New findings suggest that while serum interleukin (IL)-13 levels are lower in patients with bullous pemphigoid compared to healthy controls, suggesting IL-13 maintains a complex role in disease pathogenesis, IL-13 levels do not correlate with bullous pemphigoid severity or prognosis.1
Marwan Dawood, MD, from the Department of Dermatology at Rambam Health Care Campus in Israel, led a team of investigators who authored this analysis. Dawood et al highlighted that bullous pemphigoid is the most commonly seen autoimmune blistering disease, with prevalence that has reportedly risen in recent years.2
“Our study aimed to compare IL-13 levels between DPP4-induced [bullous pemphigoid] and non-triggered [bullous pemphigoid], as well as to compare these levels with those of healthy controls and pemphigus patients,” Dawood and colleagues wrote.1
Trial Design and Notable Findings
The investigative team’s retrospective cohort study involved an assessment of adult patients diagnosed with bullous pemphigoid between 2008 – 2023, specifically among those given a diagnosis at the dermatology department of Rambam Hospital in Haifa, Israel. Through a clinical evaluation alongside positive findings from direct immunofluorescence (DIF), specifically IgG deposition along the basement membrane, these diagnoses were confirmed. Those deemed as eligible participants were adults ≥18 years who also had a confirmed diagnosis shown to be supported by clinical, histopathological, and immunological evidence.
There were 12 healthy individuals and 4 patients with pemphigus vulgaris in the control arm of the analysis. Healthy controls were matched to subjects with bullous pemphigoid by sex and by age to diminish the possibility of demographic bias. Notably, the investigators found that none of those in the control arm had a personal history of autoimmune or inflammatory conditions.
Serum samples, after being obtained from all study participants at the time of diagnosis, frozen prior to the initiation of any BP-specific treatment at −80°C until additional analyses were required. IL-13 levels were quantified by Dawood and colleagues via a commercially available IL-13 ELISA kit, with measurements being done at a single time point rather than throughout treatment.
The primary aim of Dewad and coauthors’ assessment was to evaluate serum IL-13 concentrations and their relationship with etiology of bullous pemphigoid, with peripheral eosinophil counts, with the requirements for adjunctive treatment, and with mucosal involvement. Using electronic medical records, they collected clinical and laboratory data such as demographic characteristics, disease origin, treatment information, and results of patients’ blood tests.
Overall, the investigators concluded that mean serum IL-13 levels were significantly lower among those with bullous pemphigoid (n=42; mean 62.46 pg/mL ± 16.53) compared to healthy controls (n=12; mean 87.83 pg/mL ± 8.87, P < .0001) and compared to those with pemphigus vulgaris (n=4; mean 87.6 pg/mL ± 5.16, P = .013).1 Within the bullous pemphigoid subgroup, it was noted that subjects with idiopathic bullous pemphigoid showed higher IL-13 levels versus those with DPP4-inhibitor–associated bullous pemphigoid (67.01 pg/mL ± 14.3 vs. 57.36 pg/mL ± 21, P = .0104).
The team did not observe any statistically significant associations between IL-13 levels and eosinophil counts (Pearson’s r = .18, P = .253), mucosal involvement (P = .338), utilization of adjuvant therapy (P = .32), or patients’ disease prognosis (P = .45). However, they did find a significant link between elevated eosinophil counts and the need for adjuvant treatment (P = .027).
“This study highlights the significant variability in serum IL-13 levels among [bullous pemphigoid] patients, distinguishing idiopathic and DPP4i-induced [bullous pemphigoid],” the team concluded.1 “…With the emergence of anti-IL13 biologics, our findings emphasize the need for further research into IL-13’s role in [bullous pemphigoid] pathogenesis and treatment, towards the development of future personalized approaches in [bullous pemphigoid] management.”
References
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RL Colbert, DM Allen, D Eastwood, et al. “Mortality Rate of Bullous Pemphigoid in a US Medical Center,” Journal of Investigative Dermatology 122, no. 5 (2004): 1091–1095, https://doi.org/10.1111/j.0022-202X.2004.22504.x.
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Dawood M, Saleh ZA, Boyango I, et al. The Complex Role of IL-13 in Bullous Pemphigoid: New Insights From a Retrospective Cohort Study. JEADV Clinical Practice. https://doi.org/10.1002/jvc2.70018.