Circulating Leukocyte Alterations and the Development/Progression of Diabetic Retinopathy in Type 1 Diabetic Patients – A Pilot Study

Gideon Obasanmi, Noemi Lois, David Armstrong, Nuala Jane Lavery, Jose M Romero Hombrebueno, Aisling Lynch, David Wright, Mei Chen, Heping Xu

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Abstract

Background/Aims: The aim of this study was to investigate the relationship between alterations in circulating leukocytes and the initiation and progression of DR in people with type 1 diabetes (T1D).

Methods: Forty-one patients with T1D [13 mild non-proliferative DR (mNPDR), 14 active proliferative DR (aPDR) and 14 inactive PDR (iPDR)], and 13 age- and gender-matched healthy controls were recruited prospectively. Circulating leukocytes, including CD4+ and CD8+ T-cells, CD14+CD16-, CD14-CD16+ and CD14+CD16+ monocytes; CD16+HLA-DR- neutrophils, CD19+ B-cells and CD56+ natural killer cells and their cell surface adhesion molecules and chemokine receptors (HLA-DR, CD62L, CCR2, CCR5, CD66a, CD157 and CD305) were examined by flow cytometry.

Results: In DR patients, compared to healthy controls, increased proportions of neutrophils (p=0.0152); reduced proportions of lymphocytes (p=0.0002), HLA-DR+ leukocytes (p=0.0406) and non-classical monocytes (p=0.0204); and reduced expression of CD66a (p=0.0048) and CD157 (p=0.0007) on CD4+ T cells were observed. Compared to healthy controls, CD19+ B cells were reduced at the mNPDR but not aPDR patients. Total lymphocytes, CD4+ T cells and CD8+ T cells progressively decreased whereas neutrophils, the neutrophil/lymphocyte ratio and the neutrophil/CD4+ ratio progressively increased from early to late stages of DR, reaching statistical significance at the aPDR stage. Longer diabetes duration was associated with a reduced proportion of CD8+ T cells (p=0.002) and increased neutrophil/CD8+ ratio (p=0.033).

Conclusions: In this pilot study, DR is associated with increased innate cellular immunity especially neutrophils and reduced adaptive cellular immunity particularly lymphocytes. Impaired B-cell immunity may play a role in the initiation of DR; whereas impaired T-cell immunity with increased neutrophil response may contribute to progression of DR from non-proliferative to proliferative stages in T1D patients. Large multicenter studies are needed to further understand the immune dysregulation in DR initiation and progression.
Original languageEnglish
Number of pages11
JournalCurrent eye research
Early online date30 Jan 2020
DOIs
Publication statusEarly online date - 30 Jan 2020

Keywords

  • type 1 diabetes
  • diabetic retinopathy
  • neutrophils
  • lymphocytes
  • flow cytometry

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