Comparative evaluation of cytokine profiles in pediatric alopecia areata patients considering concomitant atopic diseases: An observational cohort cross-sectional study

Background. Alopecia areata is an autoimmune disease affecting hair follicles that is frequently associated with atopic diseases. Studies on cytokine profiles in the context of atopic comorbidities help to identify the key immune mechanisms and specific immunophenotypes. The present study aims to identify immune differences in alopecia areata depending on the atopic status.

Objective. To assess the serum levels of the main proinflammatory and regulatory cytokines in patients with alopecia areata, taking the presence of atopic diseases and the severity of the process into account.

Methods. An observational cohort cross-sectional study was conducted at the Moscow Scientific and Practical Center of Dermatovenereology and Cosmetology of the Moscow City Health Department. The study included 44 alopecia areata patients aged 5–17 years, who were divided into two groups: 1) patients without atopy (n = 17); 2) patients with concomitant atopic diseases (n = 27). The severity of alopecia areata was graded using the Severity of Alopecia Tool (SALT). Cytokine concentration was studied via a multiplex assay (Luminex 200, ProcartaPlex Human Cytokine&Chemokine Panel 1A, 34plex). Of the 34 target parameters, granulocyte-macrophage colony-stimulating factor, interleukin-1β, and interleukin-15 were excluded from analysis due to the lack of detection in ≥20 participants. The remaining 31 parameters were compared between the groups and with the comparable healthy control group (n = 30). The correlation between the serum cytokine levels and alopecia severity was analyzed. The obtained data were statistically processed using Statistica 10.0 (StatSoft, USA) and Microsoft Excel 2016 (Microsoft Corporation, USA). The statistical significance level is α = 0.05. In order to estimate the correlation coefficient (r) and its statistical significance (p), Spearman’s coefficient was used. SCImagoGraphica software (SCImago LAB, Spain) was used for the graphic representation of the obtained results.

Results. Differences between Groups 1–2 and the control group were found for 18 cytokines. Group 2 patients (with atopy) exhibited differences from the control group (p < 0.005) in the distribution of levels of all Type 2 cytokines, Type 1 cytokines (interleukin-2, interleukin-12, and tumor necrosis factor alpha and beta), and T helper 17 cytokines (interleukins 21, 22, 23, and 27), except for interleukin-17A. In Group 1 (without atopy), interleukin-4, interleukin-9, and eotaxin levels did not differ from those in the control group, while the level of interleukin-17A was elevated (p = 0.007). A direct comparison of the distribution of cytokine levels showed no statistically significant differences between Groups 1 and 2 in any of the parameters. The correlation between cytokine levels in alopecia areata patients and the disease severity was analyzed in all patients without dividing them according to their atopic status due to the limited sample size in the subgroups. The levels of interleukins 1 alpha, 10, 21, 22, 23, 27 and tumor necrosis factor beta were positively correlated with alopecia severity, especially interleukin-23 (r = 0.372, p = 0.008); a negative correlation with SALT scores was observed for interleukin-2 (r = −0.457, p = 0.011) and interleukin-4 (r = −0.489, p = 0.006).

Conclusion. The obtained results confirm the complex and systemic nature of immune abnormalities in alopecia areata. T helper 2 cytokines are clearly involved in the pathophysiologic process, with comorbid atopic diseases enhancing the T helper 2 response, potentially modulating interleukin-17A expression. The severe course of alopecia is associated with the activation of T helper 17 mediators (except for interleukin-17A) and a decrease in the levels of interleukins 2 and 4. The obtained data justify the appropriateness of personalized therapy that takes the atopic status and cytokine profile into account.

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