In vitro evaluation of the potential immunosuppressive effect of panobinostat on cultured lymphocytes retrieved from childhood systemic lupus erythematosus patients

The Egyptian Journal of Immunology
Volume 30 (4), October, 2023
Pages: 145 – 154.
www.Ejimmunology.org
https://doi.org/10.55133/eji.300415
Neimat A. Yassin1, Maha Abdelsalam2,3, Amr M. El-Sabbagh4, Amira I. Morsy5, Amira A. Haleem6, Ibrahim El-Shenbaby1, Gehan A. El Wakeel7, Ayman Hammad8, Nashwa Hamdy8, Dena M. Abd-El Ghafaar9, Eman B. Elmarghany9, Mai S. Korkor8, and Riham Eid8
1Department of Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

2Immunology Unit, Department of Clinical Pathology, Faculty of Medicine, Mansura University, Egypt.

3Laboratory Department, Faculty of Allied Health Science, Badr University, Cairo, Egypt.

4Department of Medical Microbiology & Immunology, Faculty of Medicine, Mansoura, University, Egypt.

5Department of Medical Anatomy, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

6Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

7Department of Medical Physiology, Faculty of Medicine, Mansoura University, Egypt.

8Pediatric Nephrology Unit, Mansoura University Children’s Hospital, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

9Department of Rheumatology, Faculty of Medicine, Mansoura University, Egypt.

Corresponding author:
Neimat A. Yassin, Department of Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Email: yassinneimat@gmail.com.

 

Abstract

Although many drugs are available for childhood systemic lupus erythematosus (SLE) treatment, the adverse effects and poor response in some cases make it crucial to find new drugs targeting various pathways in disease pathogenesis to improve overall outcomes. This study aimed to (i) investigate the effect of Panobinostat on cultured lymphocytes obtained from children with active SLE and (ii) to compare that effect with standard drugs used in SLE, such as Prednisone and hydroxychloroquine. The study included 24 SLE active patients, divided into four equal groups. Lymphocytes were isolated from blood samples of the study patients. According to the study group, cells were treated with either Panobinostat, Prednisolone, hydroxychloroquine, or not treated (control group). After cell culture, the response of lymphocytes upon drug treatment was analyzed in terms of the production of anti-dsDNA antibodies and levels of apoptosis as detected by flow cytometry using annexin V and propidium iodide (PI) staining. The Panobinostat group showed a significant decrease in the viable cell count (p<0.001). Both Prednisone and hydroxychloroquine decreased anti-dsDNA expression more than the Panobinostat and control groups (p<0.001 for both). PI was higher in the Prednisone group, and Annexin V was higher in the Panobinostat group compared to other groups; however, their increase did not reach statistically significant levels (p= 0.12 and 0.85, respectively). This is the first study of the Panobinostat effect on cultured lymphocytes of SLE. In conclusion, Panobinostat could be a prospective treatment for B-cell-driven autoimmune diseases such as SLE. However, its effect on autoantibodies levels and different clinical features of SLE still need a thorough evaluation.

Keywords:
SLE, cultured lymphocytes, Panobinostat.

Date received:
10 October 2022; accepted: 19 September 2023

PMID:
37801033

 

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