Strong Polarization Toward Th1 Immune Response In Anca-Associated Glomerulonephritis
CLINICAL NEPHROLOGY(2003)
Abstract
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- 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&PLUSMN;12.0 to 9.0&PLUSMN;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- 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.
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Key words
Th1/Th2 balance, intracellular cytokine detection method, anti-neutrophil cytoplasmic antibody (ANCA), interferon (IFN)-, interleukin-(IL) 4
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