Generic placeholder image

Infectious Disorders - Drug Targets


ISSN (Print): 1871-5265
ISSN (Online): 2212-3989


Role of Superantigens in Various Childhood Inflammatory Diseases

Author(s): Samileh Noorbakhsh*, Sarvenaz Ashouri and Masoumeh Moradkhani

Volume 22, Issue 7, 2022

Published on: 01 August, 2022

Article ID: e300522205404 Pages: 5

DOI: 10.2174/1871526522666220530141031


Superantigens (Sags) are a part of some viral or bacterial proteins that stimulate T cells and antigen-presenting cells leading to systemic immune repose and inflammation. SAgs might have a possible role in various inflammatory childhood diseases (e.g., Kawasaki disease, atopic dermatitis, and chronic rhinosinusitis). Worldwide studies have been conducted to determine the role of staphylococcal SAgs (TSST-1) in various inflammatory diseases. The SAgs (TSST-1) not only induce sepsis and septic shock (even in negative blood culture for S. aureus), but may also have a significant role in various childhood inflammatory diseases (e.g., KD, OMS, Polyp, dermatitis, psoriasis). In proven Sags-induced inflammatory diseases, the inhibition of the cell-destructive process by SAgs suppressants might be helpful. In toxic shock or sepsis-like presentation and even in cases with negative blood cultures, immediate use of anti staphylococcal drugs is required. Occasionally, the clinical presentation of some human viruses (e.g., coronavirus and adenovirus) mimics KD. In addition, coinfection with adenovirus, coronavirus, and para-influenza virus type 3 has also been observed with KD. It has been observed that in developed KD, bacterial sags induced an increase in acute-phase reactants and in the number of white blood cells, and neutrophil counts. Multisystem inflammatory syndrome in children (MISC) and KS were observed during the recent COVID-19 pandemic. This study summarized the relationship between viral and bacterial SAgs and childhood inflammatory diseases.

Keywords: Superantigens (Sags), MISC (multisystem inflammatory syndrome in children), COVID 19, S. aureus, adenovirus, white blood cells.

Patrick SM. Role of superantigens in human disease. J Infect Dis 1993; 167(5): 997-1002.
Stow NW, Douglas R, Tantilipikorn P, Lacroix JS. Superantigens 2003; 43: pp. (3)489-502.
Proft T, Fraser JD. Bacterial superantigens. Clin Exp Immunol 2003; 133: 299-306.
Herman A, Kappler JW, Marrack P, Pullen AM. Superantigens: Mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol 1991; 9(1): 745-72.
[] [PMID: 1832875]
Proft T, Moffatt SL, Berkahn CJ, Fraser JD. Identification and characterization of novel superantigens from Streptococcus pyogenes. J Exp Med 1999; 189(1): 89-102.
[] [PMID: 9874566]
Langley RJ, Fraser JD, Proft T. Bacterial superantigens and superantigen-like toxins.In: The comprehensive sourcebook of bacterial protein toxins. (4th ed.). Boston: Academic Press 2015; pp. 911-74.
DeDio RM, Tom LW, McGowan KL, Wetmore RF, Handler SD, Potsic WP. Microbiology of the tonsils and adenoids in a pediatric popula-tion. Arch Otolaryngol Head Neck Surg 1988; 114(7): 763-5.
[] [PMID: 3382530]
Wertheim HF, Melles DC, Vos MC, et al. The role of nasal carriage in Staphylococcus aureus infections. Lancet Infect Dis 2005; 5(12): 751-62.
[] [PMID: 16310147]
Zautner AE, Krause M, Stropahl G, et al. Intracellular persisting Staphylococcus aureus is the major pathogen in recurrent tonsillitis. PLoS One 2010; 5(3): e9452.
[] [PMID: 20209109]
Radcliff FJ, Clow F, Mahadevan M, et al. A potential role for Staphylococcal and Streptococcal superantigens in driving skewing of TCR Vβ subsets in tonsillar hyperplasia. Med Microbiol Immunol (Berl) 2017; 206(4): 337-46.
[] [PMID: 28474248]
Floret D. Clinical aspects of Streptococcal and Staphylococcal toxic diseases Arch Pediatr 2001; 8(Supple 4): 762s-768s7.
Durand G, Bes M, Meugnier H, et al. Etienne Detection of new methicillin-resistant Staphylococcus aureous clones containing containing the toxic shock syndrome toxin 1 gene responsible for hospital- and community-acquired infections in France. J Clin Microbiol 2006; 44(8): 3053.
Holtfreter S, Broker BM. Staphylococcal superantigens: Do they play a role in sepsis? Arch Immunol Ther Exp 2005; 53(1): 13-27.
Krakauer T. Staphylococcal superantigens: Pyrogenic toxins induce toxic shock. Toxins (Basel) 2019; 11(3): 178.
[] [PMID: 30909619]
Javadinia Sh, Asgarian R, Soboti B, Shokrollahi MR, Tabatabaei A. Toxic shock syndrome toxin level in wound samples of hospitalized children with burn: A case control. TUMJ 2014; 72(2): 113-20.
White MC, Thornton K, Young AE. Early diagnosis and treatment of toxic shock syndrome in paediatric burns. Burns 2005; 31(2): 193-7.
[] [PMID: 15683692]
Kristin ASL, Kern RC. Chronic rhinosinusitis and superantigens otolaryngologic clinics of North America. Otolaryngol Clin 2005; 38(6): 1215-36.
Conley DB, Tripathi A, Seiberling KA, et al. Superantigens and chronic rhinosinusitis II: Analysis of T-cell receptor V beta domains in nasal polyps. Am J Rhinol 2006; 20(4): 451-5.
[] [PMID: 16955778]
Bachert C, Zhang N, Patou J, van Zele T, Gevaert P. Role of staphylococcal superantigens in upper airway disease. Curr Opin Allergy Clin Immunol 2008; 8(Issue 1): 34-8.
Farhadi M, Tabatabaei A, Shekarabi M. Superantigens in polyp tissue of patients with chronic rhino-sinusitis.comparative study: A brief report. TUMJ 2012; 70(7): 452-6.
Noorbakhsh S, Farhadi M, Tabatabaei A. Staphylococcal superantigens; toxic shock syndrome toxin-1 and enterotoxins in pediatric otitis media effusion: A brief report. TUMJ 2013; 70(12): 793-7.
Taskapan MO, Kumar P. Role of staphylococcal superantigens in atopic dermatitis: From colonization to inflammation. Ann Allergy Asthma Immunol 2000; 84(1): 3-10.
[] [PMID: 10674558]
Muluk NB. Altın F, Donald Y. M. Leung C Cingi, Schlievert Patrick M. Role of superantigens in allergic inflammation: Their relationship to allergic rhinitis, chronic rhinosinusitis, asthma, and atopic dermatitis. Am J Rhinol Allergy 2018; 32(6): 502-17.
Nowrouzian FL, Ljung A, Nilsson S, Hesselmar B, Adlerberth I, Wold AE. Neonatal gut colonization by Staphylococcus aureus strains with certain adhesins and superantigens is negatively associated with subsequent development of atopic eczema. Br J Dermatol 2019; 180(6): 1481-8.
[] [PMID: 30474111]
Atefi N, Tabaie M, Tabatabaie A, Rezaee MR, Rohaninasab M. The role of Staphylococcus superantigens in chronic plaque type psoriasis Iranian. J Dermatol 2012; 15(1): 1-3.
Atefi N, Noorbakhsh S, Ghavidel Darestani S, Tabatabaei A, Rezaee M. The rise of staphylococcal super antigens in psoriatic patients: A case-control study. Jundishapur J Microbiol 2014; 7(5): e9912.
[] [PMID: 25147719]
Schutyser E, Struyf S, Wuyts A, et al. Selective induction of CCL18/PARC by staphylococcal enterotoxins in mononuclear cells and en-hanced levels in septic and rheumatoid arthritis. Eur J Immunol 2001; 31(12): 3755-62.
[<3755:AID-IMMU3755>3.0.CO;2-O] [PMID: 11745396]
Shokrollahi MR, Tabatabaei Aliakbari A. Searching the staphylococcal superantigens: Enterotoxins A, B, C, and TSST1 in synovial fluid of cases with negative culture inflammatory arthritis jundishapur. J Microbiol 2014; 7(7): e11647.
Chapaval L, Moon DH. Gomes, Tsai SM. An alternative method for s aureus DNA isolation. Arq Bras Med Vet Zootec 2008; 60(2): 299-306.
Harris LG, Foster SJ, Richards RG. An introduction to Staphylococcus aureus, and techniques for identifying and quantifying S. aureus adhesins in relation to adhesion to biomaterials: Review. Eur Cell Mater 2002; 4: 39-60.
[] [PMID: 14562246]
EI-Ghodban A. Ghenghesh KHS, Ma Rialigeti K, et al PCR Detection of toxic shok syndrom toxin of Staphylococcus aureus. Tripoli J Microbiol 2006; pp. 179-82.
Merriman JA, Schlievert PM. Identification, purification, and characterization of staphylococcal superantigens. Methods Mol Biol 2016; 1396: 19-33.
Kaempfer R. Peptide antagonists of superantigen toxins. Mol Divers 2004; 8(2): 113-20.
[] [PMID: 15209162]
Arad G, Levy R, Hillman D, Kaempfer R. Superantigen antagonist protects against lethal shock and defines a new domain for T-cell activa-tion. Nat Med 2000; 6(4): 414-21.
[] [PMID: 10742148]
Kaempfer R, Arad G, Levy R, Hillman D. Defense against biologic warfare with superantigen toxins. Isr Med Assoc J 2002; 4(7): 520-3.
[PMID: 12120463]
Krakauer T. FDA-approved immunosuppressants targeting Staphylococcal superantigens: Mechanisms and insights. ImmunoTargets Ther 2017; 6: 17-29.
[] [PMID: 28497030]
Dimitriades VR, Brown AG, Gedalia A. Kawasaki disease: Pathophysiology, clinical manifestations, and management. Curr Rheumatol Rep 2014; 16(6): 423.
[] [PMID: 24744086]
McCrindle BW, Rowley AH, Newburger JW, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A scientific state-ment for health professionals from the American heart association. Circulation 2017; 135(17): e927-99.
[] [PMID: 28356445]
Leung DY, Meissner HC, Fulton DR, Murray DL, Kotzin BL, Schlievert PM. Toxic shock syndrome toxin-secreting Staphylococcus aureus in Kawasaki syndrome. Lancet 1993; 342(8884): 1385-8.
[] [PMID: 7901681]
Rowley AH. Is Kawasaki disease an infectious disorder? Int J Rheum Dis 2018; 21(1): 20-5.
[] [PMID: 29105346]
Giray T, Biçer S, Küçük Ö, et al. Four cases with Kawasaki disease and viral infection: Aetiology or association. Infez Med 2016; 24(4): 340-4.
[PMID: 28011972]
Bittmann S, Weissenstein A, Luchter E, Moschüring-Alieva E, Villalon G. Multisystem inflammatory syndrome in children (MIS-C): The role of viral superantigens in COVID-19 disease. J Allergy Infect Dis 2020; 1(1): 18-20.
Kaushik S, Aydin SI, Derespina KR, Bansal PB, Kowalsky S, Trachtman R. Multisystem inflammatory syndrome in children (MISC) asso-ciated with SARS-CoV-2 infection: A multi-institutional study from New York City. J Pediatr 2020; [Epub ahead of print].
Raba AA, Abobaker A. COVID-19 and Kawasaki disease: An etiology or coincidental infection? Pediatr Infect Dis J 2020; 39(8): e213.
[] [PMID: 32467454]
Bittmann S. Weissenstein Anne, Villalon Gloria, et al. Elisabeth Luchter: Association of COVID-19 coronavirus and Kawasaki syndrome-like features in 1-5 years old children. Neurosci Chron 2020; 1(1): 4-5.
Harwood R, Allin B, Jones CE, et al. A national consensus management pathway for paediatric inflammatory multisystem syndrome tempo-rally associated with COVID-19 (PIMS-TS): Results of a national Delphi process. Lancet Child Adolesc Health 2021; 5: 133-41.
Leung Donald YM. Kawasaki syndrome: Role of superantigens revisited. FEBS J 2021; 288(6): 1771-7.
Porritt RA, Binek A, Paschold L, et al. The autoimmune signature of hyperinflammatory multisystem inflammatory syndrome in children. J Clin Invest 2021; 131(20): e151520.
[] [PMID: 34437303]
Porritt RA, Paschold L, Rivas MN, et al. HLA class I-associated expansion of TRBV11-2 T cells in multisystem inflammatory syndrome in children. J Clin Invest 2021; 131(10): e146614.
Kouo T, Chaisawangwong W. SARS-CoV-2 as a superantigen in multisystem inflammatory syndrome in children. J Clin Invest 2021; 131(10): e149327.
[] [PMID: 33844652]
Hoste L, Roels L, Naesens L, et al. MIS-C Clinicians. TIM3+TRBV11-2 T cells and IFNγ signature in patrolling monocytes and CD16+ NK cells delineate MIS-C. J Exp Med 2022; 219(2): e20211381.
[] [PMID: 34914824]

© 2023 Bentham Science Publishers | Privacy Policy