T lymphocyte and monocyte subsets are dysregulated in type 1 diabetes patients with peripheral neuropathic pain

Jayden A O'Brien; Helen M McGuire; Diana Shinko; Barbara Fazekas de St Groth; Marc A Russo; Dominic Bailey; Danielle M Santarelli; Katie Wynne; Paul J Austin

doi:10.1016/j.bbih.2021.100283

T lymphocyte and monocyte subsets are dysregulated in type 1 diabetes patients with peripheral neuropathic pain

Brain Behav Immun Health. 2021 Jun 9:15:100283. doi: 10.1016/j.bbih.2021.100283. eCollection 2021 Aug.

Authors

Jayden A O'Brien¹, Helen M McGuire^{2

3}, Diana Shinko^{3

4}, Barbara Fazekas de St Groth^{2

3}, Marc A Russo⁵, Dominic Bailey^{5

6}, Danielle M Santarelli⁵, Katie Wynne^{7

8}, Paul J Austin¹

Affiliations

¹ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Brain and Mind Centre, 94 Mallett St, Camperdown, NSW, 2050, Australia.
² Discipline of Pathology, Faculty of Medicine and Health, The University of Sydney, NSW, Australia.
³ Ramaciotti Facility for Human Systems Biology, Charles Perkins Centre, The University of Sydney, NSW, Australia.
⁴ Sydney Cytometry, The University of Sydney, NSW, Australia.
⁵ Genesis Research Services, Broadmeadow, NSW, Australia.
⁶ Hunter Medical Research Institute, New Lambton Heights, NSW, Australia.
⁷ Department of Diabetes and Endocrinology, John Hunter Hospital, Newcastle, NSW, Australia.
⁸ School of Medicine and Public Health, University of Newcastle, NSW, Australia.

Abstract

Diabetic neuropathic pain is a common and devastating complication of type 1 diabetes, but the mechanism by which it develops and persists is yet to be fully elucidated. This study utilised high-dimensional suspension mass cytometry in a pilot cohort to investigate differences in peripheral blood immunophenotypes between type 1 diabetes patients with (n = 9) and without (n = 9) peripheral neuropathic pain. The abundance and activation of several leukocyte subsets were investigated with unsupervised clustering approaches FlowSOM and SPADE, as well as by manual gating. Major findings included a proportional increase in CD4⁺ central memory T cells and an absolute increase in classical monocytes, non-classical monocytes, and mature natural killer cells in type 1 diabetes patients with pain compared to those without pain. The expression of CD27, CD127, and CD39 was upregulated on select T cell populations, and the phosphorylated form of pro-inflammatory transcription factor MK2 was upregulated across most populations. These results provide evidence that distinct immunological signatures are associated with painful neuropathy in type 1 diabetes patients. Further research may link these changes to mechanisms by which pain in type 1 diabetes is initiated and maintained, paving the way for much needed targeted treatments.

Keywords: CD27; Chronic pain; Diabetic neuropathy; FlowSOM; Immunophenotyping; MAPKAPK2; MK2; Mass cytometry; SPADE; Type 1 diabetes.