Circulating leukocyte alterations and the development/progression of diabetic retinopathy in type 1 diabetic patients - a pilot study

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 = .0152); reduced proportions of lymphocytes (p = .0002), HLA-DR⁺ leukocytes (p = .0406) and non-classical monocytes (p = .0204); and reduced expression of CD66a (p = .0048) and CD157 (p = .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 = .002) and increased neutrophil/CD8⁺ ratio (p = .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.