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 language | English |
|---|---|
| Pages (from-to) | 395-405 |
| Number of pages | 11 |
| Journal | Clinical Nephrology |
| Volume | 59 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jun 1 2003 |
Fingerprint
All Science Journal Classification (ASJC) codes
- Nephrology
Cite this
Strong polarization toward th1 immune response in ANCA-associated glomerulonephritis. / Masutani, K.; Tokumoto, M.; Nakashima, H.; Tsuruya, K.; Kashiwagi, M.; Kudoh, Y.; Fukuda, K.; Kanai, H.; Akahoshi, Mitsuteru; Otsuka, T.; Hirakata, H.; Ida, M.
In: Clinical Nephrology, Vol. 59, No. 6, 01.06.2003, p. 395-405.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Strong polarization toward th1 immune response in ANCA-associated glomerulonephritis
AU - Masutani, K.
AU - Tokumoto, M.
AU - Nakashima, H.
AU - Tsuruya, K.
AU - Kashiwagi, M.
AU - Kudoh, Y.
AU - Fukuda, K.
AU - Kanai, H.
AU - Akahoshi, Mitsuteru
AU - Otsuka, T.
AU - Hirakata, H.
AU - Ida, M.
PY - 2003/6/1
Y1 - 2003/6/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038039259&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0038039259&partnerID=8YFLogxK
U2 - 10.5414/CNP59395
DO - 10.5414/CNP59395
M3 - Article
VL - 59
SP - 395
EP - 405
JO - Clinical Nephrology
JF - Clinical Nephrology
SN - 0301-0430
IS - 6
ER -