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Published in: Journal of Clinical Immunology 2/2020

01-02-2020 | Immunodeficiency | Original Article

RP-HPLC-ESI-IT Mass Spectrometry Reveals Significant Variations of the Human Salivary Protein Profile Associated with Predominantly Antibody Deficiencies

Authors: Cristina Contini, Davide Firinu, Simone Serrao, Barbara Manconi, Alessandra Olianas, Francesco Cinetto, Fausto Cossu, Massimo Castagnola, Irene Messana, Stefano Del Giacco, Tiziana Cabras

Published in: Journal of Clinical Immunology | Issue 2/2020

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Abstract

Purpose

Present study is designed to discover potential salivary biomarkers associated with predominantly antibody deficiencies, which include a large spectrum of disorders sharing failure of antibody production, and B cell defects resulting in recurrent infections, autoimmune and inflammatory manifestations, and tumor susceptibility. Understanding and clinical classification of these syndromes is still challenging.

Methods

We carried out a study of human saliva based on liquid chromatography-mass spectrometry measurements of intact protein mass values. Salivary protein profiles of patients (n = 23) and healthy controls (n = 30) were compared.

Results

Patients exhibited lower abundance of α-defensins 1-4, cystatins S1 and S2, and higher abundance of glutathionylated cystatin B and cystatin SN than controls. Patients could be clustered in two groups on the basis of different levels of cystatin SN, S1 and S2, suggesting that these proteins may play different roles in the disease.

Conclusions

Quantitative variations of these pro-inflammatory and antimicrobial peptides/proteins may be related to immunodeficiency and infectious condition of the patients. The high incidence of tumors in the group with the highest level of cystatin SN, which is recognized as tumoral marker, appeared an intriguing result deserving of future investigations. Data are available via ProteomeXchange with identifier PXD012688.
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Literature
1.
go back to reference Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38:129–43.PubMed Bousfiha A, Jeddane L, Picard C, Ailal F, Bobby Gaspar H, Al-Herz W, et al. The 2017 IUIS phenotypic classification for primary immunodeficiencies. J Clin Immunol. 2018;38:129–43.PubMed
2.
go back to reference Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International consensus document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4:38–59.PubMed Bonilla FA, Barlan I, Chapel H, Costa-Carvalho BT, Cunningham-Rundles C, de la Morena MT, et al. International consensus document (ICON): common variable immunodeficiency disorders. J Allergy Clin Immunol Pract. 2016;4:38–59.PubMed
3.
go back to reference Kienzler AK, Hargreaves CE, Patel SY. The role of genomics in common variable immunodeficiency disorders. Clin Exp Immunol. 2017;188:326–32.PubMed Kienzler AK, Hargreaves CE, Patel SY. The role of genomics in common variable immunodeficiency disorders. Clin Exp Immunol. 2017;188:326–32.PubMed
4.
go back to reference Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112:277–86.PubMed Chapel H, Lucas M, Lee M, Bjorkander J, Webster D, Grimbacher B, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112:277–86.PubMed
5.
go back to reference Patuzzo G, Barbieri A, Tinazzi E, Veneri D, Argentino G, Moretta F, et al. Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimm Rev. 2016;15:877–82. Patuzzo G, Barbieri A, Tinazzi E, Veneri D, Argentino G, Moretta F, et al. Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimm Rev. 2016;15:877–82.
6.
go back to reference Cunningham-Rundles C. The many faces of common variable immunodeficiency. Hematology Am Soc Hematol Educ Program. 2012;2012:301–5.PubMed Cunningham-Rundles C. The many faces of common variable immunodeficiency. Hematology Am Soc Hematol Educ Program. 2012;2012:301–5.PubMed
7.
go back to reference Knight AK, Cunningham-Rundles C. Inflammatory and autoimmune complications of common variable immune deficiency. Autoimmun Rev. 2006;5:156–9.PubMed Knight AK, Cunningham-Rundles C. Inflammatory and autoimmune complications of common variable immune deficiency. Autoimmun Rev. 2006;5:156–9.PubMed
8.
go back to reference Boldovin S, Montin D, Martino S, Sciascia S, Menegatti E, Roccatello D. Common variable immunodeficiency: crossroads between infections, inflammation and autoimmunity. Autoimmun Rev. 2013;12:796–801. Boldovin S, Montin D, Martino S, Sciascia S, Menegatti E, Roccatello D. Common variable immunodeficiency: crossroads between infections, inflammation and autoimmunity. Autoimmun Rev. 2013;12:796–801.
9.
go back to reference Mortaz E, Tabarsi P, Mansouri D, Khosravi A, Garssen J, Velayati A, et al. Cancers related to immunodeficiencies: update and perspectives. Front Immunol. 2016;7:365.PubMedPubMedCentral Mortaz E, Tabarsi P, Mansouri D, Khosravi A, Garssen J, Velayati A, et al. Cancers related to immunodeficiencies: update and perspectives. Front Immunol. 2016;7:365.PubMedPubMedCentral
10.
go back to reference Bateman EA, Ayers L, Sadler R, Lucas M, Roberts C, Woods A, et al. T cell phenotypes in patients, with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections. Clin Exp Immunol. 2012;170:202–11.PubMedPubMedCentral Bateman EA, Ayers L, Sadler R, Lucas M, Roberts C, Woods A, et al. T cell phenotypes in patients, with common variable immunodeficiency disorders: associations with clinical phenotypes in comparison with other groups with recurrent infections. Clin Exp Immunol. 2012;170:202–11.PubMedPubMedCentral
11.
go back to reference Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Galicier L, Lepelletier Y, Webster D, et al. Common variable immunodeficiency is associated with defective functions of dendritic cells. Blood. 2004;104:2441–3.PubMed Bayry J, Lacroix-Desmazes S, Kazatchkine MD, Galicier L, Lepelletier Y, Webster D, et al. Common variable immunodeficiency is associated with defective functions of dendritic cells. Blood. 2004;104:2441–3.PubMed
12.
go back to reference Casulli S, Coignard-Biehler H, Amazzough K, Shoai-Tehrani M, Bayry J, Mahlaoui N, et al. Defective functions of polymorphonuclear neutrophils in patients with common variable immunodeficiency. Immunol Res. 2014;60:69–76.PubMed Casulli S, Coignard-Biehler H, Amazzough K, Shoai-Tehrani M, Bayry J, Mahlaoui N, et al. Defective functions of polymorphonuclear neutrophils in patients with common variable immunodeficiency. Immunol Res. 2014;60:69–76.PubMed
13.
go back to reference Carvalho KI, Melo KM, Bruno FR, Snyder-Cappione JE, Nixon DF, Costa-Carvalho BT, et al. Skewed distribution of circulating activated natural killer T (NKT) cells in patients with common variable immunodeficiency disorders (CVID). PLoS One. 2010;5:e1652. Carvalho KI, Melo KM, Bruno FR, Snyder-Cappione JE, Nixon DF, Costa-Carvalho BT, et al. Skewed distribution of circulating activated natural killer T (NKT) cells in patients with common variable immunodeficiency disorders (CVID). PLoS One. 2010;5:e1652.
14.
go back to reference Maggadottir SM, Li J, Glessner JT, Li YR, Wei Z, Chang X, et al. Rare variants at 16p11.2 are associated with common variable immunodeficiency. J. Allergy Clin. Immunol. 2015;135:1569–77.PubMedPubMedCentral Maggadottir SM, Li J, Glessner JT, Li YR, Wei Z, Chang X, et al. Rare variants at 16p11.2 are associated with common variable immunodeficiency. J. Allergy Clin. Immunol. 2015;135:1569–77.PubMedPubMedCentral
15.
go back to reference Rodríguez-Cortez VC, Del Pino-Molina L, Rodríguez-Ubreva J, Ciudad L, Gómez-Cabrero D, Company C, et al. Monozygotic twins for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition. Nat Commun. 2015;6:7335.PubMed Rodríguez-Cortez VC, Del Pino-Molina L, Rodríguez-Ubreva J, Ciudad L, Gómez-Cabrero D, Company C, et al. Monozygotic twins for common variable immunodeficiency reveal impaired DNA demethylation during naïve-to-memory B-cell transition. Nat Commun. 2015;6:7335.PubMed
16.
go back to reference Tabak LA. A revolution in biomedical assessment: the development of salivary diagnostics. J Dent Educ. 2001;65:1335–9.PubMed Tabak LA. A revolution in biomedical assessment: the development of salivary diagnostics. J Dent Educ. 2001;65:1335–9.PubMed
17.
go back to reference Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DT. Salivary biomarkers: toward future clinical and diagnostic utilities. Clin Microbiol Rev. 2013;26:781–91.PubMedPubMedCentral Yoshizawa JM, Schafer CA, Schafer JJ, Farrell JJ, Paster BJ, Wong DT. Salivary biomarkers: toward future clinical and diagnostic utilities. Clin Microbiol Rev. 2013;26:781–91.PubMedPubMedCentral
18.
go back to reference Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C. Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011;57:675–87.PubMed Pfaffe T, Cooper-White J, Beyerlein P, Kostner K, Punyadeera C. Diagnostic potential of saliva: current state and future applications. Clin Chem. 2011;57:675–87.PubMed
19.
go back to reference Cabras T, Iavarone F, Manconi B, Olianas A, Sanna MT, Castagnola M, et al. Top-down analytical platforms for the characterization of the human salivary proteome. Bioanalysis. 2014;6:563–81.PubMed Cabras T, Iavarone F, Manconi B, Olianas A, Sanna MT, Castagnola M, et al. Top-down analytical platforms for the characterization of the human salivary proteome. Bioanalysis. 2014;6:563–81.PubMed
20.
go back to reference Bandhakavi S, Stone MD, Onsongo G, Van Riper SK, Griffin TJ. A dynamic range compression and three-dimensional peptide fractionation analysis platform expands proteome coverage and the diagnostic potential of whole saliva. J Proteome Res. 2009;8:5590–600.PubMedPubMedCentral Bandhakavi S, Stone MD, Onsongo G, Van Riper SK, Griffin TJ. A dynamic range compression and three-dimensional peptide fractionation analysis platform expands proteome coverage and the diagnostic potential of whole saliva. J Proteome Res. 2009;8:5590–600.PubMedPubMedCentral
21.
go back to reference Castagnola M, Cabras T, Iavarone F, Fanali C, Nemolato S, Peluso G, et al. The human salivary proteome: a critical overview of the results obtained by different proteomic platforms. Expert Rev Proteomics. 2012;9:33–46.PubMed Castagnola M, Cabras T, Iavarone F, Fanali C, Nemolato S, Peluso G, et al. The human salivary proteome: a critical overview of the results obtained by different proteomic platforms. Expert Rev Proteomics. 2012;9:33–46.PubMed
22.
go back to reference Oh SS, Park S, Lee KW, Madhi H, Park SG, Lee HG, et al. Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation. Cell Death Dis. 2017;8:e2729.PubMedPubMedCentral Oh SS, Park S, Lee KW, Madhi H, Park SG, Lee HG, et al. Extracellular cystatin SN and cathepsin B prevent cellular senescence by inhibiting abnormal glycogen accumulation. Cell Death Dis. 2017;8:e2729.PubMedPubMedCentral
23.
go back to reference Yoneda K, Iida H, Endo H, Hosono K, Akiyama T, Takahashi H, et al. Identification of Cystatin SN as a novel tumor marker for colorectal cancer. Int J Oncol. 2009;35:33–40.PubMed Yoneda K, Iida H, Endo H, Hosono K, Akiyama T, Takahashi H, et al. Identification of Cystatin SN as a novel tumor marker for colorectal cancer. Int J Oncol. 2009;35:33–40.PubMed
24.
go back to reference Zhang Z, Marshall AG. An universal algorithm for fast and automated charge state deconvolution of electrospray mass-to-charge ratio spectra. J Am Soc Mass Spectrom. 1998;9:225–33.PubMed Zhang Z, Marshall AG. An universal algorithm for fast and automated charge state deconvolution of electrospray mass-to-charge ratio spectra. J Am Soc Mass Spectrom. 1998;9:225–33.PubMed
25.
go back to reference Castagnola M, Cabras T, Iavarone F, Vincenzoni F, Vitali A, Pisano E, et al. Top-down platform for deciphering the human salivary proteome. J Matern Fetal Neonatal Med. 2012;25:27–43.PubMed Castagnola M, Cabras T, Iavarone F, Vincenzoni F, Vitali A, Pisano E, et al. Top-down platform for deciphering the human salivary proteome. J Matern Fetal Neonatal Med. 2012;25:27–43.PubMed
26.
go back to reference Manconi B, Liori B, Cabras T, Vincenzoni F, Iavarone F, Lorefice L, et al. Top-down proteomic profiling of human saliva in multiple sclerosis patients. J Proteome. 2018;187:212–22. Manconi B, Liori B, Cabras T, Vincenzoni F, Iavarone F, Lorefice L, et al. Top-down proteomic profiling of human saliva in multiple sclerosis patients. J Proteome. 2018;187:212–22.
27.
go back to reference Messana I, Cabras T, Pisano E, Sanna MT, Olianas A, Manconi B, et al. Trafficking and postsecretory events responsible for the formation of secreted human salivary peptide: a proteomics approach. Mol Cell Proteomics. 2008;7:911–26.PubMed Messana I, Cabras T, Pisano E, Sanna MT, Olianas A, Manconi B, et al. Trafficking and postsecretory events responsible for the formation of secreted human salivary peptide: a proteomics approach. Mol Cell Proteomics. 2008;7:911–26.PubMed
28.
go back to reference Inzitari R, Cabras T, Pisano E, Fanali C, Manconi B, Scarano E, et al. HPLC-ESI-MS analysis of oral human fluids reveals that gingival crevicular fluid is the main source of oral thymosins beta(4) and beta(10). J Sep Sci. 2009;32:57–63.PubMed Inzitari R, Cabras T, Pisano E, Fanali C, Manconi B, Scarano E, et al. HPLC-ESI-MS analysis of oral human fluids reveals that gingival crevicular fluid is the main source of oral thymosins beta(4) and beta(10). J Sep Sci. 2009;32:57–63.PubMed
29.
go back to reference Cabras T, Manconi B, Iavarone F, Fanali C, Nemolato S, Fiorita A, et al. RP-HPLC-ESI-MS evidenced that salivary cystatin B is detectable in adult human whole saliva mostly as S-modified derivatives: S-Glutathionyl, S-cysteinyl and S-S 2-mer. J Proteome. 2012;75:908–13. Cabras T, Manconi B, Iavarone F, Fanali C, Nemolato S, Fiorita A, et al. RP-HPLC-ESI-MS evidenced that salivary cystatin B is detectable in adult human whole saliva mostly as S-modified derivatives: S-Glutathionyl, S-cysteinyl and S-S 2-mer. J Proteome. 2012;75:908–13.
30.
go back to reference Manconi B, Liori B, Cabras T, Vincenzoni F, Iavarone F, Castagnola M, et al. Salivary cystatins: exploring new post-translational modifications and polymorphisms by top-down high-resolution mass spectrometry. J Proteome Res. 2017;16:4196–07.PubMed Manconi B, Liori B, Cabras T, Vincenzoni F, Iavarone F, Castagnola M, et al. Salivary cystatins: exploring new post-translational modifications and polymorphisms by top-down high-resolution mass spectrometry. J Proteome Res. 2017;16:4196–07.PubMed
31.
go back to reference Cabras T, Pisano E, Montaldo C, Giuca MR, Iavarone F, Zampino G, et al. Significant modifications of the salivary proteome potentially associated with complications of Down syndrome revealed by top-down proteomics. Mol Cell Proteomics. 2013;12:1844–52.PubMedPubMedCentral Cabras T, Pisano E, Montaldo C, Giuca MR, Iavarone F, Zampino G, et al. Significant modifications of the salivary proteome potentially associated with complications of Down syndrome revealed by top-down proteomics. Mol Cell Proteomics. 2013;12:1844–52.PubMedPubMedCentral
32.
go back to reference Cabras T, Pisano E, Mastinu A, Denotti G, Pusceddu PP, Inzitari R, et al. Alterations of the salivary secretory peptidome profile in children affected by type 1 diabetes. Mol Cell Proteomics. 2010;9:2099–108.PubMedPubMedCentral Cabras T, Pisano E, Mastinu A, Denotti G, Pusceddu PP, Inzitari R, et al. Alterations of the salivary secretory peptidome profile in children affected by type 1 diabetes. Mol Cell Proteomics. 2010;9:2099–108.PubMedPubMedCentral
33.
go back to reference Cabras T, Sanna M, Manconi B, Fanni D, Demelia L, Sorbello O, et al. Proteomic investigation of whole saliva in Wilson's disease. J Proteome. 2015;128:154–63. Cabras T, Sanna M, Manconi B, Fanni D, Demelia L, Sorbello O, et al. Proteomic investigation of whole saliva in Wilson's disease. J Proteome. 2015;128:154–63.
34.
go back to reference Castagnola M, Inzitari R, Fanali C, Iavarone F, Vitali A, Desiderio C, et al. The surprising composition of the salivary proteome of preterm human newborn. Mol Cell Proteomics. 2011;10:M110.003467.PubMed Castagnola M, Inzitari R, Fanali C, Iavarone F, Vitali A, Desiderio C, et al. The surprising composition of the salivary proteome of preterm human newborn. Mol Cell Proteomics. 2011;10:M110.003467.PubMed
35.
go back to reference Ong SE, Mann M. Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol. 2005;1:252–62.PubMed Ong SE, Mann M. Mass spectrometry-based proteomics turns quantitative. Nat Chem Biol. 2005;1:252–62.PubMed
36.
go back to reference Messana I, Inzitari R, Fanali C, Cabras T, Castagnola M. Facts and artifacts in proteomics of body fluids. What proteomics of saliva is telling us? J Sep Sci. 2008;31:1948–63.PubMed Messana I, Inzitari R, Fanali C, Cabras T, Castagnola M. Facts and artifacts in proteomics of body fluids. What proteomics of saliva is telling us? J Sep Sci. 2008;31:1948–63.PubMed
37.
go back to reference Vizcaíno JA, Csordas A, del-Toro N, Dianes JA, Griss J, Lavidas I, et al. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res. 2016;44(D1):D447–56.PubMed Vizcaíno JA, Csordas A, del-Toro N, Dianes JA, Griss J, Lavidas I, et al. 2016 update of the PRIDE database and its related tools. Nucleic Acids Res. 2016;44(D1):D447–56.PubMed
38.
go back to reference Arba M, Iavarone F, Vincenzoni F, Manconi B, Vento G, Tirone C, et al. Proteomic characterization of the acid-insoluble fraction of whole saliva from preterm human newborns. J Proteome. 2016;2(146):48–57. Arba M, Iavarone F, Vincenzoni F, Manconi B, Vento G, Tirone C, et al. Proteomic characterization of the acid-insoluble fraction of whole saliva from preterm human newborns. J Proteome. 2016;2(146):48–57.
39.
go back to reference Cabras T, Pisano E, Boi R, Olianas A, Manconi B, Inzitari R, et al. Age-dependent modifications of the human salivary secretory protein complex. J Proteome Res. 2009;8:4126–34.PubMed Cabras T, Pisano E, Boi R, Olianas A, Manconi B, Inzitari R, et al. Age-dependent modifications of the human salivary secretory protein complex. J Proteome Res. 2009;8:4126–34.PubMed
40.
go back to reference Cabras T, Melis M, Castagnola M, Padiglia A, Tepper BJ, Messana I, et al. Responsiveness to 6-n-propylthiouracil (PROP) is associated with salivary levels of two specific basic proline-rich proteins in humans. PLoS One. 2012;7:e30962.PubMedPubMedCentral Cabras T, Melis M, Castagnola M, Padiglia A, Tepper BJ, Messana I, et al. Responsiveness to 6-n-propylthiouracil (PROP) is associated with salivary levels of two specific basic proline-rich proteins in humans. PLoS One. 2012;7:e30962.PubMedPubMedCentral
41.
go back to reference Padiglia A, Orrù R, Boroumand M, Olianas A, Manconi B, Sanna MT, et al. Extensive characterization of the human salivary basic proline-rich protein family by top-down mass spectrometry. J Proteome Res. 2018;17:3292–07.PubMed Padiglia A, Orrù R, Boroumand M, Olianas A, Manconi B, Sanna MT, et al. Extensive characterization of the human salivary basic proline-rich protein family by top-down mass spectrometry. J Proteome Res. 2018;17:3292–07.PubMed
42.
43.
go back to reference Dale BA, Fredericks LP. Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol. 2005;7:119–33.PubMedPubMedCentral Dale BA, Fredericks LP. Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol. 2005;7:119–33.PubMedPubMedCentral
44.
go back to reference Pisano E, Cabras T, Montaldo C, Piras V, Inzitari R, Olmi C, et al. Peptides of human gingival crevicular fluid determinated by HPLC-ESI-IT-MS. Eur J Oral Sci. 2005;11:462–8. Pisano E, Cabras T, Montaldo C, Piras V, Inzitari R, Olmi C, et al. Peptides of human gingival crevicular fluid determinated by HPLC-ESI-IT-MS. Eur J Oral Sci. 2005;11:462–8.
45.
46.
go back to reference Chalifour A, Jeannin P, Gauchat JF, Blaecke A, Malissard M, N’Guyen T, et al. Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood. 2004;104:1778–83.PubMed Chalifour A, Jeannin P, Gauchat JF, Blaecke A, Malissard M, N’Guyen T, et al. Direct bacterial protein PAMP recognition by human NK cells involves TLRs and triggers alpha-defensin production. Blood. 2004;104:1778–83.PubMed
47.
go back to reference Hazlett L, Wu M. Defensins in innate immunity. Cell Tissue Res. 2011;343:175–88.PubMed Hazlett L, Wu M. Defensins in innate immunity. Cell Tissue Res. 2011;343:175–88.PubMed
48.
go back to reference Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000;96:3086–93.PubMed Agerberth B, Charo J, Werr J, Olsson B, Idali F, Lindbom L, et al. The human antimicrobial and chemotactic peptides LL-37 and alpha-defensins are expressed by specific lymphocyte and monocyte populations. Blood. 2000;96:3086–93.PubMed
49.
go back to reference Vordenbäumen S, Schneider M. Defensins: potential effectors in autoimmune rheumatic disorders. Polymers. 2011;3:1268–81. Vordenbäumen S, Schneider M. Defensins: potential effectors in autoimmune rheumatic disorders. Polymers. 2011;3:1268–81.
50.
go back to reference Becker SC, Szyska M, Mensen A, Hellwig K, Otto R, Olfe L, et al. A comparative analysis of human bone marrow–resident and peripheral memory B cells. J allergy Clyn Immunol. 2018;141:1911–3. Becker SC, Szyska M, Mensen A, Hellwig K, Otto R, Olfe L, et al. A comparative analysis of human bone marrow–resident and peripheral memory B cells. J allergy Clyn Immunol. 2018;141:1911–3.
51.
go back to reference Agarwal S, Mayer L. Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency. Clin Gastroenterol Hepatol. 2013;11:1050–63.PubMedPubMedCentral Agarwal S, Mayer L. Diagnosis and treatment of gastrointestinal disorders in patients with primary immunodeficiency. Clin Gastroenterol Hepatol. 2013;11:1050–63.PubMedPubMedCentral
52.
go back to reference van de Ven AAJM, Janssen WJM, Schulz LS, van Loon AM, Voorkamp K, EAM S, et al. increased prevalence of gastrointestinal viruses and diminished secretory immunoglobulin a levels in antibody deficiencies. J Clin Immunol. 2014;34:962–70.PubMed van de Ven AAJM, Janssen WJM, Schulz LS, van Loon AM, Voorkamp K, EAM S, et al. increased prevalence of gastrointestinal viruses and diminished secretory immunoglobulin a levels in antibody deficiencies. J Clin Immunol. 2014;34:962–70.PubMed
53.
go back to reference Gounder AP, Myers ND, Treuting PM, Bromme BA, Wilson SS, Wiens ME, et al. Defensins potentiate a neutralizing antibody response to enteric viral infection. PLoS Pathog. 2016;12:e1005474.PubMedPubMedCentral Gounder AP, Myers ND, Treuting PM, Bromme BA, Wilson SS, Wiens ME, et al. Defensins potentiate a neutralizing antibody response to enteric viral infection. PLoS Pathog. 2016;12:e1005474.PubMedPubMedCentral
54.
go back to reference Chaly YV, Paleolog EM, Kolesnikova TS, Tikhonov II, Petratchenko EV, Voitenok NN. Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw. 2000;11:257–66.PubMed Chaly YV, Paleolog EM, Kolesnikova TS, Tikhonov II, Petratchenko EV, Voitenok NN. Neutrophil alpha-defensin human neutrophil peptide modulates cytokine production in human monocytes and adhesion molecule expression in endothelial cells. Eur Cytokine Netw. 2000;11:257–66.PubMed
55.
go back to reference Ryan CM, Souda P, Halgand F, Wong DT, Loo JA, Faull KF, et al. Confident assignment of intact mass tags to human salivary cystatins using top-down Fourier-transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom. 2010;21:908–17.PubMedPubMedCentral Ryan CM, Souda P, Halgand F, Wong DT, Loo JA, Faull KF, et al. Confident assignment of intact mass tags to human salivary cystatins using top-down Fourier-transform ion cyclotron resonance mass spectrometry. J Am Soc Mass Spectrom. 2010;21:908–17.PubMedPubMedCentral
56.
go back to reference Dickinson DP. Salivary (SD-type) cystatins: over one billion years in the making-but to what purpose? Crit Rev Oral Biol Med. 2002;13:485–08.PubMed Dickinson DP. Salivary (SD-type) cystatins: over one billion years in the making-but to what purpose? Crit Rev Oral Biol Med. 2002;13:485–08.PubMed
57.
go back to reference Hopsu-Havu VK, Joronen IA, Järvinen M, Rinne A, Aalto M. Cysteine proteinase inhibitors produced by mononuclear phagocytes. Cell Tissue Res. 1984;236:161–4.PubMed Hopsu-Havu VK, Joronen IA, Järvinen M, Rinne A, Aalto M. Cysteine proteinase inhibitors produced by mononuclear phagocytes. Cell Tissue Res. 1984;236:161–4.PubMed
58.
go back to reference Suzuki T, Hashimoto S, Toyoda N, Nagai S, Yamazaki N, Dong HY, et al. Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE. Blood. 2000;96:2584–91.PubMed Suzuki T, Hashimoto S, Toyoda N, Nagai S, Yamazaki N, Dong HY, et al. Comprehensive gene expression profile of LPS-stimulated human monocytes by SAGE. Blood. 2000;96:2584–91.PubMed
59.
go back to reference Yang F, Tay KH, Dong L, Thorne RF, Jiang CC, Yang E, et al. Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIP(L) from degradation by the E3 ligase itch in human melanoma cells. Cell Death Differ. 2010;17:1354–67.PubMed Yang F, Tay KH, Dong L, Thorne RF, Jiang CC, Yang E, et al. Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIP(L) from degradation by the E3 ligase itch in human melanoma cells. Cell Death Differ. 2010;17:1354–67.PubMed
60.
go back to reference Ceru S, Konjar S, Maher K, Repnik U, Krizaj I, Bencina M, et al. Stefin B interacts with histones and cathepsin L in the nucleus. J Biol Chem. 2010;285:10078–86.PubMedPubMedCentral Ceru S, Konjar S, Maher K, Repnik U, Krizaj I, Bencina M, et al. Stefin B interacts with histones and cathepsin L in the nucleus. J Biol Chem. 2010;285:10078–86.PubMedPubMedCentral
61.
go back to reference Maher K, Jerič Kokelj B, Butinar M, Mikhaylov G, Manček-Keber M, Stoka V, et al. Role for Stefin B (Cystatin B) in inflammation and Endotoxemia. J Biol Chem. 2014;289:31736–50.PubMedPubMedCentral Maher K, Jerič Kokelj B, Butinar M, Mikhaylov G, Manček-Keber M, Stoka V, et al. Role for Stefin B (Cystatin B) in inflammation and Endotoxemia. J Biol Chem. 2014;289:31736–50.PubMedPubMedCentral
62.
go back to reference Lehtinen MK, Tegelberg S, Schipper H, Su H, Zukor H, Manninen O, et al. Cystatin B deficiency sensitizes neurons to oxidative stress in progressive myoclonus epilepsy, EPM1. J Neurosci. 2009;29:5910–5.PubMedPubMedCentral Lehtinen MK, Tegelberg S, Schipper H, Su H, Zukor H, Manninen O, et al. Cystatin B deficiency sensitizes neurons to oxidative stress in progressive myoclonus epilepsy, EPM1. J Neurosci. 2009;29:5910–5.PubMedPubMedCentral
64.
go back to reference Polajnar M, Ceru S, Kopitar-Jerala N, Zerovnik E. Human stefin B normal and patho-physiological role: molecular and cellular aspects of amyloid-type aggregation of certain EPM1 mutants. Frontiers Mol Neurosci. 2012;5:88. Polajnar M, Ceru S, Kopitar-Jerala N, Zerovnik E. Human stefin B normal and patho-physiological role: molecular and cellular aspects of amyloid-type aggregation of certain EPM1 mutants. Frontiers Mol Neurosci. 2012;5:88.
65.
go back to reference Aukrust P, Berge RK, Muller F, Ueland PM, Svardal AM, Froland SS. Elevated plasma levels of reduced homocysteine in common variable immunodeficiency - a marker of enhanced oxidative stress. Eur J Clin Investig. 1997;27:723–30. Aukrust P, Berge RK, Muller F, Ueland PM, Svardal AM, Froland SS. Elevated plasma levels of reduced homocysteine in common variable immunodeficiency - a marker of enhanced oxidative stress. Eur J Clin Investig. 1997;27:723–30.
66.
go back to reference Fábián TK, Hermann P, Beck A, Fejérdy P, Fábián G. Salivary defense proteins: their network and role in innate and acquired oral immunity. Int J Mol Sci. 2012;13:4295–320.PubMedPubMedCentral Fábián TK, Hermann P, Beck A, Fejérdy P, Fábián G. Salivary defense proteins: their network and role in innate and acquired oral immunity. Int J Mol Sci. 2012;13:4295–320.PubMedPubMedCentral
67.
go back to reference Zavasnik-Bergant T. Cystatin protease inhibitor and immune function. Front Biosci. 2008;13:4625–37.PubMed Zavasnik-Bergant T. Cystatin protease inhibitor and immune function. Front Biosci. 2008;13:4625–37.PubMed
68.
go back to reference Ruzindana-Umunyana A, Weber JM. Interactions of human lacrimal and salivary cystatins with adenovirus endopeptidase. Antivir Res. 2001;51:203–14.PubMed Ruzindana-Umunyana A, Weber JM. Interactions of human lacrimal and salivary cystatins with adenovirus endopeptidase. Antivir Res. 2001;51:203–14.PubMed
69.
go back to reference Magister S, Kos J. Cystatins in immune system. J Cancer. 2013;4:45–56.PubMed Magister S, Kos J. Cystatins in immune system. J Cancer. 2013;4:45–56.PubMed
70.
go back to reference Lindh E, Brӓnnstrӧm J, Jones P, Wermeling F, Hӓssler S, Betterle C, et al. Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type 1. J Autoimmun. 2013;42:1–6.PubMed Lindh E, Brӓnnstrӧm J, Jones P, Wermeling F, Hӓssler S, Betterle C, et al. Autoimmunity and cystatin SA1 deficiency behind chronic mucocutaneous candidiasis in autoimmune polyendocrine syndrome type 1. J Autoimmun. 2013;42:1–6.PubMed
71.
go back to reference Baron A, DeCarlo A, Featherstone J. Functional aspects of the human salivary cystatins in the oral environment. Oral Dis. 1999;5:234–40.PubMed Baron A, DeCarlo A, Featherstone J. Functional aspects of the human salivary cystatins in the oral environment. Oral Dis. 1999;5:234–40.PubMed
72.
go back to reference Cao X, Li Y, Luo RZ, Zhang L, Zhang SL, Zeng J, et al. Expression of Cystatin SN significantly correlates with recurrence, metastasis, and survival duration in surgically resected non-small cell lung cancer patients. Scientifc Reports. 2015;5:8230. Cao X, Li Y, Luo RZ, Zhang L, Zhang SL, Zeng J, et al. Expression of Cystatin SN significantly correlates with recurrence, metastasis, and survival duration in surgically resected non-small cell lung cancer patients. Scientifc Reports. 2015;5:8230.
73.
go back to reference Dai DN, Li Y, Chen B, Du Y, Li SB, Lu SX, et al. Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis. J. Mol. Med. 2017;95:873–86.PubMed Dai DN, Li Y, Chen B, Du Y, Li SB, Lu SX, et al. Elevated expression of CST1 promotes breast cancer progression and predicts a poor prognosis. J. Mol. Med. 2017;95:873–86.PubMed
74.
go back to reference Jiang J, Liu HL, Liu ZH, Tan SW, Wu B. Identification of cystatin SN as a novel biomarker for pancreatic cancer. Tumor Biol. 2015;36:3903–10. Jiang J, Liu HL, Liu ZH, Tan SW, Wu B. Identification of cystatin SN as a novel biomarker for pancreatic cancer. Tumor Biol. 2015;36:3903–10.
75.
go back to reference Mayor PC, Eng KH, Singel KL, Abrams SI, Odunsi K, Moysich KB, et al. Cancer in primary immunodeficiency diseases: cancer incidence in the United States immune deficiency network registry. J Allergy Clin Immunol. 2018;141:1028–35.PubMed Mayor PC, Eng KH, Singel KL, Abrams SI, Odunsi K, Moysich KB, et al. Cancer in primary immunodeficiency diseases: cancer incidence in the United States immune deficiency network registry. J Allergy Clin Immunol. 2018;141:1028–35.PubMed
Metadata
Title
RP-HPLC-ESI-IT Mass Spectrometry Reveals Significant Variations of the Human Salivary Protein Profile Associated with Predominantly Antibody Deficiencies
Authors
Cristina Contini
Davide Firinu
Simone Serrao
Barbara Manconi
Alessandra Olianas
Francesco Cinetto
Fausto Cossu
Massimo Castagnola
Irene Messana
Stefano Del Giacco
Tiziana Cabras
Publication date
01-02-2020
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 2/2020
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-020-00743-4

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