mRNA quantification of T-bet, GATA-3, IFN-gamma, and IL-4 shows a defective Th1 immune response in the peripheral blood from rheumatoid arthritis patients: link with disease activity.
A T helper (Th)1 cytokine profile is predominant in the inflamed synovium of rheumatoid arthritis (RA). Since the situation in the blood is more controversial, we studied the Th1/Th2 balance in the peripheral blood of RA patients using mRNA markers. Total RNA was isolated directly from whole blood from 20 RA patients and 14 healthy controls. T-bet and GATA-3 transcription factors associated with Th1 and Th2 responses respectively, and IFNgamma and IL-4 mRNA levels were measured by real-time PCR. In RA but not in control samples, T-bet mRNA levels correlated positively with IFNgamma mRNA levels, and negatively with CRP levels. Accordingly, RA patients were divided into two groups according to CRP levels. In comparison to RA patients with a low CRP (CRP < 40 mg/l), patients with a high CRP (CRP>or=40 mg/l) had lower IFNgamma/beta-actin, T-bet/beta-actin mRNA levels and T-bet/GATA-3 expression ratios. In conclusion, RA blood cells showed a decreased Th1 situation as indicated by low IFNgamma and T-bet mRNA expression. This pattern was found only in patients with the most active disease.
Department of Immunology and Rheumatology and INSERM U-403, Hospital Edouard Herriot, Lyon, France.
Masanori
M
Kawashima
Pierre
P
Miossec
D000328:Adult; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000235:genetics / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000097:blood*; D020825:T-Box Domain Proteins; D018417:Th1 Cells / Q000276:immunology* / Q000473:pathology; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000098815:T-bet Transcription Factor
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D015534:Trans-Activators; D014157:Transcription Factors; D015847:Interleukin-4; D007371:Interferon-gamma; D002097:C-Reactive Protein