TY - JOUR
T1 - Prolactin-Induced Protein is a novel biomarker for Keratoconus
AU - Sharif, Rabab
AU - Bak-Nielsen, Sashia
AU - Sejersen, Henrik
AU - Ding, Kai
AU - Hjortdal, Jesper
AU - Karamichos, Dimitrios
N1 - Funding Information:
Authors would like to acknowledge the support of the National Institute of Health (NEI) Grant EY028888 (DK), unrestricted grant (DMEI) from Research to Prevent Blindness (New York, NY USA), and Synoptik Fonden , Fight for Sight , Denmark, Aarhus University and Einar Willumsens Mindelegat, The funding organizations had no role in study design or conduct of this research.
Funding Information:
Authors would like to acknowledge the support of the National Institute of Health (NEI) Grant EY028888 (DK), unrestricted grant (DMEI) from Research to Prevent Blindness (New York, NY USA), and Synoptik Fonden, Fight for Sight, Denmark, Aarhus University and Einar Willumsens Mindelegat, The funding organizations had no role in study design or conduct of this research.
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/2
Y1 - 2019/2
N2 - Purpose: The purpose of the study was to investigate the role of Prolactin-Induced Protein (PIP) as a predictive biomarker for Keratoconus (KC). Participants: This study included one hundred and forty-seven patients with KC (105 male, 42 female), and sixty healthy controls (27 male, 33 female). Methods: Tears, plasma and saliva samples were collected from all participants. In both KC and healthy groups all collected samples were divided into four age subgroups (15-24y), (25-34y), (35-44y) and (45y and up). Samples were analyzed using western blot (WB) and enzyme-linked immunosorbent assay (ELISA). Areas under the receiver operating characteristic curves (AUROCs) were used to evaluate diagnostic accuracy for distinguishing between KC and healthy eyes. Main outcome measures: Difference in PIP protein levels between patients with KC and healthy controls. Results: Results showed significant downregulation of PIP expression in all three biological fluids on KC patients when compared to healthy controls, independent of age, sex and severity. Since PIP is a hormonal-regulated protein, we also investigated the expression of major sex hormones. We detected significant upregulation in salivary and plasma Dehydroepiandrosterone sulfate (DHEA-S) levels and significant downregulation of estrone and estriol levels, in KC patients compared to healthy controls, independent of sex, age, and KC severity stage. ROC was used to determine the overall predictive accuracy of this protein in KC. Data showed an area under the curve (AUC) for PIP in tears of 0.937 (95%CI: 0.902–0.971), in plasma of 0.928 (95%CI: 0.890–0.968) and in saliva of 0.929 (95%CI: 0.890–0.968). Conclusions: Conclusively, our results show that PIP levels are reduced in all three human biological fluids tested, and may independently or in combination with current imaging techniques aid in screening and diagnosis of KC. Our data revealed that PIP levels can potentially differentiate between disease and healthy cases, and PIP levels are stable in relation to KC severity, sex and age. Moreover, alterations in sex hormone levels in correlation with reduced PIP levels in KC provide an intriguing insight in the underlying KC pathophysiology and highlights the role of PIP as a KC biomarker.
AB - Purpose: The purpose of the study was to investigate the role of Prolactin-Induced Protein (PIP) as a predictive biomarker for Keratoconus (KC). Participants: This study included one hundred and forty-seven patients with KC (105 male, 42 female), and sixty healthy controls (27 male, 33 female). Methods: Tears, plasma and saliva samples were collected from all participants. In both KC and healthy groups all collected samples were divided into four age subgroups (15-24y), (25-34y), (35-44y) and (45y and up). Samples were analyzed using western blot (WB) and enzyme-linked immunosorbent assay (ELISA). Areas under the receiver operating characteristic curves (AUROCs) were used to evaluate diagnostic accuracy for distinguishing between KC and healthy eyes. Main outcome measures: Difference in PIP protein levels between patients with KC and healthy controls. Results: Results showed significant downregulation of PIP expression in all three biological fluids on KC patients when compared to healthy controls, independent of age, sex and severity. Since PIP is a hormonal-regulated protein, we also investigated the expression of major sex hormones. We detected significant upregulation in salivary and plasma Dehydroepiandrosterone sulfate (DHEA-S) levels and significant downregulation of estrone and estriol levels, in KC patients compared to healthy controls, independent of sex, age, and KC severity stage. ROC was used to determine the overall predictive accuracy of this protein in KC. Data showed an area under the curve (AUC) for PIP in tears of 0.937 (95%CI: 0.902–0.971), in plasma of 0.928 (95%CI: 0.890–0.968) and in saliva of 0.929 (95%CI: 0.890–0.968). Conclusions: Conclusively, our results show that PIP levels are reduced in all three human biological fluids tested, and may independently or in combination with current imaging techniques aid in screening and diagnosis of KC. Our data revealed that PIP levels can potentially differentiate between disease and healthy cases, and PIP levels are stable in relation to KC severity, sex and age. Moreover, alterations in sex hormone levels in correlation with reduced PIP levels in KC provide an intriguing insight in the underlying KC pathophysiology and highlights the role of PIP as a KC biomarker.
KW - Biomarker
KW - Blood
KW - Keratoconus
KW - Prolactin-Induced Protein
KW - Saliva
KW - Tears
UR - http://www.scopus.com/inward/record.url?scp=85055910382&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2018.10.015
DO - 10.1016/j.exer.2018.10.015
M3 - Article
C2 - 30393162
AN - SCOPUS:85055910382
SN - 0014-4835
VL - 179
SP - 55
EP - 63
JO - Experimental Eye Research
JF - Experimental Eye Research
ER -