title: Inverse correlation between CD4+ regulatory T-cell population and autoantibody levels in paediatric patients with systemic lupus erythematosus.
abstract: CD4(+) CD25(+) regulatory T cells (Tregs) are critical in maintaining self-tolerance and preventing organ-specific autoimmunity. Their role in paediatric systemic lupus erythematosus (SLE), an autoimmune disease characterized by inappropriate regulation of hyperactivated B and T cells, has not been clearly defined. Using flow cytometry to determine cell populations and real-time polymerase chain reaction to assay mRNA expression for FOXP3, CTLA-4, and GITR, we characterized CD4(+) CD25(+) T cells in paediatric SLE patients and healthy subjects. The frequency of CD4(+) CD25(+) Tregs was significantly decreased in patients with active SLE compared with patients with inactive SLE and with controls (7.27% +/- 2.50%, 9.59% +/- 2.80% and 9.78% +/- 2.11%, respectively; P = 0.027 and P < 0.001, respectively), and was inversely correlated with disease activity, as assessed with the Systemic Lupus Erythematosus Disease Activity Index 2000 scores (r = -0.59, P = 0.001) and serum anti-double-stranded DNA levels (r = -0.65, P < 0.001). Our preliminary investigations found elevated surface expression of GITR in CD4(+) CD25(+) T cells, elevated mRNA expression of CTLA-4 in CD4(+) T cells and higher amounts of mRNA expression for FOXP3 in CD4(+) cells in patients with active SLE compared with patients with inactive disease and controls. We demonstrated reduced CD4(+) CD25(+) Treg levels were inversely correlated with disease activity, indicating a defective Treg population in paediatric SLE patients. The differences in the expression of FOXP3, CTLA-4 and GITR imply the possible role of CD4(+) Tregs in the pathogenesis of SLE.
authors.affiliation: Department of Paediatrics, National Taiwan University Hospital, Taipei.
authors.forename: Jyh-Hong
authors.initials: JH
authors.lastname: Lee
authors.forename: Li-Chieh
authors.initials: LC
authors.lastname: Wang
authors.forename: Yu-Tsan
authors.initials: YT
authors.lastname: Lin
authors.forename: Yao-Hsu
authors.initials: YH
authors.lastname: Yang
authors.forename: Dong-Tsamn
authors.initials: DT
authors.lastname: Lin
authors.forename: Bor-Luen
authors.initials: BL
authors.lastname: Chiang
mesh_terms: D000293:Adolescent; D000974:Antibodies, Antinuclear / Q000097:blood*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000096:biosynthesis / Q000235:genetics; D060908:CTLA-4 Antigen; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D053450:Glucocorticoid-Induced TNFR-Related Protein; D006801:Humans; D016130:Immunophenotyping; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000032:analysis; D017475:Receptors, Nerve Growth Factor / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000235:genetics; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: D000974:Antibodies, Antinuclear; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053450:Glucocorticoid-Induced TNFR-Related Protein; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C491405:TNFRSF18 protein, human; D004247:DNA