Tear Film Proteomics Reveal Important Differences Between Patients With and Without Ocular GvHD After Allogeneic Hematopoietic Cell Transplantation

Gerber-Hollbach, Nadine; Plattner, Kim David; O'Leary, Olivia; Jenoe, Paul; Moes, Suzette; Drexler, Beatrice; Schoetzau, Andreas; Halter, Jörg; Goldblum, David

doi:10.1167/iovs.18-24433

Cited by 26 publications

(30 citation statements)

References 58 publications

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“… 16 To our knowledge, we were the first group to use untargeted proteomic methods to investigate oGVHD tear protein expression. 18 In this way, we have broadened the number of investigated targets beyond inflammatory pathways alone.…”

Section: Discussionmentioning

confidence: 99%

“…Mass spectrometric analysis of tear proteins was performed as described in detail previously. 18 In brief, tryptic digests were prepared from small pieces of Schirmer test strips and acidified with trifluoroacetic acid (TFA; Applied Biosystems, Rotkreuz, Switzerland) at a 1% final concentration. Peptides were desalted on C18 SepPak cartridges (Waters, Dättwil, Switzerland) and washed with a solution of 0.1% TFA.…”

Section: Methodsmentioning

confidence: 99%

“…Forty-microliter aliquots of sample were prepared for analysis by liquid chromatography tandem mass spectrometry (LC-MS/MS) using an Orbitrap FT hybrid system (Thermo Fisher Scientific, Waltham, MA, USA). Full details of the injection and flow parameters are provided by Gerber-Hollbach et al 18 …”

Section: Methodsmentioning

confidence: 99%

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Tear Proteomic Predictive Biomarker Model for Ocular Graft Versus Host Disease Classification

O'Leary

Schoetzau

Amruthalingam

et al. 2020

Trans. Vis. Sci. Tech.

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Purpose Diagnosis of ocular graft-versus-host disease (oGVHD) is hampered by a lack of clinically-validated biomarkers. This study aims to predict disease severity on the basis of tear protein expression in mild oGVHD. Methods Forty-nine patients with and without chronic oGVHD after AHCT were recruited to a cross-sectional observational study. Patients were stratified using NIH guidelines for oGVHD severity: NIH 0 (none; n = 14), NIH 1 (mild; n = 9), NIH 2 (moderate; n = 16), and NIH 3 (severe; n = 10). The proteomic profile of tears was analyzed using liquid chromatography-tandem mass spectrometry. Random forest and penalized logistic regression were used to generate classification and prediction models to stratify patients according to disease severity. Results Mass spectrometry detected 785 proteins across all samples. A random forest model used to classify patients by disease grade achieved F1-measure values for correct classification of 0.95 (NIH 0), 0.8 (NIH 1), 0.74 (NIH 2), and 0.83 (NIH 3). A penalized logistic regression model was generated by comparing patients without oGVHD and those with mild oGVHD and applied to identify potential biomarkers present early in disease. A panel of 13 discriminant markers achieved significant diagnostic accuracy in identifying patients with moderate-to-severe disease. Conclusions Our work demonstrates the utility of tear protein biomarkers in classifying oGVHD severity and adds further evidence indicating ocular surface inflammation as a main driver of oGVHD clinical phenotype. Translational Relevance Expression levels of a 13-marker tear protein panel in AHCT patients with mild oGVHD may predict development of more severe oGVHD clinical phenotypes.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Tear Proteomic Predictive Biomarker Model for Ocular Graft Versus Host Disease Classification

O'Leary

Schoetzau

Amruthalingam

et al. 2020

Trans. Vis. Sci. Tech.

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“…Ocular GVHD mimics severe ADDE, damaging the patient's quality of life. [1316] Unlike SS where the histological picture is characterized by lymphocyte infiltrate of lacrimal glands, GVHD is characterized by lacrimal gland fibrosis. SJS, and its severe form, toxic epidermal necrolysis, are acute exfoliative blistering disorders of the skin, following adverse drug reactions.…”

Section: Use Of Tear Film Biomarkers In Dry Eye With Systemic Inflammmentioning

confidence: 99%

“…The use of a biomarker will lead to better diagnosis, categorization, and more effective management of DED. [1314] Using biomarkers in tear film is very desirable owing to the fact that we can obtain them in a noninvasive and accessible manner. In addition, it is anatomically close to the disease site, increasing the specificity for ocular surface inflammatory disease.…”

Section: Introductionmentioning

confidence: 99%

Role of tear film biomarkers in the diagnosis and management of dry eye disease

Fong

Shih

Lam

et al. 2019

Taiwan J Ophthalmol

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In recent years, there has been increasing scientific interest in the use of tear film biomarkers in the diagnosis and management of dry eye disease (DED), owing to their potential important roles in the pathogenesis of ocular surface damage, as well as the technical feasibility of tear sample collection techniques. An Entrez PubMed search was conducted on March 2, 2019, to include papers investigating the use of tear film biomarkers in DED, and the results were classified according to whether the DED is associated with systemic inflammatory disease or not and further classified within each section according to the molecular nature of the biomarker for further discussion. A total of 58 relevant articles were reviewed. Certain cytokines, including interleukin-6 (IL-6), tumor necrosis factor-alpha, IL-17, and IL-8, were found by a number of studies to consistently reflect disease severity well and had strong correlations with tear film metrics and tests for ocular surface damage in dry eye without systemic inflammatory disease. For dry eye with systemic inflammatory disease, IL-17, IL-8, and IL-1 receptor antagonists were shown to be consistently higher in affected eyes and correlated well with ocular surface disease severity in more than one type of inflammatory disease. With the advancement in technology and lowered costs in the future, tear film biomarker counts would allow better diagnosis and monitoring of DED, as well as facilitate personalized treatment strategies.

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Ocular surface system alterations in ocular graft-versus-host disease: all the pieces of the complex puzzle

Giannaccare

Pellegrini

Bernabei

et al. 2019

Graefes Arch Clin Exp Ophthalmol

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Tear Film Proteomics Reveal Important Differences Between Patients With and Without Ocular GvHD After Allogeneic Hematopoietic Cell Transplantation

Cited by 26 publications

References 58 publications

Tear Proteomic Predictive Biomarker Model for Ocular Graft Versus Host Disease Classification

Tear Proteomic Predictive Biomarker Model for Ocular Graft Versus Host Disease Classification

Role of tear film biomarkers in the diagnosis and management of dry eye disease

Ocular surface system alterations in ocular graft-versus-host disease: all the pieces of the complex puzzle

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