Tissue Levels of MMP‐9 and Granzyme B in Patients With Bullous Pemphigoid: A Case–Control Study

ABSTRACT 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.