Strong polarization toward Th1 immune response in ANCA-associated glomerulonephritis.

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-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.

• Authors: K Masutani, M Tokumoto, H Nakashima, K Tsuruya, M Kashiwagi, Y Kudoh, K Fukuda, H Kanai, M Akahoshi, T Otsuka, H Hirakata, M Iida
• Journal: Clinical nephrology (Clin Nephrol) Vol. 59 Issue 6 Pg. 395-405 (Jun 2003) ISSN: 0301-0430 [Print] Germany
• PMID: 12834170 (Publication Type: Journal Article)

Chemical References

• Antibodies, Antineutrophil Cytoplasmic
• RNA, Messenger
• Interleukin-4
• Interferon-gamma

Topics

• Adult
• Aged
• Antibodies, Antineutrophil Cytoplasmic (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Case-Control Studies
• Female
• Flow Cytometry
• Glomerulonephritis (immunology)
• Humans
• Immunohistochemistry
• Interferon-gamma (analysis)
• Interleukin-4 (analysis)
• Kidney (immunology)
• Male
• Middle Aged
• RNA, Messenger (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Th1 Cells (immunology)
• Th2 Cells (immunology)