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Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

ABSTRACT: Keratoconus (KC) is classically considered a non-inflammatory condition caused by central corneal thinning that leads to astigmatism and reduced visual acuity. Previous studies have identified increased systemic levels of pro-inflammatory factors, including interleukin-6, tumor necrosis factor-?, and matrix metalloproteinase-9, suggesting that KC may have an inflammatory component in at least a subset of patients. In this study, we evaluated the levels of different immunoglobulins (light and heavy chains) based on Ig ?, Ig ?, Ig ?, Ig µ, and Ig heavy chain subunits in non-KC tears (n?=?7 control individuals) and KC tears (n?=?7 KC patients) using tandem-liquid chromatography mass spectrometry. The most abundant Ig heavy chains detected in both control individuals and KC patients were Ig ?-1 and Ig ?-2 likely correlating to the higher IgA levels reported in human tears. We identified significant differences in immunoglobulin ?-chain V-II levels in KC patients compared to control individuals with no significant difference in Ig ?/Ig ? ratios or heavy chain levels. Our study supports previous findings suggesting that KC possesses a systemic component that may contribute to the KC pathology. Further studies are required to define causality and establish a role for systemic immune system-dependent factors and pro-inflammatory processes in KC development or progression.

SUBMITTER: McKay TB

PROVIDER: S-EPMC7287105 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

McKay Tina B TB Serjersen Henrik H Hjortdal Jesper J Zieske James D JD Karamichos Dimitrios D

Scientific reports 20200610 1

Keratoconus (KC) is classically considered a non-inflammatory condition caused by central corneal thinning that leads to astigmatism and reduced visual acuity. Previous studies have identified increased systemic levels of pro-inflammatory factors, including interleukin-6, tumor necrosis factor-α, and matrix metalloproteinase-9, suggesting that KC may have an inflammatory component in at least a subset of patients. In this study, we evaluated the levels of different immunoglobulins (light and hea ...[more]

PMID: 32523038

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Project description:PurposeKeratoconus (KC) is a corneal ectasia characterized by structural changes, resulting in progressive thinning and biomechanical weakening that can lead to worsening visual acuity due to irregular astigmatism. Corneal collagen Crosslinking (CXL) and Intracorneal Ring Segment (ICRS) are widely used treatments in KC disease, but the alterations they cause in biomechanical mediators are still poorly understood. The aim of this study was to analyze the tear proteome profile before and after treatments to identify biomarkers altered by surgery.Materials and methodsAn observational, prospective, case-control pilot study was conducted, analyzing tear samples from KC patients by nano-liquid chromatography-mass spectrometry (nLC-MS/MS). Data are available via ProteomeXchange with identifier PXD035655. Patients with KC who underwent ICRS surgery (n = 4), CXL (n = 4), and healthy subjects (Ctrl, n = 4) were included in this study. Clinical parameters were measured and tear samples were collected before and 18 months after surgery. Proteins with ≥2 expression change and p-value < 0.05 between groups and times were selected to study their role in post-operative corneal changes.ResultsThese analyses led to the identification of 447 tear proteins, some of which were dysregulated in KC patients. In comparisons between the two surgical groups and Ctrls, the biological processes that were altered in KC patients at baseline were those that were dysregulated as a consequence of the disease and not of the surgical intervention. Among the biological processes seen to be altered were: immune responses, cytoskeleton components, protein synthesis and metabolic reactions. When comparing the two treatment groups (ICRS and CXL), the process related to cytoskeleton components was the most altered, probably due to corneal thinning which was more pronounced in patients undergoing CXL.ConclusionThe changes observed in tears after 18 months post-operatively could be due to the treatments performed and the pathology. Among the deregulated proteins detected, A-kinase anchor protein 13 (AKAP-13) deserves special attention for its involvement in corneal thinning, and for its strong overexpression in the tears of patients with more active KC and faster disease progression. However, it should be kept in mind that this is a pilot study conducted in a small number of patients.

Dataset Information

Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

Publications

Characterization of Tear Immunoglobulins in a Small-Cohort of Keratoconus Patients.

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