Superantigens and their Association with Dermatological Inflammatory Diseases: Facts and Hypotheses

Abstract

Superantigens have been suggested to play an important role in the pathogenesis of several inflammatory skin diseases as well as systemic diseases such as atopic dermatitis, psoriasis, vasculitis, T-cell lymphoma and autoimmune diseases. Infections often precede the onset and relapse of these diseases, and antibiotic treatment with or without additional glucocorticosteroids and immunoglobulins is occasionally successful. Superantigens are microbial proteins that are able to stimulate up to 20% of the naive T-cell population in a non-specific way. They are produced by gram-positive and -negative bacteria as well as by viruses, parasites and yeasts. The importance of the pathogenic role of superantigens is determined by the potency to induce inflammation by extensive cytokine release after T-cell stimulation and/or T-cell-mediated cytotoxicity and, thereby, tissue damage. Furthermore, superantigens may be able to induce autoimmune processes by stimulation of autoreactive T-cells as well as autoantibody production by stimulation of B-cells. Among the diseases associated with superantigens, atopic dermatitis, guttate and chronic plaque psoriasis, as well as Kawasaki disease, are by far the best-characterized. Nevertheless, conflicting results have been obtained and formal proof of a pathogenic role of superantigens in these diseases is still lacking. The aim of this review is to summarize the data on superantigens in terms of their distribution in microorganisms, their interactions with the adaptive immune system and their contribution to skin pathology.

Auto-presentation of Staphylococcal enterotoxin A by mouse CD4<sup>+</sup> T cells

“…Cells were centrifuged at 200 × g at 4˚C for 10 min. Red blood cells were then lysed by adding 5 mL of red cell lysis buffer (0.15 M NH 4 Cl, 10 mM KHCO 3 , 0.1 mM Na 2 EDTA). Cells were again centrifuged and resuspended in Russ-10 medium, and viable cells were counted using trypan blue and a hemocytometer.…”

“…SAg plays an important role in pathogenesis by undermining the specificity of the adaptive immune response. They are reported to be associated with etiology of several human diseases including toxic shock syndrome, Kawasaki disease, guttate psoriasis, eczema, rheumatoid arthritis and scarlet fever [4].…”

A microbiological approach to acne vulgaris.

“…Other products of propionibacteria are phosphatases, neuraminidases, deoxyribonucleases and namely substances close to prostaglandins with marked importance in the formation of inflammatory manifestations of acne 5,49,51 . Other bacteria of cutaneous microflora [namely Staphylococcus epidermidis] can also produce the above given enzymes and get involved in the acne etiology 5,16,19 . Immune mechanisms also contribute to the formation of reactive inflammation.…”

"Avaliação da resposta proliferativa das células mononucleares do sangue periférico às enterotoxinas A e B do Staphylococcus aureus e dos níveis de interleucina-18 na dermatite atópica do adulto"

“…Um superantígeno se liga como uma proteína não processável, nas regiões não polimórficas das moléculas de classe II do MHC, na superfície da célula apresentadora de antígeno (APC), que são regiões distintas da área habitual de ligação do antígeno convencional (Jappe, 2000). Os superantígenos interagem com um grande número de células T, as quais compartilham seqüências particulares nas regiões variáveis da cadeia β (Vβ) do receptor de célula T (TCR) e, por sua vez, estimulam cerca de 20% da população de células T naive (Figura 3).…”

“…Os superantígenos são moléculas bifuncionais: a porção aminoterminal tem uma alta afinidade de ligação à cadeia α de classe II do MHC (receptor de superantígeno); já a porção carboxi-terminal é responsável por uma forte ligação com o TCR (Jappe, 2000).…”