Vitiligo is an autoimmune disease mainly caused by the destruction of melanocytes, leading to progressively enlarging white or hypopigmented patches on the skin. This not only affects appearance but may also cause psychological stress, and it is often comorbid with other autoimmune diseases such as thyroid disease and type 1 diabetes. Clinically, the most common form is non-segmental vitiligo, in which lesions are usually distributed symmetrically on both sides of the body. From a molecular and immunological perspective, vitiligo is mainly mediated by CD8+ T cells targeting melanocyte antigens. These cells secrete interferon-gamma (IFN-γ), which further damages melanocytes, leading to pigment loss and lesion expansion.

Research Directions
Based on this pathogenic mechanism, in our 2022 study, we investigated patients with vitiligo and healthy controls by combining multiplex cytokine analysis of skin blister fluid and plasma (Ng, Front Immunol, 2022) to identify biomarkers that could reflect disease activity, severity, and prognosis. The results showed that IFN-γ and its related signaling molecules CXCL9, CXCL10, and Granzyme B were significantly elevated in vitiligo lesions and plasma, whereas IL-1β, IL-13, IL-15, IL-17A, and IL-18 showed no significant differences. Among these markers, IFN-γ had the strongest ability to identify disease activity and predict treatment response, while CXCL9 better reflected disease severity. In addition, a decrease in IFN-γ after treatment was positively correlated with clinical improvement. Overall, this study supports the critical role of the IFN-γ axis and Granzyme B in the pathogenesis of vitiligo, and suggests that they have potential as objective biomarkers for clinical assessment and treatment monitoring.
Based on this clinical foundation, we infer that IFN-γ is a modifiable therapeutic target in patients with vitiligo. In another cohort of patients with mycobacterial infection, we successfully identified a monoclonal anti-interferon-gamma antibody and validated its high neutralizing activity against IFN-γ. This antibody has already been licensed to Anli Xiyo Biopharmaceutical Co., completed a Phase I clinical trial, and in March 2026, under the leadership of Dr. Chao-Yu Huang, Director of the Vitiligo Center at Linkou Chang Gung Memorial Hospital, has entered a Phase II clinical trial. At the same time, we plan to use full-spectrum flow cytometry to analyze the immune cell composition and status in patients in order to clarify their post-recovery immune responses. In addition, from the perspective of cell therapy, we are exploring possible treatments for vitiligo. Skin transplantation is currently one of the treatment options; however, based on this, we are now focusing on melanocyte regeneration therapy as a current research direction. The occurrence of vitiligo has also been observed in patients receiving cancer immunotherapy. Because immune checkpoint inhibitors can activate T-cell responses in multiple organs and tissues, they may trigger a series of autoimmune-related adverse events, known as immune-related adverse events (irAEs). Elucidating the molecular mechanisms behind this phenomenon is also a topic of interest to us.
Most of our experimental work is expected to start from clinical samples and be combined with several cell models for hypothesis validation. At the same time, we will establish a primary melanocyte culture system to better reflect disease characteristics, and we are also developing an ex vivo skin model to simulate skin composition and microenvironment, with the goal of translating these findings into clinical applications and the development of biologics.