Effects of smoking on disease activity and radiographic progression in early rheumatoid arthritis.

OBJECTIVE: To analyze the effects of cigarette smoking on disease activity and radiographic damage in patients with early rheumatoid arthritis (RA). METHODS: Study subjects were 156 patients with early RA (< 2 yrs). Disease activity, therapeutic response, and radiographic progression were compared in smokers and nonsmokers at 24 months. RESULTS: At baseline, ever-smokers had earlier disease onset and a closer association with the shared epitope (SE), but not more seropositive disease. No significant differences were observed in disease activity and European League Against Rheumatism therapeutic responses between smokers and nonsmokers. Multivariate analysis showed that baseline Larsen score, the HLA-DRB*04 genotype, being female, and current smoking were associated with radiographic progression. CONCLUSION: In patients with early RA, smoking was associated with earlier disease onset and the SE. Smoking was an independent factor of radiographic progression.

[Immunologic study of the donor-receptor couple]. / Estudio inmunológico de la pareja donante-receptor.

The objective of the study is to evaluate the risk of graft failure. The presence of donor specific alloantibodies and the HLA incompatibilities between donor and receptor must be identified. There are several methods to identify alloandibodies that has different sensitivity and different Prognostic Value. Some define a high risk of hyperacute rejection, others an increase in the risk to loss the graft in defined subgroups. First steps of the pretransplant study identify: a) HLA typing of the receptor and available donors; b) alloantibodies by Complement Dependent Cytotoxicity against Panel (PRA-CDC) and screening of alloantibodies against HLA by Solid Phase; c) in sensitized receptors it can be useful to identify acceptable incompatibilities using Single Antigen Solid Phase technique and to evaluate the «Virtual Crossmatch». Pretransplant study (10 days): a) crossmatch by Citotoxicity (CM-CDC) between receptor and donor; b) crossmatch by Flow-Cytometry (FCCM) between receptor and donor specially indicated in the retransplant. Useful also to discard IgM auto-antibodies. Receptors desensitization: the necessity and success probability of desensitization should be evaluated before treatment. Post-Transplant Monitoring: identify alloantibodies for: a) the differential diagnostic of corticorresistant rejection episodes with humoral component, and b) as a marker of long term reduced graft survival probability in the long term. Final remarks: Evaluation should consider the allosensibilization history of the receptor. The cytotoxicity crossmatch indicates a high risk of hyperacute rejection and is considered a contraindication. The Flow Cytometry crossmatch indicates an increase in the probability to loss the graft in the first year that is low for first transplants (>10%) but higher for retransplantation (>30%). The virtual crossmatch by solid phase indicates an increase in the probability to have an antibody mediated rejection (from 5% to 55%) but did not contraindicate always the transplant.

Long-term immune response after liver transplantation in patients with spontaneous or post-treatment HCV-RNA clearance.

Recurrent HCV infection after liver transplantation is universal and sustained clearance of HCV-RNA rarely occurs. The aim of this study was to characterize cell-mediated immunity and cytokine production in HCV-infected patients after liver transplant. The study included 6 pretransplantation patients (PT) and 15 liver transplanted patients, including 5 with spontaneous HCV-RNA clearance (SC group), 5 with sustained virological response after antiviral treatment (SVR group), and 5 no response (NR group). The control group included 5 HCV-RNA negative, anti-HCV negative healthy individuals. This study examines proliferative T-cell response and cytokine production (gamma-interferon and IL-10) after HCV specific and phytohemagglutinin (PHA) stimulation in cultured peripheral blood mononuclear cells (PBMCs) from each group. Multispecific proliferative responses to HCV antigens (mean Stimulation Index; SI) were higher in the SVR group (mean SI 7.4 +/- 2) and SC group, as compared with the NR group (P <.05, vs SVR) and PT group (P <.05, vs SVR and SC). After PHA stimulation, gamma-interferon levels were similar to controls (4330 +/- 640 pg/ml) in the SC (4474 +/- 300 pg/mL) and SVR groups (3647 +/- 300 pg/mL), but were significantly lower than controls in the PT (401 +/- 331 pg/mL; P <.02) and NR groups (546 +/- 360 pg/mL; P <.01). IL-10 production after PHA stimulation was similar in SC, SVR, and controls (647 +/- 279 pg/mL, 674 +/- 310 pg/mL and 841 +/- 294 pg/mL, respectively), but was lower in PT patients (232 +/- 94 pg/mL). The NR group showed high basal IL-10 production with little increase after stimulation. In conclusion, liver post-transplantation patients with spontaneous clearance of HCV-RNA and those with sustained viral response after therapy showed an immune response despite immunosuppression that might have contributed to their favorable outcome.