Introduction. The possibilities of modern therapy for systemic sclerosis (SSc) remains limited, since most of the used drugs do not have a diseasemodifying effect. This encourages the study of new approaches that potentially affect the fundamental pathological processes underlying the disease. One example is anti-B cell therapy, in particular rituximab (RTX). Until now RTX do not have a registration for the treatment of SSc, but there is a large positive experience of its use, which is reflected in recent meta-analyses and clinical recommendations. Complicated and expensive methods for obtaining genetically engineered biological preparations have contributed to the emergence of more accessible biosimilars, one of which is the RTX biosimilar, Acellbia (Biocad, Russian Federation). The “biosimilar” versions of RTX might reduce the cost of therapy and increase patients accessibility to this treatment option. The RTX biosimilar Acellbia (ACB) has received approval in Russian Federation in 2014 for all indications held by reference RTX (including rheumatoid arthritis and ANCA-associated vasculitis). The aim of this study was to investigate the efficacy and safety of Acellbia in patients with systemic sclerosis. Material and methods. Our prospective uncontrolled study included 20 patients (14 women) aged 50±14 years, with a disease duration of 3.5±2.7 years. Indications for the prescribing of ACB were high disease activity and the presence of risk factors for progression. All patients had radiological signs of interstitial lung disease, 13 (65%) were positive for antibodies to topoisomerase 1. None of the patients had previously been treated with biological therapy. All patients received glucocorticoids in low doses and 15 (75%) patients were not on concomitant immunosuppressants during the study. ACB was administered in doses of 2 g (two doses of 1 g with a weekly interval) at inclusion of the study and after 6–8 months according to the same scheme, cumulative dose – 4 g. An assessment of basic measurements was obtained at baseline (Point 0), before the second course (after 7.2±1.7 mo, Point 1) and at the end of follow-up (13.4±1.6 mo, Point 2). The results are presented in the form of mean values and standard deviations. Results. There was a positive effect on the main manifestations of the disease, which accompanied by stable depletion of CD19+ B lymphocytes in the peripheral blood. At the intermediate assessment (between points 0–1), no significant changes were observed, with the exception of the skin score. At the end of the study, most of the parameters showed a significant improvement between points 0–2. The activity of the disease (EScSG-AI) decreased, and the skin score decreased from 12.8±11 to 6.2±5.6 (p=0.002). The forced vital capacity (% of predicted) increased from 89±18.2 to 98.26±16.13% (p=0.0002), and the diffusion capacity of the lungs (% of predicted) increased from 56.8±15.7 to 61.9±17.2% (p<0.019). A significant decrease in CRP, antitopoisomerase-1 antibodies, as well as IgG (from 12.6±2.6 to 10.2±2.2 g/l) was noted. Repopulation to normal level of B lymphocytes did not occur in any case, and complete depletion of B lymphocytes at the end of the study was maintained in 83% of patients (15 of 18). The quality of life questionnaire SHAQ improved (p=0.0001), and the average dose of prednisolone was reduced from 11.0±2.7 to 9.4±2.3 mg/day (p=0.03). Positive changes according to HRCT was evident in 9 (45%) patients due to a decrease in ground glass opacity. The frequency and spectrum of adverse events (AEs) corresponded to those already known for RTX. Of the 20 patients who received 2 courses of ACB, two withdrew from the evaluation at Point 2 due to pregnancy (1) and lung cancer (1). A total of 11 (55%) AEs were reported in 9 (45%) patients, most of them were classified as mild. Infectious complications developed in 7 (35%) patients: respiratory infections of the upper respiratory tract (4), positivity in the TB skin test (2), otitis (1), cystitis (1) and cholecystitis (1). One patient developed calf vein thrombosis and lung cancer was diagnosed in one case. Conclusion. Our data suggest that Acellbia could be used for the treatment of SSc. A short-term, prospective, uncontrolled study showed good efficacy and acceptable safety of the ACB biosimilar in SSc. A significant decrease of skin fibrosis and improvement of lung functions have been proven. The clinical effect of ACB manifested by the 6th month from the start of therapy and reached its maximum one year after its initiation. Due to the positive efficacy of ACB, it can be prescribed for the patients with SSc with ineffectiveness and/or intolerance to immunosuppressants, and could be considered as a first-line therapy. Our data should be confirmed by the results of controlled clinical trials.

In systemic sclersis (SSc), different types of renal involvement occur. Their severity can range from asymptomatic deterioration of renal function to life-threatening damage, which is a complex therapeutic problem. Rituximab (RTM) has been used in the treatment of SSc and other autoimmune diseases with promising results, but its effect on renal function has not been adequately studied. Objective: to evaluate the renal function during complex therapy, including RTM, in patients with SSc over a long-term follow-up (at least 1 year). Material and methods. The study included 90 patients with SSc who were examined at least twice – before and 1–3.5 years after initiation of RTM treatment. Renal function was assessed by glomerular filtration rate (GFR) calculated according to the CKD-EPI formula. The stages of chronic kidney disease (CKD), blood pressure, daily proteinuria, skin score, activity, and indicators of lung function – forced vital capacity and diffusing capacity of the lungs – were also determined. Results and discussion. Against the background of complex therapy with RTM, there was a statistically significant decrease in GFR in the entire group of patients at the end of observation. On the other hand, renal function remained stable in the majority of patients with initially preserved GFR and there was a 25 % decrease – from 20 to 15 patients – in the number of patients with CKD. In more than half of the patients who initially had CKD, GFR increased (n = 11) or stabilized (n = 2) after therapy, and it decreased in a statistically insignificant manner in only 7 patients, whereas the development of a more advanced stage of CKD was observed in only 2 cases. The results of the treatment of 2 patients who had previously experienced scleroderma renal crisis (SRC) are reviewed in detail. Conclusion. In this study, there was no significant effect of RTM treatment on GFR and grade of CKD. Most patients had stable renal function; patients with an initial low grade of CKD showed a tendency toward stabilization of renal function. A significant decrease in GFR during long-term therapy noted in the entire patient group appears to be explained by an increase in renal insufficiency in patients with initially severe scleroderma renal damage, particularly due to SRC. Further studies on the effects of RTM therapy on renal function in patients with SSc are needed.

Autologous hematopoietic stem cell transplantation (auto-HSCT) is presently the only disease-modifying strategy for the treatment of systemic sclerosis (SSs) that has Level A evidence, the effectiveness of which has been proven in three controlled clinical trials: ASSIST, ASTIS, and SCOT. Despite the positive results obtained with the use of this treatment option, the issues related to its tolerability and safety remain unresolved. The complications caused by obvious immunosuppression and higher frequency of infections are the main causes of death after autoHSCT for autoimmune diseases and occur mainly in the first month after treatment. Overall, the studies performed confirm the overall assessment of auto-HSCT as an effective and relatively safe treatment for severe SSs.

The group of scleroderma diseases includes a number of clinical entities, the main symptom of which is skin tightening. Scleroderma is a prominent example of these diseases, characterized by excessive synthesis and deposition of collagen in organs and tissues. A patient with juvenile systemic scleroderma with induration of the skin and underlying tissues, and persistent contractures of large joints since childhood, is described. This clinical example illustrates disease course peculiarities and differential diagnosis of systemic and limited (focal) scleroderma and scleroderma-like conditions in pediatric patients. The feasibility of pathogenetic therapy aimed at improving patient's the quality of life with formed disease phenotype is shown.

The group of scleroderma diseases includes a number of clinical entities, the main symptom of which is skin tightening. Scleroderma is a prominent example of these diseases, characterized by excessive synthesis and deposition of collagen in organs and tissues. A patient with juvenile systemic scleroderma with induration of the skin and underlying tissues, and persistent contractures of large joints since childhood, is described. This clinical example illustrates disease course peculiarities and differential diagnosis of systemic and limited (focal) scleroderma and scleroderma-like conditions in pediatric patients. The feasibility of pathogenetic therapy aimed at improving patient's the quality of life with formed disease phenotype is shown.

Aimof the research – to determine the frequency of osteoporosis (OP) and to identify risk factors for a decrease in bone mineral density (BMD) in postmenopausal women with systemic sclerosis (SSс).Subjects and methods.The study included 113 postmenopausal women (median age – 60.0 [54.0; 63.0] years) with a reliable diagnosis of SSc according to the ACR/EULAR criteria (2013). The exclusion criterion was the presence of overlap syndromes. All women were interviewed according to a unified questionnaire, a laboratory and instrumental examination was conducted, including Dual-energy X-ray absorptiometry.Results. OP and osteopenia in at least one measurement area were diagnosed in 45.1% and 48.7% of women, respectively. Multivariate linear regression analysis revealed a negative effect of the total experience of taking glucocorticoids (GCs) on the value of BMD in the lumbar spine (b=–0.005; R2=0.136; p=0.017). Body mass index (BMI) (b=0.007; R2=0.208; p<0.001), glomerular filtration rate (GFR) (b=0.313; R2=0.213; p<0.001) is positive, and the cumulative dose of GCs (b=–0.269; R2=0.134; p<0.001), the duration of taking proton pump inhibitors (PPI) (b=–0.277; R2=0.291; p<0.001) and the duration of postmenopause (b=–0,223; R2=0.134; p<0.001) negatively affected the BMD of the femoral neck. BMD in the total hip (TH) was generally positively associated with BMI (b=0.493; R2=0.244; p<0.001), GFR (b=0.313; R2=0.150; p<0.001), 25-hydroxy calciferol level (b=0.273; R2=0.284; p=0.001), and negatively – with the cumulative dose of GCs (b=–0.219; R2=0.289; p<0.001).Conclusion. 93.8% of postmenopausal women with SSс had reduced BMD. Of the traditional risk factors, only BMI, the duration of postmenopause and the level of vitamin D had an impact on the state of BMD, and among the specific ones – the cumulative dose and duration of taking GCs, PPI and GFR.

Various clinical and immunological phenotypes of systemic sclerosis (SS) differ in the frequency and severity of manifestations of the disease, the progression of damage to internal organs, and prognosis. The detection rate of anti-U1-ribonucleoprotein (RNP) (anti-U1RNP) antibodies in SSD ranges from 5 to 30%. They are found in various rheumatic diseases (SS, systemic lupus erythematosus, rheumatoid arthritis, polymyositis, and Sjo gren’s syndrome) and are associated with a more favorable course, a good response to treatment (in particular, that with glucocorticoids), and a good prognosis. In SS, the clinical and laboratory associations of anti-U1RNP have been insufficiently investigated.Objective: to compare clinical, laboratory, and instrumental findings in patients with SS positive for anti-U1RNP, anti-topoisomerase-I (anti-Scl70), and anticentromere antibodies (ACA).Subjects and methods. Sixty-five anti-U1RNP antibody-positive patients were selected for a study group (Group 1) from the general database of patients who met the 2013 ACR/EULAR criteria for SS and who were followed up at the V.A. Nasonova Research Institute of Rheumatology in 2012 to 2017. The comparison groups included 50 anti-Scl70 antibody-positive patients with SS (Group 2) and 50 ACA-positive ones (Group 3). Anti-U1RNP negativity was confirmed in patients of the comparison groups.Results and discussion. Most patients in Groups 1 and 3 had the limited type of SS (88 and 94%, respectively) and a chronic course of the disease (82 and 94%) while Group 2 patients showed an acute and subacute course (52%) and predominantly the diffuse type of SS (58%). All the patients with SS had a higher level of antinuclear factor. The feature of the anti-U1RNP positive group was a preponderance of the limited type of the disease with minimal skin damage concurrent with a more frequent involvement of the musculoskeletal system (damages to the joints (65%) and muscles (43%), as well as with the high rate of damage to internal organs (in particular, the lung, heart, and gastrointestinal tract). The patients of this group exhibited high inflammatory and immunological activities, hematological disorders (hypocomplementemia (15%) and leukopenia (14%)). Sjo gren’s syndrome was detected in one-third of these patients.Conclusion. Further study of anti-U1RNP-positive SS will be able to create a management algorithm and to more clearly define the risks and prognosis of the disease for this group of patients.

In anti-U1-ribonucleoprotein (anti-U1-RNP) antibody positive patients with systemic scleroderma (SSD), the clinical picture and course of the disease have specific features: there is a preponderance of its limited form; inflammatory damage to the joints and muscles comes to the fore; and cutaneous manifestations are mild. Moreover, a high frequency (68%) of interstitial lung disease is found. At the same time, the autoimmune profile in this group has been little studied.Objective:to investigate the level of major autoantibodies (autoAbs) in anti-U1RNP antibody positive patients with SSD and to compare the frequency of the autoAbs in this group and in the groups of patients with SSD phenotypes associated with anti-centromere antibodies (ACA) and anti-topoisomerase I (anti-Scl70) antibodies.Patients and methods. The investigation enrolled a total of 144 patients meeting the 2013 ACR/EULAR SSD classification criteria. Forty-four anti-U1RNP antibody positive patients were found to have autoAbs, rheumatoid factor (RF), anti-cyclic citrullinated peptide (ACCP), anti-Ro, anti-La, anti-double-stranded DNA (anti-dsDNA), anti-Smith (anti-Sm), anti-cardiolipin (aCL), anti-histidyl tRNA synthetase (anti-Jo1), anti-Scl70, and anti-RNA polymerase III (anti-RNAP-III) antibodies, and ACA in two points. The study group (anti-U1RNP antibody positive patients with SSD) and the comparison groups (anti-Scl70 and ACA positive patients) were comparatively analyzed.Results and discussion. Anti-U1RNP antibody positive patients with SSD were commonly observed to have overlaps (34%) with rheumatoid arthritis and systemic lupus erythematosus, as well as concurrence with Sjögren’s syndrome (SS) (32.5%). The study group was found to have frequently RF (27%), anti-Ro (41%), anti-dsDNA (50%) antibodies, rarely anti-Sm (9%), ACCP (9%), anti-La (7%), ACA (11%), anti-Scl70 (9%), and aCL (2%) antibodies. Anti-Jo1 and anti-RNAP-III antibodies were not detected in any patient. SSD patients who were highly positive for anti-U1RNP antibodies (more than 2 upper limits of the reference range) significantly more frequently exhibited RF, anti-Ro and anti-dsDNA antibodies (p<0.01). Over time, anti-U1RNP antibodies detected at the onset of the disease persisted in 75% of patients. autoAbs were observed to disappear in patients with a low baseline titer of anti-U1RNP antibodies. Re-examination demonstrated that the detection rate of other autoAbs remained high in the group of patients who were highly positive for anti-U1RNP antibodies. Comparison of the three groups showed that the specific feature of the study group was the more frequent presence of other autoAbs, among which anti-Ro antibodies were most important. Their presence was associated with SS.Conclusion. In addition to clinical features, patients with SSD and anti-U1RNP antibody overproduction differ from those with major SSD phenotypes by the more frequent presence of other autoAbs. Persons who are highly positive for anti-U1RNP show the steady-state elevated levels of RF, anti-Ro and anti-dsDNA antibodies and the rare detection of SSD-specific autoAbs (ACA, anti-Scl70 and anti-RNAP-III).

Diffuse cutaneous systemic sclerosis (SSc) characterized by an acute, rapidly progressive course and severe damage to the internal organs has an unfavorable prognosis, while the treatment of this often fatal type of the disease has not been sufficiently developed. This paper reviews an update on an autologous hematopoietic stem cell transplantation (auto-HSCT) procedure, transplantation stages, and conditioning modes in patients with SSc. It presents the characteristics of auto-HSCT studies conducted in 2005 to 2016. The inclusion and exclusion criteria used in these studies are described and their outcomes compared. The results of three randomized controlled trials concerning auto-HSCT are analyzed separately. These findings confirm that auto-HSCT is currently more effective than standard immunosuppressive therapy. Auto-HSCT produces better results that can provide a more favorable long-term prognosis of SSc; it can prevent worsening of organ damages and improve skin scores and lung function. Patients with early diffuse SSc, a rapidly progressive course, and poor prognostic factors in the first 4–5 years of the disease before the development of functional insufficiency of the vital organs can be considered most promising for auto-HSCT.

Among the patients fulfilling the criteria for systemic sclerosis (SS), there is a subgroup without SS-specific antinuclear antibodies, but positive for anti-ribonucleoprotein (anti-U1 RNP) antibodies. The clinical significance of this type of antinuclear antibodies in SS is not clear. The presence of anti-U1 RNP antibodies is of great interest, since they are not only present in other rheumatic diseases, but are also considered as a marker for mixed connective tissue disease. Objective: to reveal the frequency of anti-U1RNP antibodies in patients with SS and to provide the clinical and laboratory characteristics of patients positive for these antibodies.Subjects and methods. 330 patients who fulfilled the 2013 ACR/EULAR criteria for SS and had been followed at the V.A. Nasonova Research Institute of Rheumatology from 2012 to 2017 were included. Anti-U1 RNP were determined by enzyme immunoassay (reference values: 0–25 U/ml).Results and discussion. Anti-U1RNP were detected in 65 (19.7%) patients with SS (85% of patients were highly positive; 15% were low-positive). The group included 8 men and 57 women; their mean age was 46±14 years. The disease duration was 11±7.9 years. Skin lesions were minimal; 59 (91%) patients had a limited form of the disease with swelling in the hands (scleredema) in 40% of cases and sclerodactyly in 60%. Raynaud's phenomenon was present in all the patients. One-half of the cases were observed to have peripheral ischemic disorders: digital scars and/or sores (43%), as well as necroses and ulcers of other sites, which were relatively rare (8%). Interstitial lung disease (ILD) was identified in 63% of cases. Elevated pulmonary artery systolic pressure (PASP) ≥40 mm Hg, as shown by echocardiography, was detected in 26% of cases and was associated mainly with the presence of ILD; pulmonary arterial hypertension was confirmed in three patients. Esophageal lesions were found in 61% of patients. One-third of patients had signs of scleroderma cardiopathy. The feature of the group was the common involvement of the locomotor system: joints with arthralgia and/or synovitis in 65% and muscles with mild and moderate myopathy in 43%. Erythrocyte sedimentation rate (ESR) and C-reactive protein levels were frequently elevated. The concurrence with Sjö gren's syndrome was common (in one-third of patients). None case of scleroderma renal disease was recorded; the mean values of kidney function were within the normal range; however, the glomerular filtration rate was lower than 80 ml/min/m2 in 17% of patients. All the patients were positive for antinuclear factor (HEp-2); in addition, there was rheumatoid factor (22%), antibodies against Ro/SS-A (41%), La/SS-B (18%), double-stranded DNA (42%), Scl70 (7%), and anticentromere antibodies (9%); 39 out of the 55 (71%) patients who were highly anti-U1 RNP-positive fulfilled the mixed connective tissue disease criteria proposed by R. Kasukawa et al. (1987).Conclusion. The investigation allows one to discuss of the presence of a special phenotype of SS, which is characterized by peculiar clinical manifestations in the presence of anti-U1 RNP overproduction.

The choice of drugs for the treatment of interstitial lung disease (ILD) associated with systemic sclerosis (SS) is currently very limited. Data from a number of studies show that rituximab (RTM) can improve lung function and reduce the severity of skin fibrosis in patients with SS.Objective: to evaluate the efficiency of RTM in a cohort of patients with SS-associated ILD after one-year follow-up. The indications for prescribing RTM were: 1) the inefficiency of standard therapy with glucocorticoids and immunosuppressants (ISs) or the impossibility of their use; 2) the early stage (first 3 years of the disease) with signs of poor prognosis, such as diffuse form, high skin scores (>14), male gender, rapid progression with a significant initial decline in forced vital capacity (FVC) and/or diffusion lung capacity (DLC), and a high anti-Scl-70 antibody positivity.Subjects and methods. The investigators selected a group of patients who had at least two assessment points at a 12-to-18 month interval (the mean follow-up period of 13±2 months) and took at least 1 g of RTM during this period. The investigation included 71 patients with a valid diagnosis of SS. Multi-slice spiral computed tomography (MSCT) revealed ILD in 90% of patients. The disease duration was 5.6±4.4 years. The presence of anti-Scl-70 antibodies was detected in 73% of patients. The mean cumulative dose of RTM was 1.43±0.6 g; 48 patients in Group 1 received ≤2 g of RTM (the mean dose, 1.1±0.1 g) and 23 patients in Group 2 took ≥2 g of RTM (mean dose, 2±0.6 g). Before starting treatment with RTM, all the patients received concomitant therapy with prednisone and 45% - with immunosuppressants.Results and discussion. The results assessed by a physician showed that good and moderate effects of the therapy were observed in 52 (73.2%) and 16 (22.6%) patients, respectively; no effect was seen in 3 (4.2%) patients. Overall, 95.8% of patients reported various degrees of improvement. There were significant changes as reductions in the disease activity index, skin scores, C-reactive protein and IgG levels, the number of patients with a high antinuclear antibody level, and the mean dose of prednisolone as well as increases in an oral aperture size, left ventricular ejection fraction, and 6-minute walk test scores. There were no changes in pulmonary artery systolic pressure and the HAQ DI. FVC increased from 77.35±19.9 to 82.6±20.7% (p=0.001). A minimal clinically significant increase in FVC ≥5% was noted in 41 (57.7%) people. The overall improvement in FVC (ΔFVC) reached 5.24%, while the changes were more significant in Group 2 (ΔFVC 8.98%) than in Group 1 (ΔFVC 3.75%; p=0.01). DLC remained stable, but there were significant group differences: ΔDLC was 3.75% in Group 2 and, conversely, decreased in Group 1 (1.6%; p=0005). The safety profile of the therapy was regarded as good and quite comparable with both the safety profile of ISs and the use of RTM in other trials. Infectious complications were recorded to be most common in 11 (15%) people. Of these, upper respiratory tract infections developed in 7 patients; plantar phlegmon occurred in one case; urinary tract infection and herpes zoster were detected in two and one cases, respectively.The results of this study confirm data from other studies that have demonstrated that RTM exerts a positive effect on SS-associated ILD. We were the first to show the association of positive changes in the measures of pulmonary function tests with the dose of RTM.

Легочная гипертензия (ЛГ) может развиваться при различных системных аутоиммунных ревматических заболеваниях (САРЗ), таких как системная склеродермия (ССД), системная красная волчанка, ревматоидный артрит, смешанное заболевание соединительной ткани. Наиболее часто у пациентов с САРЗ развивается ЛГ первой группы по классификации ВОЗ (легочная артериальная гипертензия, ассоциированная с системными заболеваниями соединительной ткани; ЛАГ-СЗСТ). Общая распространенность данной патологии составляет до 15 случаев на 1 миллион взрослого населения. Большинство случаев ЛАГ-СЗСТ обусловлено ССД. Выживаемость больных ЛАГ-СЗСТ в целом ниже, чем выживаемость пациентов с другими формами ЛАГ. Лечение любого САРЗ, в том числе и при развитии ЛАГ, предполагает использование комплексного подхода с применением глюкокортикоидов, болезнь-модифицирующих препаратов течения ревматического заболевания (циклофосфамид, метотрексат, азатиоприн и др.) и генно-инженерных биологических препаратов. Большинству пациентов с ЛАГ-СЗСТ показано назначение специфической таргетной терапии. Представитель нового класса (стимуляторы растворимой гуанилатциулазы (рГЦ)) риоцигуат одобрен для лечения ЛАГ. Препарат обладает уникальным двойным механизмом действия: (1) сенсибилизация рГЦ к эндогенному оксиду азота (NO) путем стабилизации связи NO-рГЦ; (2) прямая NO-независимая стимуляция рГЦ. Для больных СЗСТ-ЛАГ риоцигуат является основной альтернативой ингибиторам фосфодиэстеразы-5, как в качестве монотерапии, так и в качестве комбинированной терапии.

Установлено, что полиморфизмы генов медиаторов воспаления, тканевых матричных белков и ростовых факторов вовлечены в аутоиммунные и фибротические процессы при системной склеродермии (ССД). Хемокин CCL2 является ключевым воспалительным белком, присутствующим в циркулирующей крови и в очагах повреждения кожи больных ССД. Цель настоящего исследования состояла в изучении связи полиморфизма -2518 A/G гена CCL2 с уровнем С-реактивного белка (СРБ) у больных с разными клиническими и серологическими фенотипами ССД. В общей группе пациентов носители генотипа -2518АА имели статистически значимо более высокий средний уровень СРБ по сравнению с носителями аллеля -2518G (AG+GG генотипы) (р=0,032). Сходные различия уровней СРБ были получены у пациентов с диффузной формой ССД и у пациентов с позитивными титрами антител к топоизомеразе I (р=0,041 и р=0,042 соответственно). Выводы. Носительство генотипа -2518AА ассоциировано с высоким уровнем СРБ у больных с плохим прогнозом ССД (диффузная форма и позитивные титры аутоантител к топоизомеразе I) по сравнению с носительством аллеля -2518G. Полиморфизм -2518A/G гена CCL2 может быть использован в качестве генетического маркера тяжести и неблагоприятного прогноза ССД. It has been established that polymorphisms of inflammatory mediator genes, tissue matrix proteins and growth factors are involved in autoimmune and fibrotic processes in systemic scleroderma (SSc). CCL2 chemokine is a key inflammatory protein present in the circulating blood and in the lesions of the skin of patients with SSc. The purpose of this study was to study the association of the polymorphism -2518 A / G of the CCL2 gene with C-reactive protein (CRP) levels among patients with different clinical and serological phenotypes of SJS. In the general group of patients, carriers of the genotype -2518AA had a statistically significant higher average CRP level compared to carriers of the -2518G allele (AG + GG genotypes) (p = 0.032). Similar differences in CRP levels were obtained in patients with a diffuse form of SJS and in patients with positive antibody titers to topoisomerase I (p = 0.041 and p = 0.042, respectively). Conclusions: The carriage of the -2518AA genotype was significantly associated with a high level of CRP in patients with poor prognosis of SSc (presence of a diffuse form and seropositive autoantibody titers to topoisomerase I) compared with patients carrying the -2518G allele. Polymorphism -2518A / G of the CCL2 gene can be used as a genetic marker of severity and poor prognosis for SSc.

As of now, there are several pharmacological directions in the treatment and prevention of Raynaud’s syndrome and digital ulcers, including various vasoactive drugs (calcium channel blockers, intravenous prostanoids, endothelin receptor antagonists, phosphodiesterase 5 inhibitors, antiplatelets, and statins). The approach to treating systemic sclerosis-related digital ulcers is multifactorial: prevention of risk factors, local and systemic drug treatment, and surgical treatment if necessary.

Background Among patients, who meet the classification criteria for systemic sclerosis (SSc), there are the patients without specific SSc anti-nuclear antibodies and who are positive for antibodies to ribonucleoprotein (RNP). The clinical significance of the RNP antibodies in SSc is not clear. Objectives To investigate clinical and laboratory characteristics of SSc patients positive for antibodies to RNP. Methods The study included 52 patients (49 women and 3 men, mean age 44.2±15 years, median disease duration from the beginning of Raynaud's phenomenon 11.2±7years) who met the classification criteria of SSc (ACR/EULAR 2013) and have high level (>200 U/ml) of antibodies to RNP-70 (determined by ELISA, range 0–25 U/ml). Clinical, laboratory, and immunologic data were collected on all patients. Results All the patients met the criteria for classification of SSc ACR/EULAR 2013 (table 1). Other prevalent clinical manifestations were gastroesophageal reflux in 63, 5% of patients, joints involvement in 58%, myositis in 30, 7%, serositis in 27.5% (including 23% of pericarditis). All patients were positive for antinuclear factor (Hep-2) and in some cases RF, anti-SS-A, anti-SS-B, anti-Sm and anti-dsDNA antibodies were identified. The increased levels of CRP and/or ESR were found in 56% of cases. Among the SSc patients, there were 38 (73%) who satisfied for the classification criteria for mixed connective tissue disease (MCTD) proposed by Kasukawa et al. (1987).Table 1. Frequency of items of SSc classification criteria (ACR/EULAR 2013) in the group under study Items 52 patients Skin thickening of the fingers extending proximal to the metacarpophalangeal joints 9 (17,3%) Skin thickening of the fingers: 41 (78,8%)  puffy fingers 29 (55,7%)  sclerodactily 14 (27%) Fingertip lesions 22 (42,3%) Telangiectasia 25 (48%) Abnormal nailfold capillaries 45 (86,5%) Lung involvement: 37 (72%)  Pulmonary arterial hypertension 2 (4%)  Interstitial lung disease 35 (68%) Raynaud's phenomenon 52 (100%) SSc-related autoantibodies: 12 (23%)  ACA 4 (7,7%)  Anti-Scl-70 8 (15,4%) Conclusions In the group under study the limited form of SSc dominated, with high frequency of the different manifestations of vasculopathy, esophagus, joint and muscle disorders symptoms. A subtype of RNP-positive SSc patients often met the criteria for MCTD. This fact makes it reasonable to discuss the possibility of overlap-syndrome between these two diseases. Disclosure of Interest None declared

The FAS antigen (Apo-1/CD95) is a key molecule of apoptosis in most cell types, including activated immune cells and fibroblasts. The FAS gene promoter region contains a single-nucleotide polymorphism (-670A/G) associated with a substitution of the nucleotide arginine for guanine, which is associated with the predisposition to systemic lupus erythematosus, multiple sclerosis, sarcoidosis, and autoimmune hepatitis.Objective: to test the hypothesis that the FAS -670А/G polymorphism may predispose to systemic sclerosis (SS), its clinical and autoimmune phenotypes in a Russian patient sample.Subjects and methods. The instigation enrolled 90 SS patients who were classified according to clinical and autoimmune phenotypes. A control group consisted of 152 apparently healthy unrelated individuals matched for sex and age. The FAS -670А/G polymorphism was studied by polymerase chain reaction, followed by restriction fragment length polymorphism analysis.Results and discussion. A relatively small sample of Russian patients showed no statistically significant association of the studied FAS -670 A/G polymorphism with the predisposition to SS as a whole and the majority of its clinical and immunological phenotypes. There was a statistically significant positive association of the G allele (the FAS -670 GG+GA genotype) with the presence of digital ulcers and the chronic course of the disease. The G allele (the FAS -670 GG+ GA) was detected less frequently in patients with interstitial lung disease (ILD) than in those without ILD.Conclusion. The findings show that the FAS -670A>G polymorphism plays a role in the predisposition to some clinical phenotypes of SS in Russian patients.

Systemic sclerosis (SS) is a systemic disease, the basis for which is microcirculatory disorders, inflammation, and generalized fibrosis. Interstitial lung disease (ILD) is one of the primary manifestations of SS. Assessment of SS activity and severity is hindered as it is very difficult to differentiate fibrous and inflammatory changes that are mostly interrelated and have a similar picture.Objective: to estimate activity index (AI) and total severity index (TSI) for the follow-up of SS patients with different variants of ILD. Subjects and methods. The investigation enrolled 77 patients with SS and ILD, who were followed up at the V.A. Nasonova Research Institute of Rheumatology; their mean age at inclusion was 46±13 years. All the patients underwent high-resolution computed tomography (HRCT) of the chest and determination of TSI and AI scores at baseline and after an average of 59±12 months. According to the time course of HRCT revealed pulmonary changes over a 5-year follow-up, the patients were divided into 3 groups: 1) patients with improvement (n=16); 2) those without changes (n=39); 3) those with deterioration (n=22). The disease was regarded as active with AI scores of ≥3.Results and discussion. The mean AI scores for the entire patient cohort were low and substantially unchanged during the follow-up period, amounting to 2.1±1.55 and 2.37±1.55 (p > 0.05) at the start and at the end of the investigation, respectively. Following 5 years, only Group 3 showed AI scores of > 3. At inclusion, the groups did not differ in AI scores; however, 5 years later AI became significantly higher in Group 3 than that in Groups 1 and 2 (p = 0.004 and p=0.03, respectively). During the follow-up, TSI remained substantially unchanged and averaged 6.5±2.5 and 6.9±2.3 at inclusion and at the end of the investigation, respectively. Moreover, TSI tended to decline in Groups 1 and 2; but it significantly increased in Group 3 (p = 0.006) and at the end of the investigation it was significantly higher than that in Group 1 (p = 0.002). There was a direct correlation between AI and TSI in the total cohort of patients both at baseline and 5 years later (R = 0.57 and R = 0.53; p < 0.05). Direct correlations were found between the indices within Groups 2 (R = 0.51 and R = 0.37) and 3 (R = 0.67 and R = 0.71) at baseline and at the end of the follow-up, respectively; p < 0.05).Conclusion. In our investigation, AI and TSI reflected the course of ILD in patients with SS. ILD progression, as evidenced by HRCT, was followed by a significant increase in AI and TSI scores; they directly correlated between. Thus, AI and TSI may be used for monitoring progression of the disease.