ABSTRACT
BACKGROUND: Immune response failure against hepatitis C virus (HCV) has been associated with an increased regulatory T cell (Treg) activity. After liver transplantation (LT), 80% of patients experience an accelerated progression of hepatitis C recurrence. The aim of this work was to assess the involvement of Tregs, T helper (Th) 1, 2 and 17 cells in recurrent hepatitis C. METHODS: Peripheral blood cells obtained before and one month after LT from 22 recipients were analysed. Forty-four key molecules related to Treg, Th1, 2 and 17 responses, were evaluated using qRT-PCR. Liver recipients were classified in two groups according to graft fibrosis evaluated by the METAVIR score on the biopsy performed one year after LT (mild: F ≤ 1, n = 13; severe: F > 1, n = 9). Patients developing a severe recurrence were compared with patients with a mild recurrence. RESULTS: mRNA levels of Treg markers obtained one month after LT were significantly increased in patients with a severe disease course when compared to patients with a mild recurrence. Markers of the Th1 response were elevated in the same group. No differences in the markers determined before LT were observed. CONCLUSION: These findings suggest that Treg, induced by a multifactorial process, which could include a strong Th1 response itself, may play a role in suppressing the early antiviral response, leading to a severe recurrence of hepatitis C.
Subject(s)
Hepatitis C, Chronic/diagnosis , Liver Transplantation , T-Lymphocytes, Helper-Inducer/metabolism , T-Lymphocytes, Regulatory/metabolism , Aged , Biomarkers/metabolism , CD28 Antigens/genetics , CD28 Antigens/metabolism , CD40 Ligand/genetics , CD40 Ligand/metabolism , CTLA-4 Antigen/genetics , CTLA-4 Antigen/metabolism , Disease Progression , Female , Humans , Interferon-gamma/genetics , Interferon-gamma/metabolism , Interleukin-10 Receptor alpha Subunit/genetics , Interleukin-10 Receptor alpha Subunit/metabolism , Interleukin-10 Receptor beta Subunit/genetics , Interleukin-10 Receptor beta Subunit/metabolism , Interleukin-2/genetics , Interleukin-2/metabolism , Interleukin-2 Receptor alpha Subunit/genetics , Interleukin-2 Receptor alpha Subunit/metabolism , Interleukin-23/genetics , Interleukin-23/metabolism , Male , Middle Aged , RNA, Messenger/metabolism , Real-Time Polymerase Chain Reaction , Recurrence , Reverse Transcriptase Polymerase Chain Reaction , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolism , Transforming Growth Factor beta/genetics , Transforming Growth Factor beta/metabolism , Tumor Necrosis Factor Receptor Superfamily, Member 7/genetics , Tumor Necrosis Factor Receptor Superfamily, Member 7/metabolismABSTRACT
OBJECTIVE: To study the clinical risk factors for preterm premature rupture of membranes (PROM). METHOD: We conducted a case-control study of 138 patients with PROM between 24 and 35 weeks' gestation and 267 control subjects. RESULTS: In stepwise multiple logistic regression models, the population of cases was more likely to be of low social class. Other risk factors for PROM were smoking in pregnancy, 1st or 2nd-3rd trimester hemorrhages, cervical incompetence and a documented cervico-vaginal infection during index pregnancy. First trimester hemorrhage and a documented cervico-vaginal infection during index pregnancy were associated with preterm PROM both in nulliparous and in multiparous women. CONCLUSION: Few potentially remediable risk factors are associated with the occurrence of preterm PROM.