Characterisation of renal immune cell infiltrates in children with nephrotic syndrome.
There is increasing evidence that not only T cells but also B cells may play an important role in the pathogenesis of idiopathic nephrotic syndrome (NS). We have evaluated the infiltrating immune cells found in renal biopsies from 38 children with NS using immunohistochemistry techniques involving antibodies against T cells (CD3, CD4, CD8, FoxP3), B cells (CD20), macrophages (CD68) and follicular dendritic cells (CD21). Kidney biopsies with thin basement membrane disease were used as controls. We found higher numbers of interstitial CD3-positive T cells and macrophages in patients with focal segmental glomerulosclerosis (FSGS) than in those with minimal change glomerulopathy (MCGN) and in the controls, and significantly lower FoxP3-positive cells in patients with FSGS, MCGN and steroid-dependent NS than in the controls. Significantly higher numbers of glomerular B cells were found in FSGN patients than in MCGN patients and controls. Of note, in three patients who were later successfully treated with anti-CD20 antibody rituximab, the number of renal B cells was negligible in the preceding biopsy. In conclusion, the higher numbers of interstitial CD3-positive T cells in renal biopsies of pediatric patients with FSGS argue for a higher inflammatory activity. The significantly higher number of glomerular B cells in FSGS patients may indicate a particular pathogenetic role or epiphenomenon in this disease. However, patients with no interstitial or glomerular B cells could also benefit from rituximab treatment.
Benz
Kerstin
K
Klinik für Kinder und Jugendliche, Friedrich-Alexander-Universität Erlangen-Nürnberg, Loschgestrasse 15, 91054 Erlangen, Germany. kerstin.benz@uk-erlangen.de
Büttner
Maike
M
Dittrich
Katalin
K
Campean
Valentina
V
Dötsch
Jörg
J
Amann
Kerstin
K
D000293:Adolescent; D015703:Antigens, CD / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D020566:Dendritic Cells, Follicular / Q000378:metabolism / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D007678:Kidney Glomerulus / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D012157:Mononuclear Phagocyte System / Q000378:metabolism / Q000473:pathology*; D009402:Nephrosis, Lipoid / Q000276:immunology / Q000473:pathology*; D009404:Nephrotic Syndrome / Q000276:immunology / Q000473:pathology*; D012189:Retrospective Studies; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
Pediatr Nephrol. 2008 Aug;23(8):1269-79
18465150
Clin Nephrol. 2003 Oct;60(4):242-7
14579938
N Engl J Med. 2003 Jul 10;349(2):125-38
12853585
Pediatr Nephrol. 2008 Jan;23(1):3-7
17899207
Kidney Int. 2000 Feb;57(2):510-7
10652027
Clin Sci (Lond). 2004 Aug;107(2):125-36
15157184
Pediatr Nephrol. 2006 Nov;21(11):1698-700
16932900
Am J Nephrol. 2005 Mar-Apr;25(2):132-7
15855740
J Am Soc Nephrol. 2006 Oct;17(10):2731-41
16988067
N Engl J Med. 2008 Dec 4;359(23):2492-4
19052132
Nephrol Dial Transplant. 2006 May;21(5):1365-72
16449275
Lancet. 1974 Sep 7;2(7880):556-60
4140273
Am J Kidney Dis. 2002 May;39(5):958-65
11979339
Chest. 1990 Jun;97(6):1408-11
2347227
J Am Soc Nephrol. 2009 Jan;20(1):57-67
19020006
Kidney Int. 1991 Sep;40(3):453-60
1787645
Kidney Int. 2008 Jan;73(1):117-25
17943078
J Am Soc Nephrol. 2001 Aug;12(8):1648-1658
11461937
Pediatr Nephrol. 2004 Jul;19(7):794-7
15071769
Am J Transplant. 2008 Jan;8(1):222-7
17979998
J Nephrol. 2005 May-Jun;18(3):328-33
16013025
J Am Soc Nephrol. 2005 Sep;16(9):2615-25
15987750
Transplantation. 2008 Sep 27;86(6):772-8
18813100
Am J Pathol. 2009 May;174(5):1575-87
19349365
Eur J Pediatr. 1981 Feb;135(3):229-37
7227377
Lancet. 2002 Sep 21;360(9337):923-4
12354476
J Pediatr. 1973 Nov;83(5):767-71
4742569
Clin Chim Acta. 2000 Jul;297(1-2):123-33
10841914
Eur J Immunol. 1995 Jun;25(6):1497-501
7614976
N Engl J Med. 2007 Jun 28;356(26):2751-2
17596616
Pediatr Nephrol. 2009 Sep;24(9):1683-90
19499249