Significance of the antigenic epitopes in heterogenous nuclear ribonucleoproteins-Ⅰfor the diagnosis and prognosis of systematic sclerosis

To assess the presence of autoantibodies against epitopes of heterogenous nuclear ribonucleoprotein- Ⅰ （hnRNP- Ⅰ ） in systematic sclerosis （SSc） and to analyze their clinical significance, polypeptides of hnRNP- Ⅰ were designed by biological technical software and analyzed with both the Wonderful Biology Information System and DNA Star-Protean Analysis Software at the same time. In these ways, two polypeptides of hnRNP- Ⅰ were obtained based on their amino acid sequences, folding features, hydrophilic, curl style, dough kneading sensation and the possibility on the surface of proteins. They are named as hnRNP- Ⅰ -1 （ NVKYNNDKSRDYTRPDLPSGDSQPSLDQT, 264-292 aa） and hnRNP- Ⅰ -2 （QLP4REGQEDQGLTKDYGNSOL, 441-461 aa）, simply designated as Ⅰ -1 and Ⅰ -2. The autoantibodies against hnRNPs were detected by means of ELISA using the synthetic epitopes polypeptides as antigen. It was found that the positive rate of detection for anti- Ⅰ -1 and anti- Ⅰ -2 autoantibodies were rather higher in SSc patients than that in other CTDs and the sensitivities and specificities of the testing with ELISA for anti- Ⅰ -1 and anti- Ⅰ -2 antibodies in SSc patients were 47.62%/93.43% and 38.1%/ 91.08%, without any significant difference between these two groups of testings. Also, there was no significant difference in the clinical features and laboratory findings, such as age, involvements in digestive and respiratory tracts and erythrocyte sedimentation rate etc., between the anti- Ⅰ -Ⅰ-positive and -negative groups in SSc patients. However, the hnRNP- Ⅰ -autoantibody-positive group of patients had obviously shorter duration of disease course compared with that of the autoantibody-negative group. Anti- Ⅰ -1 and anti- Ⅰ -2 autoantibodies also had no association with antinuclear antibody, anti-Sc170 and anti-centromere antibody （ACA） in SSc patients. So, it is apparent that the autoantibodies related with SSc may act through different pathways in the pathogenesis of SSc, and the hnRNP- Ⅰ autoantibody is a new type antibody occuring during the early stage of disease and appearing to have diagnostic and prognostic significances.

Leflunomide,a new disease-modifying drug for treating active rheumatoid arthritis in methotrexate-controlled phase Ⅱ clinical trial

Objective To evaluate the efficacy and safety of leflunomide in comparison with methotrexate (MTX) on patients with rheumatoid arthritis (RA) in China.Methods Five hundred and sixty-six patients with active rheumatoid arthritis were randomly assigned to receive leflunomide at 20 mg once daily or MTX at 15 mg once weekly in a controlled trial. Five hundred and four patients completed the 12-week treatment and some patients continued the treatment for 24 weeks. Results Both leflunomide and MTX could improve the symptoms,signs,and joint function,but there were no changes in X-ray observations of patients with rheumatoid arthritis. In the leflunomide group,the overall rates of effectiveness at 12 weeks and 24 weeks were 86.94% and 92.31% respectively; the rates of remarkable improvement were 64.95% and 79.81% respectively. In the MTX group,the overall rates of effectiveness at 12 weeks and 24 weeks were 84.04% and 83.15% respectively; the rates of remarkable improvement were 56.81% and 75.28% respectively. According to intent-to-treat analysis,the ACR 20% response rates at 12 weeks and 24 weeks in the leflunomide group were 62.54% and 67.18% respectively,compared with 60.08% and 61.32% respectively in MTX group. No statistical differences were shown in the efficacy between the two groups ( P >0.05). The adverse events in the leflunomide group were gastrointestinal symptoms,skin rash,alopecia,nervous system symptoms,decreased leukocyte count,and elevation of alanine aminotransferase (ALT). Most of these side effects were mild and transient. The incidence of adverse events in the leflunomide group was 16.84%,significantly lower than that in MTX group (28.17%,P =0.002).Conclusions Leflunomide is effective in the treatment of RA with less adverse events than MTX. Its efficacy is similar to MTX,but the incidence of adverse events and the rate of withdrawal due to adverse events were lower in the leflunomide group than in MTX group.