Clinical Characteristics and Possible Mechanisms of Age Differences in Bullous Pemphigoid (BP) Patients

Academic Background

Bullous Pemphigoid (BP) is an acquired autoimmune blistering disease that primarily affects elderly patients. However, in recent years, the incidence of BP among younger individuals has also increased, with younger patients often experiencing more severe conditions and greater treatment challenges. Although the pathogenesis of BP has been studied to some extent, research on the clinical characteristic differences among patients of different ages and their underlying mechanisms remains limited. To better understand the manifestations of BP in patients of various age groups and provide more effective treatment options for younger patients, the authors conducted this study. The research aims to analyze the clinical characteristic differences among BP patients of different ages and explore the potential mechanisms behind these differences.

Source of the Paper

This study was conducted by Xinyi Chen, Bingjie Zhang, Xuming Mao, and other scholars, primarily from the Department of Dermatology at Peking Union Medical College Hospital and the University of Pennsylvania, among other institutions. The paper was published in the Journal of Dermatology in 2025, with the DOI: 10.¹¹¹¹⁄₁₃₄₆-8138.17616.

Research Process

Study Subjects and Data Collection

The study included 215 BP patients who visited the Department of Dermatology at Peking Union Medical College Hospital between January 2009 and September 2020. The patients were divided into five groups based on age at onset: <50 years, 50-59 years, 60-69 years, 70-79 years, and ≥80 years. Clinical data were collected through medical records and telephone follow-ups, analyzing anti-BP180 antibody subclasses, anti-BP230 antibodies, complement fixation, serum cytokine levels, and single nucleotide polymorphisms (SNPs).

Experimental Methods

1. Immunoglobulin Subclass Analysis: Commercially available ELISA kits were used to detect IgG1, IgG4, and IgE subclasses of anti-BP180 and anti-BP230 antibodies in patient sera. The sera were stored at -80°C, diluted, and incubated with mouse anti-human IgG1, IgG4, and IgE antibodies. Antibody levels were determined by measuring optical density (OD) values.

2. Complement Fixation Test (CFT): Monkey esophagus sections were incubated with patient sera, combined with complement and fluorescence-labeled anti-C3 antibodies, to observe linear C3 deposition at the basement membrane and assess complement activation capacity.

3. Serum Cytokine Analysis: ELISA kits were used to measure serum levels of cytokines, including IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, TNF-α, IFN-γ, and TGF-β1.

4. Single Nucleotide Polymorphism (SNP) Detection: Genomic DNA was extracted from whole blood, and SNPs in cytokine genes, including IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-13, TNF-α, IFN-γ, and TGF-β1, were analyzed using the MassArray system.

Main Results

Clinical Characteristic Analysis

The study found that BP patients under 60 years old were more likely to be misdiagnosed upon their first visit, particularly those under 50 years old, with 51.9% misdiagnosed as eczema or other skin diseases. Younger patients had a significantly higher rate of oral mucosal involvement than older patients (33.9% vs. 19.2%), and their anti-BP180 IgE antibody levels and C3 deposition rates were also significantly elevated (P=0.044 and P=0.014, respectively), while anti-BP230 IgG antibody levels were lower (P=0.043). Additionally, the hospitalization rate for patients under 50 was significantly higher than for those over 80 (P<0.001).

Serum Cytokine Levels

Patients under 60 had significantly higher serum concentrations of IL-13, TNF-α, and IFN-γ compared to other age groups (P<0.005). This aligns with the clinical characteristics of more severe conditions and greater treatment challenges in younger patients.

Genotype Polymorphism Analysis

Significant differences in the distribution of genotypes or alleles were observed for TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705 among patients of different age groups. These genetic polymorphisms may be associated with early-onset BP and its severe manifestations in younger patients.

Conclusion

The study indicates that the age of onset in BP patients is closely associated with their clinical characteristics, immunological factors, and prognosis. Younger patients are more prone to misdiagnosis, oral mucosal involvement, higher anti-BP180 IgE antibody levels, C3 deposition rates, and elevated levels of cytokines such as IL-13, TNF-α, and IFN-γ. In contrast, elderly patients are more likely to have neurological diseases and higher peripheral blood eosinophil counts. Gene mutations in TNF-α rs1799964, TNF-α rs1800630, and IFN-γ rs2069705 may be related to early-onset BP in younger patients. These findings provide new insights into the pathogenesis of BP in patients of different ages and offer valuable references for the diagnosis and treatment of younger patients.

Research Highlights

1. Cross-Age Clinical Characteristic Differences: The study systematically analyzed the clinical characteristic differences in BP patients across different age groups, revealing that younger patients tend to have more severe conditions, higher misdiagnosis rates, and greater treatment challenges.

2. Exploration of Immunological Mechanisms: By analyzing antibody subclasses, complement activation, and cytokine levels, the study unveiled the potential immunological mechanisms behind the severe conditions in younger patients.

3. Association with Genetic Polymorphisms: For the first time, the study identified associations between TNF-α and IFN-γ genetic polymorphisms and early-onset BP in younger patients, providing new clues for genetic research in BP.

Value and Significance

This study not only enriches the understanding of BP pathogenesis but also offers significant clinical references for the diagnosis and treatment of younger patients. By revealing the characteristic differences and underlying mechanisms among BP patients of different ages, the research provides a scientific basis for developing personalized treatment plans, holding substantial clinical application value.