Superantigen influence in conjunction with cytokine polymorphism potentiates autoimmunity in systemic lupus erythematosu
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ORIGINAL ARTICLE
Superantigen influence in conjunction with cytokine polymorphism potentiates autoimmunity in systemic lupus erythematosus patients Sajad Ahmad Dar1,5 • Essam Mohammed Ahmed Janahi2 • Shafiul Haque3,5 • Naseem Akhter4 • Arshad Jawed5 • Mohd Wahid5 • Vishnampettai Ganapathysubramanian Ramachandran1 Sambit Nath Bhattacharya6 • Basu Dev Banerjee7 • Shukla Das1
•
Ó Springer Science+Business Media New York 2015
Abstract Risk posed by microbial superantigens in triggering or exacerbating SLE in genetically predisposed individuals, thereby altering the response to its treatment strategies, has not been studied. Using streptococcal pyrogenic exotoxin A and staphylococcal enterotoxin B as prototype superantigens, we have demonstrated that they profoundly affect the magnitude of polyclonal T cell response, particularly CD4? T cells and expression of CD45RA and CD45RO, and cytokine secretion in vitro in SLE patient PBMCs. Also, reduced proportions of FoxP3 expressing CD4?CD25? T cells were detected in SLE as compared to healthy control PBMCs. Furthermore, polymorphism in IL-10 and TGF-b showed significant
association with SLE in our study population. These results indicate that accumulation of superantigen-reactive T cells and cytokine polymorphism may cause disease exacerbation, relapse, or therapeutic resistance in SLE patients. Attempts to contain colonizing and/or superantigen-producing microbial agents in SLE patients in addition to careful monitoring of their therapy may be worthwhile in decreasing disease severity or preventing frequent relapses. The study suggests that superantigen interference in conjunction with cytokine polymorphism may play a role in immune dysregulation, thereby contributing to autoimmunity in SLE. Therefore, changes in T cell phenotypes and cytokine secretion might be good indicators of therapeutic efficacy in these patients.
& Shukla Das [email protected]
Keywords Autoimmunity Systemic lupus erythematosus Superantigens T cells Cytokine polymorphism
1
Department of Microbiology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India
2
Department of Biology, College of Science, University of Bahrain, Sakhir, Kingdom of Bahrain
Introduction
3
Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
4
Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha, Kingdom of Saudi Arabia
5
Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia
6
Department of Dermatology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India
7
Department of Biochemistry, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of uncertain cause with a varied clinical course and characterized by the producti
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