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Nephrol Dial Transplant (2000) 15: 1170-1174
© 2000 European Renal Association-European Dialysis and Transplant Association

Cytokines and T-cell responses in superantigen-related glomerulonephritis following methicillin-resistant Staphylococcus aureus infection

Keigyou Yoh1, Masaki Kobayashi2, Naoto Yamaguchi1, Kouichi Hirayama1, Takashi Ishizu1, Shuichi Kikuchi1, Satoshi Iwabuchi1, Kaori Muro1, Sohji Nagase1, Kazumasa Aoyagi1, Makoto Kondoh1, Katsumi Takemura3, Kunihiro Yamagata4 and Akio Koyama1,

1 Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Ibaraki, 2 Department of Nephrology, Tokyo Medical University Kasumigaura Hospital, Ibaraki, 3 Department of Nephrology, Kamitsuga General Hospital, Tochigi and 4 Department of Nephrology, Hitachi General Hospital, Ibaraki, Japan

Background. We have previously reported that 10 patients who developed glomerulonephritis (GN) in association with methicillin-resistant Staphylococcus aureus (MRSA) infection showed a marked increase in DR+CD4+ and DR+CD8+ subsets of T cells and in T cells expressing several T-cell receptor (TCR) Vß+cells, perhaps representing Vß-specific T-cell activation by MRSA-derived superantigens (Kidney Int 1995; 47: 207–216). In this study we examine cytokine levels, T-lymphocyte subsets, natural killer NK cells, memory T cells, and the expression of IL-2 receptors in order to better understand the role of bacterial superantigens and cytokines in the pathogenesis of MRSA-associated GN.

Methods. Twenty-two patients with MRSA infection who later developed GN caused by staphylococcal enterotoxin were evaluated immunologically in comparison with patients whose MRSA infection was not followed by GN (non-GN group) and normal individuals.

Results. Among peripheral lymphocytes, the frequency of T cells expressing several TCR Vßs, especially Vß5-family TCR, was higher in the GN group than in both the non-GN group and the normal healthy control group. GN patients also showed increased serum levels of several cytokines, including tumour necrosis factor-{alpha} (TNF-{alpha}), interleukin-1ß (IL-1ß), IL-2, IL-6, IL-8, and IL-10, which have been implicated in the onset of nephritis. Memory cells, and IL-2 receptors also were elevated in the GN group.

Conclusion. These results suggest that T cells activated by MRSA-derived staphylococcal enterotoxins and subsequent production of cytokines may play an important role in the pathogenesis of MRSA-associated GN.

Keywords: enterotoxin; glomerulonephritis; MRSA; superantigen

Correspondence and offprint requests to: Akio Koyama, MD, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki 305–8575, Japan.


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