Detection of abnormal peripheral blood mononuclear cell cytokine networks in human IgA nephropathy.
Dysregulated cytokine expression has been implicated in the pathogenesis of IgA nephropathy, but the mechanisms and selectivity of this response are poorly understood. In this study we have examined the expression of a range of immunoregulatory cytokine mRNAs by peripheral blood mononuclear cells (PBMNCs) from 45 patients with IgA nephropathy stratified empirically according to urinary red cell excretion: 10 in remission, and 35 with active disease (21 mild, 14 moderate), and 17 normal, and 15 disease, controls. We used a semi-quantitative polymerase chain reaction (PCR) technique. None of the patients had experienced recent episodes of macroscopic hematuria. Simultaneous analysis of monocyte class II antigen (DR) expression was also performed by two-color immunoflow cytometry. TGF-beta 1 mRNA was detected in 68% (24 of 35) of patients with active, and 70% (7 of 10) inactive IgA nephropathy, but in only 18% (3 of 17) normal (P < 0.005), and 27% (4 of 15) disease controls. IL-6 transcripts were identified in 37% (13 of 35) of patients with active IgA nephropathy, compared with 6% (1 of 17) normal controls (P = 0.015), with no significant increase in IgA remission, or disease control groups. TNF-alpha mRNA was detected in 29% (5 of 17) of normal and 53% (8 of 15) disease controls, but in only 7% (3 of 35) of patients with IgA nephropathy (P = 0.015). There was no significant change in TGF-beta 2, gamma-IFN, IL-2, IL-4, IL-1 alpha or IL-1 beta detection between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
de Caestecker
M P
MP
Department of Nephrology, Manchester Royal Infirmary and University, United Kingdom.
Bottomley
M
M
Telfer
B A
BA
Hutchinson
I V
IV
Vose
B M
BM
Ballardie
F W
FW
D000328:Adult; D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005922:Glomerulonephritis, IGA / Q000097:blood*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D015345:Oligonucleotide Probes / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D015345:Oligonucleotide Probes; D012333:RNA, Messenger