Anti-C1q antibodies antedate patent active glomerulonephritis in patients with systemic lupus erythematosus.

INTRODUCTION: Autoantibodies against C1q correlate with lupus nephritis. We compared titers of anti-C1q and anti-dsDNA in 70 systemic lupus erythematosus patients with (n = 15) or without (n = 55) subsequent biopsy-proven lupus nephritis. METHODS: The 15 patients with subsequent lupus nephritis had anti-C1q assays during clinical flares (mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), 10.0 +/- 4.7; range, 3 to 22) before the diagnosis of lupus nephritis (median, 24 months; range 3 to 192). Among the 55 others, 33 patients had active lupus (mean SLEDAI, 10.3 +/- 6.2; range, 4 to 30) without renal disease during follow-up (median 13 years; range 2 to 17 years) and 22 had inactive lupus (mean SLEDAI, 0; range, 0 to 3). RESULTS: Anti-C1q titers were elevated in 15/15 (100%) patients who subsequently developed nephritis (class IV, n = 14; class V, n = 1) and in 15/33 (45%) patients without renal disease (P < 0.001). The median anti-C1q titer differed significantly between the groups (P = 0.003). Anti-C1q titers were persistently positive at the time of glomerulonephritis diagnosis in 70% (7/10) of patients, with no difference in titers compared with pre-nephritis values (median, 147 U/ml; interquartile range (IQR), 69 to 213 versus 116 U/ml; 50 to 284, respectively). Titers decreased after 6 months' treatment with immunosuppressive drugs and corticosteroids (median, 76 U/ml; IQR, 33 to 106) but remained above normal in 6/8 (75%) patients. Anti-dsDNA antibodies were increased in 14/15 (93.3%) patients with subsequent nephritis and 24/33 (72.7%) patients without nephritis (P = ns). Anti-C1q did not correlate with anti-dsDNA or the SLEDAI in either group. CONCLUSIONS: Anti-C1q elevation had 50% positive predictive value (15/30) and 100% (18/18) negative predictive value for subsequent class IV or V lupus nephritis.

Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis.

OBJECTIVE: To investigate the specificities of antinuclear antibodies (ANA) associated with systemic sclerosis (SSc) disease classification and internal organ involvement among patients with SSc of different origins (European and American). METHODS: Serum samples from 374 adult patients diagnosed with SSc were studied: 127 French patients (Paris) were compared with 247 US patients (Pittsburgh). Patients were classified into diffuse cutaneous (dc) and limited cutaneous (lc) SSc subsets. Antibodies associated with SSc were determined by protein and/or RNA immunoprecipitation, indirect immunofluorescence, and immunodiffusion. RESULTS: SSc classification differed significantly in the 2 cohorts: lcSSc and overlap patients with lcSSc combined made up 76% of the French series versus 52% of the US group (p < 0.0001). The frequency of anti-RNA polymerase III antibody was significantly increased in US patients compared with French patients (p < 0.0001). The frequency of anti-topoisomerase I (topo I) antibody was significantly increased among French patients (p < 0.0048). Anti-topo I-positive French SSc patients were less likely to have dcSSc (38% vs 65%) and more likely to have milder disease than US anti-topo I-positive patients. The French dcSSc patients had lower proportions of joint/tendon manifestations and renal crisis (7% vs 17%), but more often had radiographic evidence of pulmonary fibrosis (57% vs 30%). French lcSSc patients had a lower frequency of pulmonary arterial hypertension than US lcSSc patients (9% vs 31%; p = 0.002). CONCLUSION: There are disease classification and SSc-related serum autoantibody differences between French and American patients with SSc. These differences help to explain variations in clinical features reported from different geographic regions.

Lumiracoxib does not affect methotrexate pharmacokinetics in rheumatoid arthritis patients.

BACKGROUND: Methotrexate and nonsteroidal antiinflammatory drugs are frequently coadministered in the treatment of rheumatoid arthritis (RA). OBJECTIVE: To evaluate the effect of lumiracoxib, a novel cyclooxygenase-2 selective inhibitor, on methotrexate pharmacokinetics and short-term safety in patients with RA. METHODS: This multicenter, randomized, double-blind, placebo-controlled crossover study enrolled 18 patients (mean age 49.1 y) with stable RA. Patients were randomized to receive methotrexate 7.5-15 mg orally once weekly plus either lumiracoxib 400 mg/day or placebo for 7 days. Patients then received the other treatment combination for an additional 7 days. Serial blood and urine were collected for 24 hours after the methotrexate dose on day 1 (methotrexate alone) and days 8 and 15 (combination treatment). RESULTS: Plasma methotrexate pharmacokinetics (AUC(0-t), maximum concentration [C(max)], time to C(max)) and methotrexate protein binding were similar for methotrexate alone (108.0 ng.h/mL, 26.7 ng/mL, 1.5 h, and 57.1%, respectively), methotrexate/lumiracoxib (110.2 ng.h/mL, 27.5 ng/mL, 1.0 h, and 53.7%, respectively), and methotrexate/placebo (101.8 ng.h/mL, 22.6 ng/mL, 1.0 h, and 57.0%, respectively). Similarly, no clinically significant difference was found in the urinary excretion of methotrexate. Mean exposure to the 7-OH metabolite was lower when methotrexate was given with lumiracoxib compared with placebo, shown by a reduction in AUC and C(max), although similar amounts of the metabolite were recovered in urine following both lumiracoxib and placebo. Coadministration of methotrexate and lumiracoxib was well tolerated. CONCLUSIONS: Lumiracoxib had no significant effect on the pharmacokinetics, protein binding, or urinary excretion of coadministered methotrexate in patients with RA.