UAB researchers uncover that interaction between proteins CD2:CD58 can be disrupted to mitigate the expression of genes and proteins that trigger HS pathogenesis.Hidradenitis suppurativa, commonly referred to as HS, is a debilitating skin condition that causes chronic inflammation on the surface of the skin. This condition is characterized by painful bumps or boils that form under the skin and can sometimes rupture.
In a study published in Proceedings of the National Academy of Sciences, University of Alabama at Birmingham Department of Dermatology professors Chander Raman, Ph.D., and Mohammad Athar, Ph.D., and their research team revealed that, by disrupting the protein CD2’s interaction with CD58, the gene expressions that result in HS symptoms could be suppressed, resulting in potential novel treatment options for those impacted by HS.
Typically affecting skin-fold regions such as armpits, groin, buttocks, breasts and areas of high sweat production, HS commonly impacts the physical well-being of those afflicted and negatively impacts their social quality of life. Current treatments for HS mainly reduce some symptoms; but they do not cure or arrest the progression of the disease, and overall quality of life remains an issue unaddressed satisfactorily.
The Raman and Athar team’s study uncovered that the lymphocyte cell surface protein CD2 is expressed at elevated levels on T lymphocytes and innate lymphocytes, including natural killer cells (NK), natural killer T cells (NKT) and mucosal-associated invariant T cells (MAIT) in HS lesions. The understanding that innate lymphocyte populations, specifically NKT cells and natural killer cells, express high levels of CD2 and are the predominant lymphocyte population in HS lesions helped this study to demonstrate that the blockade of cognate interaction between CD2 and CD58 had profound effects in mitigating gene expression and secretion of proteins (cytokines, chemokines, growth factors) which are highly relevant to the pathogenesis of HS.
CD2 through its interaction with the cell surface protein, CD58, has critical functions for the activation of T cells and innate lymphocytes leading to the perpetuation of the inflammatory response, which remains poorly understood and is current focus of this group’s research.
“Our study identifies CD2:CD58 interaction along with NKT and NK cells as major drivers of HS pathogenesis,” Raman said. “Targeting of CD2:CD58 therapeutically offers an opportunity to treat HS, an incurable debilitating skin disease impacting quality of life among young patient populations, particularly women.”
According to the HS Foundation, HS impacts about 1 percent to 2 percent of people, particularly between the age group of 16-40, in the United States. The disease commonly affects women of African American descent.
“Defining the immune cell landscape of HS, particularly at different stages of the disease, and their molecular signatures along with interacting epithelial cell populations will provide us the tools to understand disease progression and develop therapies that arrest and potentially cure the disease,” Athar said.
This study included members of UAB Marnix E. Heersink School of Medicine Department of Dermatology and Department of Medicine, including Boni Elewski, M.D., and Craig Elmets, M.D. Mahendra Kashyap, Ph.D., is the first author of the study.
In collaboration with Shahid Mukhtar, Ph.D., and his team at Clemson University, a multi-omics analysis was performed during the duration of this study. This team included Bharat Mishra, Ph.D., who shares co-first authorship with Kashyap.
Erik Berglund, M.D., Ph.D., and David Berglund, M.D., Ph.D., co-founders of ITB-MED, developers of TCD601 (siplizumab), a humanized antagonistic CD2 monoclonal antibody, contributed to the study.