Proteomic approach to profiling immune complex antigens in cerebrospinal fluid samples from patients with central nervous system autoimmune diseases

Aibara, Nozomi; Ichinose, Kunihiro; Baba, Miyako; Nakajima, Hideki; Satoh, Katsuya; Atarashi, Ryuichiro; Kishikawa, Naoya; Nishida, Naoshi; Kawakami, Atsushi; Kuroda, Naotaka; Ohyama, Kaname

doi:10.1016/j.cca.2018.05.026

Cited by 20 publications

(11 citation statements)

References 52 publications

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“…However, in the present study, this analysis was modified to evaluate the ICs in other fluid samples. In fact, we identified disease-specific IC-antigen from cerebrospinal fluid in patients with central nervous system autoimmune diseases and from follicular fluid in infertile patients (19,20). One of most important results in the present study is that IC-ceruloplasmin was the most useful BC-related urine marker because its positive rate in BC was higher than that in all non- tumoral conditions and was also significantly associated with grade, T stage, invasive potential, and urinary tract recurrence.…”

Section: Discussionmentioning

confidence: 52%

Detection of Novel Urine Markers Using Immune Complexome Analysis in Bladder Cancer Patients: A Preliminary Study

Aibara

Miyata

Araki

et al. 2021

In Vivo

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Background/Aim: Little is known on urine biomarkers that are associated with malignant behavior in patients with bladder cancer (BC). Our aim was to identify BC-related factors in urine samples using our original method "immune complexome analysis", based on detecting the immune complex (IC). Patients and Methods: Immune complexome analysis was performed using urine samples from 97 BC patients, including 67 with non-muscle invasive BC (NMIBC). Results: Eight IC-antigens were recognized as candidates for BC-related factors from 20,165 proteins. ICserum albumin, -fibrinogen γ chain, -hemoglobin subunit α, -hemoglobin subunit β, -ceruloplasmin, and fibrinogen β chain were significantly associated with either pathological features and/or outcome. IC-ceruloplasmin was most widely associated with pathological features in all BC patients and lamina propria invasion and urinary tract recurrence in NMIBC. Conclusion: Based on detection of IC-antigens it was demonstrated that six IC-antigens, especially ICceruloplasmin, are potential urine biomarkers in BC.

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Section: Discussionmentioning

confidence: 52%

Detection of Novel Urine Markers Using Immune Complexome Analysis in Bladder Cancer Patients: A Preliminary Study

Aibara

Miyata

Araki

et al. 2021

In Vivo

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“…We previously developed an ‘immune complexome analysis’ capable of identifying specific antigens in ICs in biological fluids. The method uses IC‐capturing beads and nano‐liquid chromatography–tandem mass spectrometry (nano‐LC‐MS/MS) to comprehensively identify and profile IC‐antigens [19–23]. To confirm the presence of ICs formed by AMA‐antigens in PBC sera, we analyzed sera from patients with PBC as well as four other typical autoimmune diseases (SS, SLE, RA and SSc) using immune complexome analysis.…”

Section: Introductionmentioning

confidence: 99%

Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients

Aibara

Ohyama

Nakamura

et al. 2021

Clinical and Experimental Immunology

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Summary Primary biliary cholangitis (PBC) is characterized by the presence of serum anti‐mitochondrial autoantibodies (AMAs). To date, four antigens among the 2‐oxo‐acid dehydrogenase complex family, which commonly have lipoyl domains as an epitope, have been identified as AMA‐corresponding antigens (AMA‐antigens). It has recently been reported that AMAs react more strongly with certain chemically modified mimics than with the native lipoyl domains in AMA‐antigens. Moreover, high concentrations of circulating immune complexes (ICs) in PBC patients have been reported. However, the existence of ICs formed by AMAs and their antigens has not been reported to date. We hypothesized that AMAs and their antigens formed ICs in PBC sera, and analyzed sera of PBC and four autoimmune diseases (Sjögren's syndrome, systemic lupus erythematosus, systemic scleroderma, and rheumatoid arthritis) using immune complexome analysis, in which ICs are separated from serum and are identified by nano‐liquid chromatography‐tandem mass spectrometry. To correctly assign MS/MS spectra to peptide sequences, we used a protein‐search algorithm that including lipoylation and certain xenobiotic modifications. We found three AMA‐antigens, the E2 subunit of the pyruvate dehydrogenase complex (PDC‐E2), the E2 subunit of the 2‐oxo‐glutarate dehydrogenase complex (OGDC‐E2) and dihydrolipoamide dehydrogenase binding protein (E3BP), by detecting peptides containing lipoylation and xenobiotic modifications from PBC sera. Although the lipoylated sites of these peptides were different from the well‐known sites, abnormal lipoylation and xenobiotic modification may lead to production of AMAs and the formation ICs. Further investigation of the lipoylated sites, xenobiotic modifications, and IC formation will lead to deepen our understanding of PBC pathogenesis.

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“…We have developed an 'immune complexome analysis' method to comprehensively identify the antigens in ICs using IC-capturing beads and nano-liquid chromatographytandem mass spectrometry (nano-LC-MS/MS) [9]. Using this method, we have analyzed biological fluids (serum, cerebrospinal fluids) of patients with several autoimmune diseases [10][11][12][13][14] (e.g. rheumatoid arthritis and systemic lupus erythematosus), cancers [15] (e.g.…”

Section: Introductionmentioning

confidence: 99%

Immune complexome analysis reveals the presence of immune complexes and identifies disease-specific immune complex antigens in saliva samples from patients with Sjögren's syndrome

Yamane

Nakamura

Hamasaki

et al. 2021

Clinical and Experimental Immunology

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Sjögren's syndrome (SS) is a chronic autoimmune disease that mainly damages the salivary and lacrimal glands. Immune complex (IC) formation triggers local inflammation through IC deposition and decreased antigen function. Some ICs can leak from the lesion and into the saliva, but no salivary ICs have been reported to date. We used immune complexome analysis to comprehensively identify antigens incorporated into IC (IC-antigens) in saliva samples from patients with SS (n = 9) or with xerostomia (n = 7). Neutrophil defensin 1 (67%), small proline-rich protein 2D (67%), myeloperoxidase (44%), neutrophil elastase (44%), cathepsin G (33%), nuclear mitotic apparatus 1 (33%) and phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma (33%) were identified as new IC-antigens specifically and frequently detected in the saliva of SS patients. Of these, neutrophil defensin 1, myeloperoxidase, neutrophil elastase and cathepsin G are neutrophil intracellular proteins, which suggests that repeated destruction of neutrophils due to abnormal autoimmunity may be involved in the pathogenesis of SS. We also analyzed serum samples from three SS patients. There was little overlap of ICantigens between two of the samples (fewer than 30% of the IC-antigens in the saliva samples), suggesting that many ICs are formed locally and independently of the circulation. In addition, we found that four SS-specific salivary antigens show sequence homology with several proteins of oral microbiomes but no antigen has homology with Epstein-Barr virus proteins. The homology between some IC-antigens and oral microbiome proteins may indicate the impact of oral infection on local autoimmunity through molecular mimicry theory.

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Proteomic approach to profiling immune complex antigens in cerebrospinal fluid samples from patients with central nervous system autoimmune diseases

Cited by 20 publications

References 52 publications

Detection of Novel Urine Markers Using Immune Complexome Analysis in Bladder Cancer Patients: A Preliminary Study

Detection of Novel Urine Markers Using Immune Complexome Analysis in Bladder Cancer Patients: A Preliminary Study

Investigation of immune complexes formed by mitochondrial antigens containing a new lipoylated site in sera of primary biliary cholangitis patients

Immune complexome analysis reveals the presence of immune complexes and identifies disease-specific immune complex antigens in saliva samples from patients with Sjögren's syndrome

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