Strong polarization toward th1 immune response in ANCA-associated glomerulonephritis

K. Masutani, M. Tokumoto, H. Nakashima, K. Tsuruya, M. Kashiwagi, Y. Kudoh, K. Fukuda, H. Kanai, M. Akahoshi, T. Otsuka, H. Hirakata, M. Ida

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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-γ 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-γ 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.

Original languageEnglish
Pages (from-to)395-405
Number of pages11
JournalClinical nephrology
Volume59
Issue number6
DOIs
Publication statusPublished - Jun 1 2003

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Masutani, K., Tokumoto, M., Nakashima, H., Tsuruya, K., Kashiwagi, M., Kudoh, Y., Fukuda, K., Kanai, H., Akahoshi, M., Otsuka, T., Hirakata, H., & Ida, M. (2003). Strong polarization toward th1 immune response in ANCA-associated glomerulonephritis. Clinical nephrology, 59(6), 395-405. https://doi.org/10.5414/CNP59395