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Tissue Levels of MMP-9 and Granzyme B in Patients With Bullous Pemphigoid: A Case-Control Study
Hoa Dinh Pham1,2, Doanh Huu Le1,2, Tung Son Tran1,2
1Department of Dermatology, Hanoi Medical University, Ton That Tung, Hanoi, Vietnam.
Background:
Proteolytic enzymes, including matrix metalloproteinase-9 (MMP-9) and granzyme B, contribute to dermal-epidermal separation, but their expression in human skin lesions is not fully quantified. We aimed to quantify tissue levels of MMP-9 and granzyme B in bullous pemphigoid (BP) lesional skin compared to healthy controls.
Methods:
In a case-control study at the National Hospital of Dermatology and Venereology in Hanoi, Vietnam, between June 2024 and June 2025, lesional skin from BP patients and normal skin from healthy controls were analyzed. Matrix metalloproteinase-9 (MMP-9) and granzyme B levels were quantified using enzyme-linked immunosorbent assay (ELISA). Mann-Whitney U tests, linear regression, and receiver operating characteristic (ROC) analyses were conducted to assess group differences, clinical associations, and diagnostic performance.
Results:
Forty-eight BP patients and 21 healthy controls were included in our study. The median level of MMP-9 was 216.4 pg/mL/mg (interquartile range [IQR]: 74.6-570.0) in BP patients vs. 58.7 pg/mL/mg (IQR: 16.6-154.2) in controls (p = 0.0031). Granzyme B level was 2.16 pg/mL/mg (IQR: 1.26-5.13) in BP patients compared to 0.40 pg/mL/mg (IQR: 0.19-1.67) in the control group (p < 0.0001). ROC analysis showed areas under the curve (AUCs) of 0.722 for MMP-9 and 0.781 for granzyme B, while the combined model reached 0.799. MMP-9 level was correlated with body weight (r = 0.32, p = 0.023) and leukocyte counts (r = 0.29, p = 0.037), whereas granzyme B level was correlated with disease duration (r = 0.30, p = 0.032).
Conclusions:
Our study underscores that tissue levels of MMP-9 and granzyme B are significantly heightened compared to healthy controls. These proteases play a pivotal role in all types of skin lesions and reflect the local activity of BP.
Insights
Tissue levels of matrix metalloproteinase-9 (MMP-9) and granzyme B are significantly elevated in bullous pemphigoid (BP) skin lesions compared to healthy controls. These proteases are key factors in skin lesion activity and development.
Area of Science:
- Dermatology and immunology
- Protease research
- Skin pathology
Background:
- Proteolytic enzymes like matrix metalloproteinase-9 (MMP-9) and granzyme B are implicated in dermal-epidermal separation.
- Quantification of MMP-9 and granzyme B expression in human skin lesions, specifically bullous pemphigoid (BP), is limited.
Purpose of the Study:
- To quantify and compare tissue levels of MMP-9 and granzyme B in lesional skin of bullous pemphigoid patients versus healthy controls.
- To investigate the diagnostic performance of these proteases in BP.
- To explore correlations between protease levels and clinical parameters.
Main Methods:
- A case-control study was conducted with 48 BP patients and 21 healthy controls.
- Tissue levels of MMP-9 and granzyme B were measured using enzyme-linked immunosorbent assay (ELISA).
- Statistical analyses included Mann-Whitney U tests, linear regression, and receiver operating characteristic (ROC) analyses.
Main Results:
- Significantly higher median levels of MMP-9 (216.4 pg/mL/mg vs. 58.7 pg/mL/mg) and granzyme B (2.16 pg/mL/mg vs. 0.40 pg/mL/mg) were found in BP patients compared to controls (p < 0.0031 and p < 0.0001, respectively).
- ROC analysis indicated diagnostic potential with areas under the curve (AUCs) of 0.722 for MMP-9, 0.781 for granzyme B, and 0.799 for the combined model.
- MMP-9 correlated with body weight and leukocyte count, while granzyme B correlated with disease duration.
Conclusions:
- Tissue levels of MMP-9 and granzyme B are significantly elevated in bullous pemphigoid skin lesions.
- These proteases play a crucial role in the pathogenesis of skin lesions and reflect local disease activity in BP.
