Corneal confocal microscopy (CCM) has been used to identify corneal nerve damage and increased Langerhans cell (LC) density in adults with Type 1 diabetes mellitus (T1DM). The purpose of this study was to evaluate whether corneal confocal microscopy can identify early corneal nerve damage and change in LC density in children and adolescents with T1DM. 64 participants with T1DM (age-14.6 ± 2.5 years, duration of diabetes-9.1 ± 2.7 years, HbA1c-75.66 ± 2.53 mmol/mol [9.1 ± 1.8%]) and 48 age-matched healthy control subjects underwent CCM. Sub-basal corneal nerve morphology and the density of mature and immature LCs was quantified. Corneal nerve fibre length and branch density were lower, whilst fibre density and tortuosity did not differ and both immature and mature LC density was significantly higher in T1DM compared to control subjects. There was no association between HbA1c and duration of diabetes with nerve fibre parameters or LC’s density. Children and adolescents with T1DM demonstrate early immune activation and nerve degeneration.

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Background Neutrophils have been shown to contribute to the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful, and debilitating inflammatory skin disease, yet their exact role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF), a major regulator of neutrophil development and survival, can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. Objectives We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324. Methods Biopsy and peripheral blood samples were taken from participants of 2 studies: 2018.206, a non-interventional research study of systemic and dermal neutrophils and inflammatory markers in patients with neutrophilic skin diseases; and CSL324_1001 (ACTRN12616000846426), a single dose ascending and repeated dose, randomised, double-blind, placebo-controlled study to assess the safety, pharmacokinetics and pharmacodynamics of CSL324 in healthy adult subjects. Ex vivo experiments were performed, including neutrophil enumeration and immunophenotyping, migration, receptor occupancy and transcriptome analysis. Results The number of cells positive for the neutrophil markers myeloperoxidase (MPO) and neutrophil elastase (NE) was significantly higher in HS lesions compared with biopsies from healthy donors (HD) (p < 0.0001 and p = 0.0223, respectively). In peripheral blood samples, mean neutrophil counts were significantly higher in patients with HS than HD (2.98 versus 1.60 × 109/L, respectively; p = 8.8 × 10−4). Neutrophil migration pathways in peripheral blood were increased in patients with HS and their neutrophils demonstrated an increased migration phenotype, with higher mean CXCR1 on the surface of neutrophils in patients with HS (24453.20 versus 20798.47 for HD; p = 0.03). G-CSF was a key driver of the transcriptomic changes in the peripheral blood of patients with HS and was elevated in serum from patients with HS compared with HD (mean 6.61 versus 3.84 pg/mL, respectively; p = 0.013). Administration of CSL324 inhibited G-CSF-induced similar transcriptional changes in HD to those observed in the HS cohort, as highlighted by expression changes in genes related to neutrophil migratory capacity. Conclusions Data suggest neutrophils contribute to HS pathophysiology and that neutrophils are increased in lesions due to an increase in G-CSF-driven migration. CSL324 counteracted G-CSF-induced transcriptomic changes and blocked neutrophil migration by reducing cell surface levels of chemokine receptors.