title: Imbalance towards Th1 pathway predominance in purpura nephritis with proteinuria.
abstract: Although recent reports suggest a possible role for an imbalance in Th1 and Th2 proinflammatory cytokines in the development and progression of glomerulonephritis, there is little information on Th1 or Th2 predominance in Henoch-Schönlein purpura nephritis (HSPN). Since T-bet and GATA-3 are transcriptional factors that regulate the differentiation of helper T lymphocytes into Th1 and Th2, we examined the relative mRNA expression of T-bet and GATA-3 in the urinary sediment of children with proteinuric HSPN by real-time quantitative PCR. Eight consecutive patients with proteinuric HSPN (4 with grade IIIa and 4 with grade IIIb according to the International Study of Kidney Disease in Children criteria) and 20 healthy subjects were enrolled in this study. The relative expression level of T-bet was significantly higher in the urinary sediment of patients with HSPN at presentation than in that of the healthy controls (p = 0.021), while the relative expression of GATA-3 was significantly lower in the urinary sediment of patients than in that of controls (p = 0.002). Urinary mRNA expression of T-bet correlated with the urinary protein/creatinine ratio (r = 0.608, p = 0.013), and correlated inversely with serum level of total protein (r = -0.574, p = 0.020). Moreover, a significantly increased intensity of T-bet immunostaining was observed in the glomeruli in the biopsy specimen of all study patients. All patients received immunosuppressive therapy. Repeat measurements of urinary mRNA expression of T-bet and GATA-3 after treatment revealed that the expression of T-bet in patients had significantly decreased relative to the baseline (p = 0.003), while the expression of GATA-3 remained static. In a patient subjected to a post-treatment renal biopsy, the increased intensity of immunostaining of T-bet had clearly diminished following immunosuppressive treatment, in accordance with a significant decrease in urinary mRNA expression of T-bet. These observations suggest that patients with proteinuric HSPN demonstrate increased T-bet and depressed GATA-3 expression in the urinary sediment, indicating a possible shift in Th1/Th2 balance towards Th1 predominance.
authors.affiliation: Department of Pediatrics, Hirosaki University Hospital, Hirosaki, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tsuruga
authors.forename: Shojiro
authors.initials: S
authors.lastname: Watanabe
authors.forename: Eishin
authors.initials: E
authors.lastname: Oki
authors.forename: Tomomi
authors.initials: T
authors.lastname: Aizawa-Yashiro
authors.forename: Hidemi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D050990:GATA3 Transcription Factor / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D006801:Humans; D011695:IgA Vasculitis / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D008297:Male; D009393:Nephritis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D011507:Proteinuria / Q000209:etiology / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020825:T-Box Domain Proteins / Q000032:analysis* / Q000096:biosynthesis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor