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1.
Clin Exp Immunol ; 167(3): 499-504, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22288593

ABSTRACT

In patients with human immunodeficiency virus (HIV) infection, neutrophil and monocyte functions, including phagocytosis, are impaired. The purpose of this study was to investigate changes of phagocytic function and respiratory burst occurring over the course of patients infected by the HIV-1 virus. Treatment-naive patients (group B), patients receiving highly active anti-retroviral treatment (HAART) (group C) and patients in which HAART has failed (group D) were studied and compared with healthy volunteers (group A). Phagocytosis and oxidative burst were evaluated using commercially available kits. Results clearly denote a significant decrease of the phagocytic function of both cell types of groups B and C compared with group A. Among group C patients, those in the upper quartile of CD4 increase had higher oxidative burst compared with patients of the other quartiles. In addition, comparisons clearly showed a lower degree of phagocytic function and of oxidative burst of both monocytes and neutrophils of group D compared with group B. Finally, it was found that monocyte and neutrophil function was correlated inversely to the change in viral load, i.e. the greater the decrease of viral load, the better the phagocytic and oxidative activity. Innate immunity defects appear to be present in HIV-positive patients, regarding phagocytic activity and oxidative burst of monocytes and neutrophils. These defects are greatly influenced by the level of treatment efficacy, with emphasis on CD4 cell counts and viral load.


Subject(s)
Antiretroviral Therapy, Highly Active , HIV Infections/drug therapy , HIV Infections/immunology , Phagocytosis , CD4 Lymphocyte Count , Case-Control Studies , HIV Infections/virology , HIV-1 , Humans , Immunity, Innate , Monocytes/immunology , Neutrophils/immunology , Respiratory Burst , Treatment Failure , Treatment Outcome , Viral Load
2.
Arthritis Rheum ; 52(2): 501-13, 2005 Feb.
Article in English | MEDLINE | ID: mdl-15693003

ABSTRACT

OBJECTIVE: Autoreactive B cells play a key role in tissue injury in systemic autoimmune disease, and therefore a treatment resulting in B cell depletion could have benefit. This open-label study was undertaken to evaluate the efficacy of the anti-CD20 monoclonal antibody rituximab in the treatment of lupus nephritis. METHODS: Lupus patients with active proliferative nephritis (4 with focal disease and 6 with diffuse disease) received rituximab (4 weekly infusions of 375 mg/m(2)) combined with oral prednisolone. Clinical, laboratory, and immunologic responses, including peripheral lymphocyte subsets measured by flow cytometry, were prospectively assessed at monthly intervals for 12 months. Complete remission of nephritis was defined as normal serum creatinine and albumin levels, inactive urine sediment, and 24-hour urinary protein <500 mg. Partial remission was defined as >50% improvement in all renal parameters that were abnormal at baseline. RESULTS: B cell depletion lasted from 1 month to 7 months and was well tolerated. Partial remission was achieved in 8 of 10 patients within a median of 2 months (range 1-4 months); in 5 of them, complete remission was subsequently established (at a median of 3 months from baseline), and it was sustained at 12 months in 4. As early as 1 month from baseline, the expression of the costimulatory molecule CD40 ligand on CD4+ T cells was decreased by 4-fold, and it was almost blocked when partial remission was clinically evident. The expression of T cell activation markers CD69 and HLA-DR was significantly decreased at time points when partial remission was observed, and was further decreased during complete remission. In contrast, in patients who did not exhibit a response or when relapse was detected in patients in whom an initial remission had been achieved, such decreases were not prominent. Serum concentrations of double-stranded DNA autoantibodies were decreased in all patients, regardless of clinical outcome. CONCLUSION: Following B cell depletion, clinical remission of lupus nephritis is associated with a decrease in T helper cell activation, suggesting an additional role for B cells, independent of autoantibody production, in promoting disease. A controlled trial to confirm these promising clinical results is warranted.


Subject(s)
Antibodies, Monoclonal/therapeutic use , B-Lymphocytes/immunology , CD40 Ligand/physiology , Lupus Nephritis/drug therapy , Adult , Antibodies, Monoclonal/administration & dosage , Antibodies, Monoclonal, Murine-Derived , Antigens, CD/analysis , Antigens, Differentiation, T-Lymphocyte/analysis , CD4-Positive T-Lymphocytes/immunology , CD40 Ligand/analysis , Down-Regulation , Female , HLA-DR Antigens/analysis , Humans , Lectins, C-Type , Leukocyte Reduction Procedures , Lupus Nephritis/immunology , Male , Prednisolone/administration & dosage , Prospective Studies , Rituximab
3.
J Interferon Cytokine Res ; 21(10): 861-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11710999

ABSTRACT

To evaluate the safety and antiviral action of interferon-alpha (IFN-alpha) in HIV-1 infection, we undertook a proof of concept study in 27 treatment-naive patients. Eligible patients comprised two groups: the IFN-alphaT group (n = 17), which received 5 MIU IFN-alpha s.c. daily for 32 consecutive days, and the IFN-alphaNT group (n = 10), which did not receive IFN-alpha prior to highly active antiretroviral therapy (HAART), which was commenced on day 28 in both groups. IFN-alphaTreatment was well tolerated in 14 of the 17 patients of the IFN-alphaT group who completed the study. The mean HIV RNA reduction in the IFN-alphaT group on day 14 was 1.1 log(10). Viral load suppression was inversely associated with baseline viral load (p = 0.031). Four weeks after initiation of HAART, IFN-alphaT and IFN-alphaNT group patients had 2.40 and 1.82 log(10) HIV RNA reduction from baseline, respectively (p < 0.001). There was no evidence of cross-resistance with existing antiretrovirals in patients with HIV-RNA rebound after initial plasma viral load decline > or = 1 log(10) during IFN-alpha monotherapy. Thus, low daily IFN-alpha exhibits potent anti-HIV-1 activity in vivo without serious adverse effects. These properties render IFN-alpha an attractive candidate for further assessment as a constituent of HAART.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1/drug effects , Interferon-alpha/therapeutic use , Virus Replication/drug effects , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/adverse effects , Antiretroviral Therapy, Highly Active , Drug Resistance, Viral , Drug Therapy, Combination , Female , HIV Infections/immunology , HIV Infections/virology , HIV-1/genetics , HIV-1/isolation & purification , Humans , Interferon-alpha/administration & dosage , Interferon-alpha/adverse effects , Kinetics , Lymphocyte Count , Male , RNA, Viral/analysis , Treatment Outcome , Viral Load
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