Rasha N Yousef1, Abeer Ramadan2, Eman Awadallah1, Alshaimaa R Alnaggar3, Noha M Khalil3, Mervat E.Behiry3, Asmaa Ali4, Hesham Gamal El Dine1

1Department of Clinical and Chemical Pathology, National Research Centre, Giza, Egypt
2Department of Molecular Genetics & Enzymology, National Research Centre, Giza, Egypt
3Department of Internal Medicine, Rheumatology and Clinical Immunology Unit, Kasr Alainy School of Medicine, Cairo University, Cairo, Egypt
4Department of Chest Disease, Abbassia Chest Hospital, Ministry of Health and Population, Cairo, Egypt

Keywords: Apoptosis, bad, bax, flare, systemic lupus erythematosus.

Abstract

Objectives: In this study, we aimed to better understand the expression of pro-apoptotic Bad and Bax in the pathogenesis of systemic lupus erythematosus (SLE) and their relationship with the disease activity.

Patients and methods: Between June 2019 and January 2021, a total of 60 female patients with SLE (median age 29 years; IQR, 25.0-32.0) and 60 age- and sex-matched healthy female controls (median age: 30 years; IQR, 24.0-32.0) were included. The Bax and Bad messenger ribonucleic acid (mRNA) expression was measured by real-time polymerase chain reaction.

Results: The expression of Bax and Bad was significantly lower in SLE group than the control group. The median value of mRNA expression of Bax and Bad was 0.72 and 0.84, respectively versus 0.76 and 0.89 in the control group. The median value of (Bax*Bad)/β-actin index was 17.8 in the SLE group and 19.64 in the control group. The expression of both Bax, Bad and (Bax*Bad)/β-actin index had a good significant diagnostic utility (area under the curve [AUC]= 0.64, 0.70, and 0.65, respectively). The Bax mRNA expression showed a significant upregulation with disease flare-up. The efficacy of Bax mRNA expression in predicting SLE flare-up was good (AUC= 73%). In the regression model, the probability of flare-up reached 100%, with increasing Bax/β-actin as well, and the likelihood of flare-up increased 10,314 times with every unit increase of Bax/β-actin mRNA expression.

Conclusion: Deregulation of the mRNA expression of Bax may have a role in the susceptibility to SLE and may be associated with disease flare. A better understanding of the expression of these pro-apoptotic molecules may carry a great potential for the development of specific effective therapies.

Citation: Yousef RN, Ramadan A, Awadallah E, Alnaggar AR, Khalil NM, Behiry ME, et al. Pro-apoptotic Bax mRNA expression: A novel predictor for systemic lupus erythematosus disease flare-up. Arch Rheumatol 2023;38(1):129-137

Ethics Committee Approval

The protocol of the study was approved by ethics committee of the National Research Centre (date/no: January 2018/16385). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Author Contributions

Made the study design, supervised the project, participated in the molecular genetic studies, wrote the manuscript, and submitted the manuscript: R.N.Y.; Participated in the molecular genetic studies, participated in sample collection, data collection and analysis; A.R., E.A.; Collected samples and data of SLE patients and control subjects: A.R.A., N.M.K., M.E.B.; Made the statistics and analyzed the results; A.A.; Participated in molecular genetic studies, made study design, supervised the work and analyzed data, this manuscript was revised and approved by all authorm: H.G.E.D.

Conflict of Interest

The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.

Financial Disclosure

This work was supported by the National Research Centre, Egypt through a project (number of the project was 11010120).

Acknowledgments

I acknowledge the generous financial support from the National Research Centre, Egypt through a project (number of the project was 11010120).