Системная склеродермия (ССД) харак-теризуется чрезмерным фиброзообразовани-ем, микроангиопатией и наличием циркули-рующих антител к различным аутоантигенам.Патогенез ССД до сих пор полностью не изу-чен. В частности, остается не до конца выяс-ненной роль аутоиммунитета в развитии кли-нико-патогенетических фенотипов. 418Научно-практическая ревматология. 2016(54)4:418-423 О р и г и н а л ь н ы е и с с л е д о в а н и я Objective: to estimate frequency of autoantibodies in a cohort of Russian patients with systemic sclerosis (SS) and to investigate clinical associations of these autoantibodies. Subjects and methods. In 2012 to 2015, the investigation enrolled 300 patients (58 men and 242 women) who fulfilled the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) SS criteria. All patients underwent immunological examination including determination of antinuclear antibodies, anti-topoisomerase I (anti-Scl-70) antibodies, anti-centromere antibodies (ACA), anti-U1-ribonucleoprotein antibodies (anti-U1 RNP), and anti-RNP III antibodies. Results and discussion. The vast majority of patients were middle-aged females with moderate disease duration. There was a preponderance of patients with limited cutaneous form (55.3%); 37.4% patients had diffuse SS; 5.9% had overlap syndrome; and <1% had visceral and juvenile SS. The vast majority (83.8%) of patients were found to have antinuclear factor. Among the SS-associated antibodies, anti-Scl-70 were most common and were revealed in approximately one-half of the patients. ACA was present in only 44 (14.6%) patients. There was a combination of positivity for ACA and anti-Scl-70 antibodies in 3 patients with limited cutaneous SS, including one with an early form of the disease. 26 patients had anti-U1 RNP antibodies. Among them, there was a preponderance of patients with limited cutaneous SS and overlap syndrome. Anti-RNP III antibodies were found in 5.5% of cases, mainly in those with limited cutaneous SS; these were observed in one patient with diffuse SS and interstitial lung disease. No kidney injury was seen in this patient group. Conclusion. The characteristics of the Russian cohort are the preponderance of the limited cutaneous SS and the frequent detection of anti-Scl-70 antibodies in both diffuse and limited cutaneous SS; no correlation of anti-Scl-70 antibodies with rapid progression of the pathological process, with kidney disease. PROFILE OF AUTOANTIBODIES IN SYSTEMIC SCLEROSIS

BackgroundCyclophosphamide (CyP) is considered as a drug of choice for the treatment of interstitial lung disease (ILD) in the patients with systemic sclerosis (SSc). However, according to the literature, the use of CyP leads to rather limited and transient improvement of the pulmonary fibrosis. In this context the search for novel, more efficacious agents has been continued, such as attracting much attention retuximab (RTM).ObjectivesTo compare the impact of CyP and RTM on SSc clinical manifestation and activity, and the safety of these agents in the open-label prospective non-randomized study.Methods107 patients with the confirmed SSc diagnosis and ILD evidence based on HRCT findings were enrolled into the study. All patients received low-dose and moderate-dose prednisolone regimens. 36 patients (Group A) received parenteral CyP for 12±6 months at total dose 10.6±5 g (the average age 47±12 years, females 92%, SSc duration 5.0±4.8 years, diffused/localized forms 1.6/1). 71 patients (Group B) received RTM at total dose 1.43±0.66 g over the follow-up period 13.2±2 months (the average age 46±13 years, females 83%, SSc duration 5.6±4.4 years, diffused/localized forms 1.4/1); to 32 (45%) of them RTM was added to immunosupressants due to inadequate efficacy of the latter. The time courses FVC(%), modified skin count (mRss, points), activity index (EScSG, points), left ventricle ejection fraction (LVEF,%), mean pulmonary arterial pressure (EchoCG), and cardiac rhythm and conductivity disorders (ECG) were evaluated.ResultsIn Groups A and B the therapy was associated with significant decrease in mRss (p=0.009 and 0,001, respectively) and EScSG (p=0.000165 and 0.001, respectively). Increase in LVEF (61.8±7.3 и 63.6±7.3. p=0.02) was observed only in RTM-treated patients.Evaluation of FVC time course in Groups A and B revealed significant FVC increase (p= 0.034 and 0.000045, respectively), with median increment about 5%.In Group A FVC 10% FVC increase was found in the third of the patients thus exceeding respective parameter in Group B (p=0.2). The patient percentage with FVC decrease by ≥10% was similar in both groups.During the follow-up period no change of the other studied parameters was observed.The therapy was better tolerated in RTM-treated group: during RTM therapy adverse reactions emerged in significantly lower proportion of the patients (11/14%) compared with CyP-treated group (19/53%), p=0,0000.ParametersGroup AGroup BEScSG 1M ± SD 2.8±2*2.8±1.8*EScSG 2M ± SD 1.4±1.17*1.3±1.1*mRss 1M ± SD 11.2±9.8 *11.3±9.6 *mRss 2M ± SD 7.9±6.8. *8.0±6.6*FVC 1M ± SD 80.5±20.1* 77.3+20 *FVC 2M ± SD 85.9±20.5*82.6+21.*Δ FVC%5.4[-0.6; 12.3]5.3[0.1; 10.2]FVC increment by ≥10%, n/%11/3114/19.7FVC decrement by ≥10% n/%2/5.64/5.6Notes:in Parameters column 1 = before treatment, 2 = after treatment; M ± SD = mean value and standard deviation; * = significant difference between the vales measured before and after the treatmentConclusionBoth agents effectively alleviated skin induration and EScSG, and significantly improved FVC. However, C...

О р и г и н а л ь н ы е и с с л е д о в а н и я ФГБНУ «Научноисследовательский институт ревматологии им. В.А. Насоновой»,

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Background:A sound experience has been accumulated up to date with the use of rituximab (RTХ) for treatment of systemic sclerosis (SSc). Some studies reported improvement of skin fibrosis following treatment with RTХ, but long-term follow-ups are really few.Objectives:to evaluate the effect of RTХ on the manifestations of skin fibrosis in patients (pts) with SSc in the long-term follow-up.Methods:This prospective study included 71 pts aged 46 years (17-66) on average, 59 (83%) pts were females, mean disease duration was 5,6±4,4 years, and mean follow-up - 42 months (12-72) (mo). Diffuse SSc was established in 42 (59%) pts. All pts received glucocorticoids in low doses. 45% of pts were receiving immunosuppressants at study entry. The following parameters were evaluated: Rodnan skin score (mRSS), interdigital space(IDS) (the distance between the tips of 1 and 5 fingers at maximum extension), oral aperture (OAp) and activity index (EScSG-AI) over the periods: 12-18 mo, 24-30 mo, 36-42 mo, 48-54 mo and 60-72 mo after initiation of RTX therapy. The results are presented as: mean values, delta (Δ), median, upper and lower quartiles.Results:RTX therapy resulted in significant decrease of disease activity index, which statistically significantly correlated with decrease of mRSS - the main indicator of the severity of skin fibrosis (r=0,39;p=0,001). Changes in parameters by follow-up periods are presented in the Table 1.Table 1.Changes in clinical and instrumental parameters at RTX treatment (delta; median; lower quartile; upper quartile).Parameters12-18 mo (n=71)24-30 mo (n=55)36-42 mo (n=36)48-54 mo (n=24)60-72 mo (n=17)ΔmRSS3,32 [3.3; 0; 8]5,4 [3; 0; 10]5,1 [3,5; 0; 9]5,3 [3; 0; 10]7,3 [5; 1; 14]p=0,001p=0,001p=0,001p=0,001p=0,001ΔOAp, cm0,24 [0,1; 0; 0,5]0,26 [0,1; 0; 0,6]0,39 [0,2; 0; 0,8]0,31 [0.3; 0; 0,7]0,36 [0,2; 0; 0,8]p=0,0009p=0,0006p=0,004p=0,006p=0,009ΔActivity index (EScSG-AI)1,49 [1,5; 0; 2,5]1,64 [1,5; 0; 2,5]1,11 [1; 0; 2]2 [2; 1; 3]2,17 [2; 1,5; 2]p=0,001p=0,001p=0,0001p=0,0001p=0,0001Cumulative dose of RTX, g1,43±0,62,97±0,83,45±1,33,96±1,15,15±1,7Decreasing of mRSS statistically significantly correlated with increasing cumulative dose of RTX (r=0,29;p=0,01). Decreasing disease activity index correlated with increasing cumulative dose of RTX (r=-0,37; p=0,01). IDS improvement was documented at all assessment time periods, although statistically insignificant.Conclusion:The results of this study confirm reported positive effect of RTX on the reduction of skin fibrosis in SSc. Long-term follow-up demonstrated steadily decreasing skin fibrosis and improvement of microstomia with increasing oral aperture in parallel with a decrease of the disease activity index and increasing cumulative dose of RTX.Disclosure of Interests:None declared