Analysis of T-cell receptor usage in myeloperoxidase--antineutrophil cytoplasmic antibody-associated renal vasculitis.
BACKGROUND
Bacterial superantigens produced by Staphylococcus aureus may be associated with the onset of proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA)-associated vasculitis, including Wegener's granulomatosis. We investigated T-cell subsets to assess the superantigens present in patients with myeloperoxidase-antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis.


METHODS
Peripheral-blood mononuclear cells (PBMC) obtained from 40 normal controls and ten patients with MPO-ANCA-associated vasculitis were stained with fluorescence-labeled monoclonal antibodies against T-cell markers, including 17 variable regions of T-cell receptor beta-chains (TCR-Vbeta) and were then analyzed using flow cytometry.


RESULTS
Among PBMCs, the percentage of CD3(+) cells from patients with MPO-ANCA-associated vasculitis was significantly lower than that from normal controls, but there were no differences between the two groups in the percentage of CD19(+) cells or CD16(+) cells. Although there were no differences regarding the overall percentage of CD4(+) cells between the two groups, the percentage of CD4(+)CD45RO(+) cells in patients with MPO-ANCA-associated vasculitis was significantly higher than that in normal controls, and percentages of CD4(+)CD45RO(+)HLA-DR(+) and CD4(+)CD45RO(+)CD62L(low) cells in patients with MPO-ANCA-associated vasculitis were also significantly increased. There was no significant difference between the two groups in terms of the usage of the 17 different TCR-Vbeta regions.


CONCLUSIONS
There was no difference in bacterial superantigens between controls and MPO-ANCA-associated vasculitis patients because of the absence of specific usage of TCR-Vbeta regions. Given the elevated levels of memory T cells, conventional antigens rather than superantigens may be associated with the pathogenesis of MPO-ANCA-associated vasculitis.
Hirayama
Kouichi
K
Department of Nephrology, Tokyo Medical University Ibaraki Medical Center, 3-20-1 Chuo, Ami, Ibaraki, 300-0395, Japan, k-hira@tokyo-med.ac.jp.
Ishizu
Takashi
T
Shimohata
Homare
H
Miyamoto
Yasunori
Y
Kakita
Tomoko
T
Nagai
Miho
M
Ogawa
Yujiro
Y
Fujita
Shogo
S
Hirayama
Aki
A
Yamagata
Kunihiro
K
Kobayashi
Masaki
M
Koyama
Akio
A
D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053146:Myeloblastin / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014657:Vasculitis / Q000276:immunology*
D019268:Antibodies, Antineutrophil Cytoplasmic; D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D009195:Peroxidase; D053146:Myeloblastin