Interleukin 38 serum level is increased in patients with vitiligo, correlated with disease severity, and associated with signs of disease activity

Abstract

Background Vitiligo is an acquired cutaneous depigmenting disease caused by a T helper (Th) 1–cytotoxic T cells driven autoimmune attack against melanocytes, in which Th17 is also involved. Interleukin (IL)‐38 belongs to the IL‐1 family of cytokines and suppresses Th1 and Th17 activation. IL‐38 protein and mRNA levels have been found to be elevated in various autoimmune disorders and correlated with disease severity and activity, including psoriasis, systemic sclerosis, rheumatoid arthritis, and atopic dermatitis. No previous studies have been performed to investigate the expression of IL‐38 in patients with vitiligo. Aim To evaluate IL‐38 serum level in patients with vitiligo compared to healthy controls (Hcs) and examine the association between IL‐38 level and severity and activity of vitiligo. Patients and Methods The study comprised 21 patients with vitiligo and 21 Hcs. Vitiligo severity and activity were evaluated via Vitiligo Extent Score (VES) and Vitiligo Disease Activity (VIDA) Score, respectively. IL‐38 serum level was evaluated by enzyme‐linked immunosorbent assay. Results Vitiligo patients had significantly higher serum level of IL‐38 than Hcs (p < 0.001). This level was significantly higher among patients with signs of vitiligo activity (p = 0.048), correlated positively with VES (p < 0.001), and correlated negatively with the age of patients (p = 0.001) and the age of disease onset (p = 0.022). Conclusion IL‐38 serum level was higher in patients with vitiligo than in Hcs and was related to vitiligo severity and signs of activity.

Circulating interleukin-38 concentrations in healthy adults

“…BMI shows a trend towards higher BMI corresponding with lower IL-38 concentrations ( Figure 3D ), as was observed before ( 28 ). Also, age shows an inverse correlation with IL-38 concentrations ( Figure 3E ), which also corresponds with previously published data ( 28 , 43 ). Lastly, we determined whether IL-38 remains stable over time in two cohorts for which multiple consecutive samples were available.…”

“…Age showed a negative correlation with IL-38 concentrations, and in BMI a (although not significant) negative trend was observed. These observations were also comparable with prior studies ( 28 , 41 , 43 ). Lastly, no major variation over longer time courses was observed, which had also been shown before in 48 subjects over a time period of a year ( 28 ).…”

“…IL-38 is the latest added member of the IL-1 family of cytokines, but in the last few years it has already been shown to be dysregulated in a wide range of diseases such as cancer, infectious diseases, and autoimmunity ( 6 , 7 ). Patients with atopic dermatitis ( 20 ), influenza ( 21 ), SLE ( 22 ), rheumatoid arthritis ( 25 , 39 ), myocardial infarction ( 23 ), sepsis ( 24 ), acquired immune-mediated neuropathies ( 31 ), osteoarthritis ( 32 ), acute respiratory distress syndrome ( 35 ), inflammatory bowel disease ( 33 ), type 2 diabetes ( 41 ), and vitiligo ( 43 ) present with higher blood concentrations of IL-38. This in contrast to e.g., patients with Graves’ and Hashimoto’s thyroiditis ( 44 ), Sjögren’s disease ( 34 ), Behçet’s disease ( 37 ), chronic brucellosis ( 40 ), and psoriasis ( 27 ), in whom IL-38 circulating concentrations were lower compared to healthy volunteers.…”

“…The distribution curve presented in Figure 3B shows that most subjects have IL-38 concentrations around the lower limit of detection. It is therefore imaginable that studies reporting very low mean concentrations ( 33 , 43 ) might report background noise as IL-38 values. This suggests that a more sensitive ELISA that could determine even lower concentrations of IL-38 could generate a more reliable image of the distribution of IL-38 in healthy adults.…”

Evaluation of IL-38, a Newly-Introduced Cytokine, in Sera of Vitiligo Patients and Its Relation to Clinical Features

“…Moreover, an association of IL-38 rs7570267 and rs3811058 single nucleotide polymorphism with RA susceptibility has been shown [ 18 ]. In another study on RA patients, elevated levels of IL-38 was reported in plasma of patients compared to healthy controls [ 28 ]. Rudloff et al measured the IL-38 serum level in patients with SLE.…”