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Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 3 2010
Sean G. O'Neill
Objective Inflammatory disease activity in patients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti,apolipoprotein A-I (anti,Apo A-I), anti,high-density lipoprotein (anti-HDL), and anti,C-reactive protein (anti-CRP) autoantibodies. We undertook this study to examine whether levels of these antibodies rise in association with increased SLE disease activity. Methods IgG anti,Apo A-I, anti-HDL, and anti-CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus nephritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. Results Serum levels of IgG anti,Apo A-I, anti-HDL, and anti-CRP were higher in patients with SLE than in controls. Anti,Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with persistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti,Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti,Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti,double-stranded DNA. Conclusion Persistent disease activity is associated with a significant increase in IgG anti,Apo A-I and anti-HDL in patients with SLE. [source]

Prospective analysis of treatment outcome and prognostic factors in patients with T-cell lymphomas treated by CEOP-B: single institutional study

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006
Hwa Jung Sung
Summary The important prognostic factors were evaluated for T-cell non-Hodgkin lymphoma (NHL) patients in a prospective study using the CEOP-B protocol [a modified cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen that uses epirubicin instead of doxorubicin with the addition of bleomycin]. Fifty-two patients were enrolled in the study. The overall response rate was 63·5%. The median progression-free survival (PFS) and median overall survival (OS) was 18·0 and 39·5 months respectively. The most common toxicity was neutropenia. The factors related to poor outcome were a high International Prognostic Index (IPI) and a high ,B' score (bone marrow involvement, B symptoms, bulky disease). We developed a new prognostic model, namely the Prognostic Group for T cell NHL (PGT) that included four groups: PGT1 (low IPI/low B score), PGT2 (low IPI/high B score), PGT3 (high IPI/Low B score) and PGT4 (high IPI/Low B score). OS and PFS (not reached, 48 months) in the PGT1 group were significantly longer than those (11·5 and 4·8 months) in PGT2. The same result was observed in the PGT3 and PGT4 groups. The CEOP-B regimen was moderately active and tolerable for T-cell NHL patients, and the PGT system might be useful for the prediction of long-term survival of T-cell NHL patients. [source]

Antibodies to apolipoprotein A-I, high-density lipoprotein, and C-reactive protein are associated with disease activity in patients with systemic lupus erythematosus

ARTHRITIS & RHEUMATISM, Issue 3 2010
Sean G. O'Neill
Objective Inflammatory disease activity in patients with systemic lupus erythematosus (SLE) may affect the development of atherosclerosis, contributing to their increased risk of cardiovascular disease (CVD). This process may be mediated by anti,apolipoprotein A-I (anti,Apo A-I), anti,high-density lipoprotein (anti-HDL), and anti,C-reactive protein (anti-CRP) autoantibodies. We undertook this study to examine whether levels of these antibodies rise in association with increased SLE disease activity. Methods IgG anti,Apo A-I, anti-HDL, and anti-CRP levels were measured in serum from the following groups: 39 patients with persistently high disease activity (British Isles Lupus Assessment Group [BILAG] A or B score) over the previous 2 years, 42 patients with persistently low disease activity (no BILAG A or B scores) over the previous 2 years, 34 healthy controls, 25 individual patients from whom paired samples (at time of disease flare and quiescence) were obtained and compared, 16 patients with newly diagnosed lupus nephritis from whom multiple samples were obtained and who were followed up prospectively for up to 2 years, and 24 patients with SLE who had experienced CVD events. Results Serum levels of IgG anti,Apo A-I, anti-HDL, and anti-CRP were higher in patients with SLE than in controls. Anti,Apo A-I and anti-HDL levels, but not anti-CRP levels, were higher in patients with persistently high disease activity than in those with low disease activity. Mean levels of the 3 autoantibodies in patients who had experienced CVD events lay between the mean levels in the high and low disease activity groups. Only levels of anti,Apo A-I were significantly higher in samples obtained from individual patients during disease flares than in samples obtained during disease quiescence. In the lupus nephritis patients, anti,Apo A-I and anti-HDL levels correlated with serum levels of high avidity IgG anti,double-stranded DNA. Conclusion Persistent disease activity is associated with a significant increase in IgG anti,Apo A-I and anti-HDL in patients with SLE. [source]

Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: The randomized, double-blind, phase ii/iii systemic lupus erythematosus evaluation of rituximab trial,

ARTHRITIS & RHEUMATISM, Issue 1 2010
Joan T. Merrill
Objective B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus (SLE), and rituximab induces depletion of B cells. The Exploratory Phase II/III SLE Evaluation of Rituximab (EXPLORER) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE. Methods Patients entered with ,1 British Isles Lupus Assessment Group (BILAG) A score or ,2 BILAG B scores despite background immunosuppressant therapy, which was continued during the trial. Prednisone was added and subsequently tapered. Patients were randomized at a ratio of 2:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. Results In the intent-to-treat analysis of 257 patients, background treatment was evenly distributed among azathioprine, mycophenolate mofetil, and methotrexate. Fifty-three percent of the patients had ,1 BILAG A score at entry, and 57% of the patients were categorized as being steroid dependent. No differences were observed between placebo and rituximab in the primary and secondary efficacy end points, including the BILAG-defined response, in terms of both area under the curve and landmark analyses. A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups. Safety and tolerability were similar in patients receiving placebo and those receiving rituximab. Conclusion The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse. No differences were noted between placebo and rituximab in the primary and secondary end points. Further evaluation of patient subsets, biomarkers, and exploratory outcome models may improve the design of future SLE clinical trials. [source]

Prospective analysis of treatment outcome and prognostic factors in patients with T-cell lymphomas treated by CEOP-B: single institutional study

BRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006
Hwa Jung Sung
Summary The important prognostic factors were evaluated for T-cell non-Hodgkin lymphoma (NHL) patients in a prospective study using the CEOP-B protocol [a modified cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)-like regimen that uses epirubicin instead of doxorubicin with the addition of bleomycin]. Fifty-two patients were enrolled in the study. The overall response rate was 63·5%. The median progression-free survival (PFS) and median overall survival (OS) was 18·0 and 39·5 months respectively. The most common toxicity was neutropenia. The factors related to poor outcome were a high International Prognostic Index (IPI) and a high ,B' score (bone marrow involvement, B symptoms, bulky disease). We developed a new prognostic model, namely the Prognostic Group for T cell NHL (PGT) that included four groups: PGT1 (low IPI/low B score), PGT2 (low IPI/high B score), PGT3 (high IPI/Low B score) and PGT4 (high IPI/Low B score). OS and PFS (not reached, 48 months) in the PGT1 group were significantly longer than those (11·5 and 4·8 months) in PGT2. The same result was observed in the PGT3 and PGT4 groups. The CEOP-B regimen was moderately active and tolerable for T-cell NHL patients, and the PGT system might be useful for the prediction of long-term survival of T-cell NHL patients. [source]