TY - JOUR
T1 - Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch–Schönlein purpura nephritis
AU - Imai, Takashi
AU - Nishiyama, Kei
AU - Ueki, Kenji
AU - Tanaka, Tamami
AU - Kaku, Yoshitsugu
AU - Hara, Toshiro
AU - Ohga, Shouichi
N1 - Funding Information:
We thank all the patients and medical staff. We thank Dr Satoshi Hisano for his helpful comments; Ryoko Unose, Ayumi Tahara and Mikio Munakata at Kyushu University for their excellent technical assistance; Kenji Murata, MD, PhD, and Yasushi Tsutsumi, MD, for generous support; and Dr Kaori Yasuda at Cell Innovator Inc. for technical assistance. This work was supported by JSPS KAKENHI, Grant Numbers JP19K16644 and JP20K17286.
Publisher Copyright:
© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
PY - 2020
Y1 - 2020
N2 - Objectives: Immunoglobulin A vasculitis/Henoch–Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose-deficient IgA1 was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear. Methods: We compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA. Results: GNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin- and/or granzyme B-positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up-regulated surface expressions of human leucocyte antigen DR (HLA-DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8+ cells and/or CD56+ cells and up-regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level. Conclusion: Activated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN.
AB - Objectives: Immunoglobulin A vasculitis/Henoch–Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose-deficient IgA1 was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear. Methods: We compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA. Results: GNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin- and/or granzyme B-positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up-regulated surface expressions of human leucocyte antigen DR (HLA-DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8+ cells and/or CD56+ cells and up-regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level. Conclusion: Activated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN.
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U2 - 10.1002/cti2.1212
DO - 10.1002/cti2.1212
M3 - Article
AN - SCOPUS:85096591931
SN - 2050-0068
VL - 9
JO - Clinical and Translational Immunology
JF - Clinical and Translational Immunology
IS - 11
M1 - e1212
ER -
