Posted February 3, 2023

Victoria Werth, Ph.D., Philadelphia Research and Education Foundation

The body’s level of response has become a significant determining factor in the efficacy of certain antimalarial drugs in the treatment of cutaneous lupus erythematosus (CLE). For patients who are diagnosed with CLE, antimalarials, such as hydroxychloroquine (HCQ) and quinacrine (QC), are the first line of therapy; however, only half of patients respond to these therapies, and it takes at least two months before patients see any benefit.¹ During this two-month window, CLE continues to be active and, particularly in non-responders of antimalarial drugs, causes more inflammation, progressive visible tissue scarring, and other effects on the skin, such as hyperpigmentation. The two-month waiting period in monitoring a response to antimalarial drugs is too significant of a time delay in identifying these non-responders.

Dr. Victoria Werth and her team collected preliminary data to understand the biological determinants in patients recently diagnosed with CLE and to address uncharacterized responses to antimalarial treatment. With the funding awarded from a fiscal year 2019 Lupus Research Program Concept Award, Dr. Werth’s team tested the hypothesis that patients who were non-responsive to antimalarials would have uniquely expressed cell subtypes. Furthermore, their research aimed to illustrate the development of CLE and its response to therapy through the examination of 35 cellular and pathway markers in the skin of affected CLE patients.

The study population consisted of 40 patients with lesional CLE skin well-characterized at the beginning of the study (20 antimalarial responders and 20 antimalarial non-responders). Biopsies were collected and analyzed with two panels, containing 39 antibodies each, to assess cell-type and cellular pathways present in the samples. Through this method, the team was able to produce a visual picture of the cell clusters. The team found nine unique populations of immune cell types and analyzed the number of each cell type within the three responder groups (HCQ, HCQ+QC, antimalarial refractory). Samples within the antimalarial refractory group (non-responders) were found to have more CD8 T cells and CD20 B cells but had fewer T regs than samples that responded to QC. The team also confirmed that levels of conventional dendritic cells were more prevalent in HCQ+QC responders. Combined, these results demonstrate that patients that respond to antimalarials have different ratios of immune cells expressed.

Dr. Werth’s ultimate goal is to predict the patient’s response level and time-to-drug treatment. Using the data from the skin cells, the research team will be able to determine the practicality of a specific therapy for an individual by using the identified cell types to predict the patient’s response. Understanding the interaction between skin cells and pathways opens the door to a more individualized approach to targeted therapy in refractory disease. If successful, this work has the potential to provide patients with a reduction in the delay of treatment response, thereby helping to decrease skin scarring and disease activity and, ultimately, increase CLE patient quality of life.

References:
¹Harada M, Morimoto K, Kondo T, et al. 2017. Quinacrine inhibits ICAM-1 transcription by blocking DNA binding of the NF-κB subunit p65 and sensitizes human lung adenocarcinoma A549 cells to TNF-α and the fas ligand. International Journal of Molecular Science 18(12):2603. Published online 2017 Dec 2. doi: 10.3390/ijms18122603 PMCID: PMC5751206 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751206/.

Links:
Public and Technical Abstracts: Immunologic Mechanisms for Heterogeneity of Cutaneous Lupus Erythematosus

Top of Page

Last updated Friday, February 3, 2023