Strong polarization toward Th1 immune response in ANCA-associated glomerulonephritis
Autor: | M. Akahoshi, Kyoichi Fukuda, Teruhisa Otsuka, Mitsuo Iida, Hitoshi Nakashima, Kazuhiko Tsuruya, Minoru Kashiwagi, Masanori Tokumoto, Kohsuke Masutani, Hidetoshi Kanai, Hideki Hirakata, Y Kudoh |
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Rok vydání: | 2003 |
Předmět: |
Adult
CD4-Positive T-Lymphocytes Male medicine.medical_treatment Kidney Antibodies Antineutrophil Cytoplasmic Nephropathy Interferon-gamma Glomerulonephritis Th2 Cells Focal segmental glomerulosclerosis Immune system Membranous nephropathy medicine Humans RNA Messenger Interleukin 4 Aged biology Reverse Transcriptase Polymerase Chain Reaction business.industry General Medicine Middle Aged Th1 Cells Flow Cytometry medicine.disease Immunohistochemistry Cytokine Nephrology Case-Control Studies Immunology biology.protein Female Interleukin-4 Antibody business |
Zdroj: | Clinical Nephrology. 59:395-405 |
ISSN: | 0301-0430 |
Popis: | AIM: Human immune response can be classified into 2 different subsets of T helper cells (Th1 and Th2) based on the pattern of cytokine production. In modern immunology, Th1/Th2 paradigm helps to explain the different inflammatory effector pathways and outcomes in human diseases. The present study was designed to determine the type of immunological response that influences anti-neutrophil cytoplasmic antibody-(ANCA) associated glomerulonephritis (GN) using cytokine analysis of peripheral T cells and diseased kidney tissues. PATIENTS AND METHODS: We analyzed peripheral blood Th1/Th2 ratio in 91 patients with primary GN, including 10 cases of ANCA-associated GN. Tissues were immunostained with markers of T cells and macrophages and osteopontin (OPN). Intrarenal expression of IFN-gamma and IL-4 mRNAs was evaluated by reverse transcriptase (RT)-PCR. RESULTS: Peripheral Th1/Th2 ratio was significantly higher in ANCA-associated GN (19.4 +/- 9.4, mean +/- SD, n = 10), than those in healthy controls (7.6 +/- 4.1, n = 27), IgA nephropathy (9.6 +/- 5.6, n = 45), membranous nephropathy (7.1 +/- 4.4, n = 13), minimal-change nephrotic syndrome (8.2 +/- 4.5, n = 13) and focal segmental glomerulosclerosis (8.3 +/- 3.9, n = 10) (p < 0.01, each). In 7 of 10 cases of ANCA-associated GN, Th1/Th2 ratio decreased significantly after treatment with corticosteroid from 21.0 +/- 12.0 to 9.0 +/- 6.6 (p < 0.05). Immunohistochemical staining showed numerous infiltrating T cells, macrophages and OPN-positive cells in both glomerular tuft and cellular crescent; OPN-positive cell distribution was similar to that of macrophages. Intrarenal expression of IFN-gamma mRNA was strongly enhanced whereas a weak expression of IL-4 mRNA was observed especially in advanced cases showing tubulointerstitial injury. CONCLUSION: Both peripheral and renal immune responses are strongly polarized toward Th1 type immune response in ANCA-associated GN. Peripheral Th1/Th2 ratio may reflect the immune responses in renal injury of ANCA-associated GN. |
Databáze: | OpenAIRE |
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