antibodies [15]. Our data indicated that the biochip shared an impressive compatibility with CLIA assay in the measurement of sCD25.…”

Section: Discussionsupporting

confidence: 90%

“…In this study, the immunological detection efficacy on the biochips indicated that ligand IL-2-based CD25 assay revealed more sensitive than receptor CD25-based IL-2 assay (78 pg/mL vs.156 pg/mL). The LOD values were similar to those reported previously [12,15]. We supposed that molecular size of proteins as linkers on the biological surface would be attributable to the potentials.…”

Section: Discussionsupporting

confidence: 89%

“…The biochip technique in combination with a self-assembling monolayer offers a high-throughput platform and enables the detection of multiple proteins in the serum [12][13][14] Hemophagocytic lymphohistiocytosis (HLH), a rare but potentially life-threatening illness caused due to pathological activation of the immune system, is characterized by a classical and critical sign of "cytokine storm," which exhibits enhanced levels of IL-10, IL1β, IL-6, IL-8, TNF-α, IL-2, and soluble CD25 (sCD25) in the serum. Previously, we used a cytokine antibody-based biochip strategy, similar to an ELISA assay, to detect specific free or unbound cytokine monomers in the HLH serum [15]. IL-2 specifically recognizes sCD25, one of the three forms of IL-2 receptors.…”

Section: Introductionmentioning

confidence: 99%

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A simplified direct on-chip forward or reverse immune assay for understanding protein-protein interactions in the serum

Liu¹,

Ye²,

Li³

et al. 2022

Preprint

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Background: The identification of protein-protein interactions is of great challenge. Therefore, we conducted this study to fabricate a gold surface biochip with activated sophorolipids in combination with 16-amino-1-hexadecanethiol hydrochloride. Methods: We designed a direct on-chip immunological assay strategy for measuring ligand-receptor interactions in a forward or reverse manner, that is, a ligand was immobilized on the biochip surface and allowed to interact with its specific free receptor in the liquid phase and vice versa. The specificity of molecular interactions on the biochip was evaluated using an immunological blocking assay and a chemiluminescent immunoassay. To test the potential utilization of biochip, we used the serum of hemophagocytic lymphohistiocytosis (HLH) patients as an experimental entity. Results: The receptor CD25-based IL-2 and ligand IL-2-based CD25 assays revealed that the detection limits on the biochip were as low as 156pg/mL and 78pg/mL, respectively. Meanwhile, using the receptor- or ligand-based platforms, we found that the positive rates of free IL-2 and soluble CD25 (sCD25) monomers in the sera of HLH patients were 14.3% and 71.4%, respectively, like our previous specific-antibody-based biochip investigation. Also, the biochip shared a good compatibility with CLIA assay in the measurement of sCD25(r=0.77, P<0.01). Conclusions: The biochip platform can be expanded to protein-specific serological diagnosis as a potential substitute for immunoprecipitation and ELISA to understand the interactions between proteins, ligands and receptors, and enzymes and substrates.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

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A simplified direct on-chip forward or reverse immune assay for understanding protein-protein interactions in the serum

Liu¹,

Ye²,

Li³

et al. 2022

Preprint

Self Cite

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“…LD, also known as short linear glucan, short-chain amylose, and short maltodextrin, is produced when amylopectin is hydrolyzed by pullulanase or isoamylase [ 6 , 7 , 8 , 9 , 10 ]. LD has wide applications in the food and pharmaceutical industries, such as starch nanoparticles [ 11 , 12 ], inclusion complexes [ 13 , 14 ], and hydrogels [ 15 ]. LD shows high biocompatibility and biodegradability [ 16 , 17 ], which gives LD-based inclusion the optimal DP values of LD for encapsulating insulin, making it an ideal carrier system with applications in different fields, including food, cosmetics, pharmaceuticals, and tissue engineering [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Linear Dextrin as Potential Insulin Delivery System: Effect of Degree of Polymerization on the Physicochemical Properties of Linear Dextrin–Insulin Inclusion Complexes

Xie

Wang

et al. 2021

Polymers

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In the current study, linear dextrin (LD) was prepared using waxy potato starch debranched with pullulanase, which has attracted immense interest in the food, pharmaceutical, and cosmetic industries as a versatile ingredient. Various LDs were separated on the basis of their differential solubility in aqueous/ethanol solutions of different volumetric ratios. Three LD products—LD Fabrications with 40% ethanol (F-40); LD Fabrications with 50% ethanol (F-50); and LD Fabrications with 60%, 70%, and 80% ethanol (F-M)—were obtained with an average degree of polymerization (DP) values of 31.44, 21.84, and 16.10, respectively. The results of Fourier transform infrared spectroscopy (FT-IR) analysis revealed that the reaction mainly involved hydrogen bonding and a hydrophobic interaction between LD and insulin in the process of inclusion complex formation. X-ray diffraction (XRD) results indicated that insulin was encapsulated in LD. The results of circular dichroism (CD) showed that the changes in the secondary structure of insulin were negligible during the release from the inclusion complexes. The order of encapsulation capacity is as follows: the complex composed of F-M and insulin (F-M-INS) > the complex composed of LD and insulin (LD-INS) > the complex composed of F-50 and insulin (F-50-INS) > and the complex composed of F-40 and insulin (F-40-INS). F-M-INS inclusion complexes showed a better effect on reducing the release of insulin in gastric juice and promoting the release of insulin in intestinal juice and blood plasma than LD-INS.

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“…it has previously been demonstrated in mouse models that neutralizing anti-iFn-γ antibody (ab) may be an effective therapy for HlH (10,11). However, only a few studies have investigated anti-cytokine antibodies produced by patients with HlH (12,13).…”

Section: Introductionmentioning

confidence: 99%

Development of a dendrimer PAMAM‑based gold biochip for rapid and sensitive detection of endogenous IFN‑γ and anti‑IFN‑γ IgG in patients with hemophagocytic lymphohistiocytosis

Song

et al. 2020

Mol Med Rep

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Hemophagocytic lymphohistiocytosis (HlH) is a rare but severe disease characterized by immune hyperactivation and cytokine storm. Given the high mortality rate of HlH, there is a need for more effective diagnostic tools and treatments. The present study developed a dendrimer-based protein biochip for rapid, sensitive and simultaneous detection of serum interferon (iFn)-γ and endogenous anti-iFn-γ antibody (ab) in patients with HlH. a gold biochip was modified with 1, 4-phenylene diisothiocyanate (PdiTc), polyamidoamine (PaMaM) or PdiTc-activated PaMaM. The optimal immobilization concentration for ab capture and the reaction concentration for detecting ab on the PDITC-activated PAMAM-modified biochip were 6.25 and 3.12 µg/ml, respectively; the limit of detection of iFn-γ protein was 50 pg/ml. The efficiency of the protein-probed biochip in detecting iFn-γ and anti-iFn-γ ab in serum samples from 77 patients with HlH was evaluated; the positive rates for iFn-γ and anti-iFn-γ igG ab were 63.6% (49/77) and 61.0% (47/77), respectively. The present results demonstrated that the PDITC-activated PAMAM-modified biochip might be a sensitive tool for the specific detection of iFn-γ and anti-iFn-γ ab in serum, and might have clinical applicability for the diagnosis of HlH.

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Establishment of a protein biochip to detect serum IgG antibodies against IL-2 and soluble CD25 in hemophagocytic lymphohistiocytosis

Cited by 5 publications

References 30 publications

A simplified direct on-chip forward or reverse immune assay for understanding protein-protein interactions in the serum

A simplified direct on-chip forward or reverse immune assay for understanding protein-protein interactions in the serum

Linear Dextrin as Potential Insulin Delivery System: Effect of Degree of Polymerization on the Physicochemical Properties of Linear Dextrin–Insulin Inclusion Complexes

Development of a dendrimer PAMAM‑based gold biochip for rapid and sensitive detection of endogenous IFN‑γ and anti‑IFN‑γ IgG in patients with hemophagocytic lymphohistiocytosis

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