Investigating the role of the PD-1/PD-L1 pathway in cutaneous lupus erythematosus
Király Zsófia
KÁROLY RÁCZ CONSERVATIVE MEDICINE PROGRAM
Dr. Reusz György
SE Bőrgyógyászati Klinika
2024-06-19 11:00:00
Dermatology and Venereology
Dr. Sárdy Miklós
Dr. Hidvégi Bernadett
Dr. Bodó Imre
Dr. Gáspár Krisztián
Dr. Káldi Krisztina
Dr. Lakatos Bálint
Dr. Baltás Eszter
The various clinical presentations of CLE are well-recognized in clinical practice. However, finding an accurate diagnosis can be challenging in many cases, and the resistance of skin symptoms to therapy adds to the burden of CLE. The clinical presentation, development of systemic symptoms, and disease course differ between the two primary forms of CLE, namely, SCLE and a chronic form, DLE. Another important distinction between the two forms is that PD-1/PD-L1 inhibitor therapy can induce SCLE, which is unusual in the case of DLE. Based on this clinical observation, the possibility of different involvement of the PD-1/PD-L1 pathway in DLE and SCLE was raised.
In our pioneering studies, we investigated the PD-1/PD-L1 axis in CLE. First, CLE skin samples were analyzed by immunohistochemistry. A markedly lower KC PD-L1 expression was found in DLE compared to SCLE, while the number of PD-1+ lymphocytes was greater in DLE than in SCLE. In this study, no notable differences were found between non-PD1-SCLE and PD1-SCLE. In an alternative approach, the soluble forms of PD-1 and PD-L1 were investigated in individuals with CLE and some cases of SLE. The study revealed a significant increase in sPD-1 levels in SLE compared to DLE, SCLE, and HC groups. Additionally, the analysis found a significantly lower serum level of sPD-L1 in the DLE group compared to SLE, SCLE, and HC groups, with no significant differences observed in other comparisons.
Drawing upon our findings and existing literature, it appears plausible that the PD-1/PD-L1 pathway undergoes modulation in CLE. Nevertheless, it is important to note that the involvement of this pathway may exhibit distinct variations between DLE and SCLE. In our studies, the PD-L1 and sPD-L1 were both lower in DLE than in SCLE. According to this, it might be plausible that the inadequate inhibitory effect of PD-L1 and sPD-L1 on T-cell activity could promote the chronic form of CLE. These subtle differences might explain the variances of clinical presentations of DLE and SCLE.
