title: Superantigen influence in conjunction with cytokine polymorphism potentiates autoimmunity in systemic lupus erythematosus patients.
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-β 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.
authors.affiliation: Department of Microbiology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India.|Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.
authors.forename: Sajad Ahmad
authors.initials: SA
authors.lastname: Dar
authors.affiliation: Department of Biology, College of Science, University of Bahrain, Sakhir, Kingdom of Bahrain.
authors.forename: Essam Mohammed Ahmed
authors.initials: EM
authors.lastname: Janahi
authors.affiliation: Centre for Drug Research, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.|Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.
authors.forename: Shafiul
authors.initials: S
authors.lastname: Haque
authors.affiliation: Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Albaha University, Albaha, Kingdom of Saudi Arabia.
authors.forename: Naseem
authors.initials: N
authors.lastname: Akhter
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.
authors.forename: Arshad
authors.initials: A
authors.lastname: Jawed
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Kingdom of Saudi Arabia.
authors.forename: Mohd
authors.initials: M
authors.lastname: Wahid
authors.affiliation: Department of Microbiology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India.
authors.forename: Vishnampettai Ganapathysubramanian
authors.initials: VG
authors.lastname: Ramachandran
authors.affiliation: Department of Dermatology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India.
authors.forename: Sambit Nath
authors.initials: SN
authors.lastname: Bhattacharya
authors.affiliation: Department of Biochemistry, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India.
authors.forename: Basu Dev
authors.initials: BD
authors.lastname: Banerjee
authors.affiliation: Department of Microbiology, University College of Medical Sciences (University of Delhi) and Guru Teg Bahadur Hospital, Delhi, India. shukladas_123@yahoo.com.
authors.forename: Shukla
authors.initials: S
authors.lastname: Das
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D001426:Bacterial Proteins / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018450:Disease Progression; D005098:Exotoxins / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008180:Lupus Erythematosus, Systemic / Q000188:drug therapy / Q000276:immunology*; D008213:Lymphocyte Activation; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D011110:Polymorphism, Genetic; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D005098:Exotoxins; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; C117980:SpeA protein, Streptococcus pyogenes; D016212:Transforming Growth Factor beta; C091239:staphylococcal pyrogenic exotoxin type B; D016753:Interleukin-10
keywords: Autoimmunity; Cytokine polymorphism; Superantigens; Systemic lupus erythematosus; T cells