Study Highlights Role of IL-33 in Link Between Asthma, Alopecia Areata

There is an association between asthma and alopecia areata, new findings suggest, suggesting a mediating role of interleukin (IL)-33 and emphasizing the value of considering alopecia areata risk in management of asthma.¹

These findings were the results of a new Mendelian randomization analysis—led by Pingfan Wu, from the department of plastic and aesthetic surgery at the the Second Affiliated Hospital of Soochow University in China—conducted to elucidate the causal association between alopecia areata and asthma.

The investigators noted that around 2% of the global population reports having the autoimmune disorder alopecia areata, adding that rates of the disease’s incidence are rising.² They also expressed that recent epidemiological research had consistently identified a link between asthma and alopecia.

“Our findings may elucidate causal pathways linking asthma and (alopecia areata), identifying interleukin-33…as a potential mediator,” Wu and colleagues wrote. “This discovery could pave the way for novel diagnostic biomarkers and innovative therapeutic targets.”¹

Trial Design

The investigators conducted a genome-wide association study (GWAS) for asthma, looking specifically at data drawn from the IEU Open GWAS database of 56,087 asthma cases and 428,511 control subjects of European ancestry. There were 91 circulating inflammatory proteins that the team highlighted, gathering their information through the Olink Target platform from research involving 14,824 Europeans.

The research team’s summary statistics for alopecia areata were collected using the FinnGen biobank. This database involved 682 cases and provided 361,140 control subjects.

For their exploration of the link between alopecia areata and asthma, the team implemented a Mendelian randomization (MR) analysis, using genetic instrumental variables (IVs) for asthma as well as the 91 aforementioned circulating inflammatory proteins. The inverse-variance weighted (IVW) method was the investigators’ major analytical approach.

They created additional evaluations through the use of the weighted median and MR-Egger methods, with the purpose being an assessment of the study’s robustness. The research team also carried out heterogeneity and pleiotropy tests, with their aim being the assurance of their data’s reliability.

Horizontal pleiotropy was identified by the investigators using a significant non-zero intercept in the MR-Egger regression (P < .05). They determined statistical significance using 2-tailed tests, considering p-values under .05 as significant.

Study Findings

Overall, the research team concluded that those with asthma had a significant risk increase in terms of alopecia areata development. The team noted the odds ratio (OR) of 14.070 (95% CI: 1.410–140.435; P = .024).

A key mediator of the connection between alopecia and asthma was IL-33, and the investigators reported that it accounted for 13.1% of the mediation effect. However, the bidirectional Mendelian randomization analyses did not support a causal link between alopecia and patients’ development of asthma.

One limitation of this study is its reliance on data from individuals of European ancestry, which may limit the applicability of the findings to more diverse populations. Future research should aim to include more diverse cohorts to validate and expand upon these findings. Despite employing sophisticated statistical methods to control for confounding factors, the study's observational design is another limitation that should be considered.

“Despite these limitations, our research represents a foundational step towards a deeper understanding of the interaction between asthma and (alopecia areata),” they wrote. “It offers valuable hypotheses for further exploration and underscores the importance of continued research in this area.”

References

1. ^{Wu P, Tian K, Gao S, et al. Interleukin-33 links asthma to alopecia areata: Mendelian randomization and mediation analysis. Skin Res Technol. 2024; 30:e13864. https://doi.org/10.1111/srt.13864.}
2. ^{Ly S, Manjaly P, Kamal K, et al. Comorbid conditions associated with alopecia areata: a systematic review and meta-analysis. Am J Clin Dermatol. (2023) 24(6): 875-893. doi:10.1007/s40257-023-00805-4.}