Different Clinical Relevance of Anti-Citrullinated Protein Antibodies in RA Patients.

The objective of the study was to find a potential relationship between ACPAs and disease activity, bone destruction, and ACPA responses to various therapeutic regimens. The study included 232 patients with rheumatoid arthritis (RA); 90 patients had early RA, and 142 patients had an advanced stage of the disease. 77 (85.6%) patients with early RA were highly positive for anti-CCP, and 29 (70.7%) patients were highly positive for anti-MCV. A positive correlation was found between anti-MCV and DAS28 (r = 0.4; p = 0.04). As for advanced RA, 78 (80.4%) patients were high-positive for anti-CCP, and 70 (79.5%) were high-positive for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r = 0.4; p = 0.02), as well as CDAI (r = 0.4; p = 0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0-122.0)) were found in pts highl-positive for anti-MCV (n = 79), compared to low-positive/negative (n = 27) patients (57.0 (31.0-88.0); p < 0.05). Anti-MCV levels dropped significantly in pts on rituximab and tocilizumab therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment. Anti-MCV levels correlated with inflammatory activity and development of bone destruction and decreased in pts on treatment. Anti-CCP was less responsive and showed minor changes during treatment; therefore, its thorough monitoring was not feasible.

Anti-topoisomerase 1 Antibody Level Changes after B Cell Depletion Therapy in Systemic Sclerosis.

The aim of our study was to assess the relationship between the changes of antinuclear autoantibodies (ANAs) and autoantibodies to topoisomerase 1 (anti-Topo 1) in systemic sclerosis (SSs) patients on rituximab (RTX) therapy. The prospective study included 88 patients (73 women) with a mean age of 47 (17-71) years. The mean disease duration was 5.9 ± 4.8 years. The mean follow-up period was more than 2 years (27 (12-42) months). We documented a statistically significant change in skin score, the disease activity index, improvement of pulmonary function and reduction of mean dose of prednisolone after RTX treatment. There was a significant decrease in the number of patients with high levels of ANA and overall decrease of the ANA and anti-Topo 1 levels. A moderate positive statistically significant correlation was found between ANA and anti-Topo 1 (r = 0.403). In the group of patients positive for anti-Topo 1 there were a more pronounced depletion of B lymphocytes, significantly higher increase in forced vital capacity and diffusion capacity, decrease in the disease activity index, compared with patients negative for anti-Topo 1. We observed the decline in the level of ANA and anti-Topo 1 in SSc patients after RTX therapy, and it was correlated by an improvement of the main outcome parameters of the disease. Therefore, anti-Topo 1 positivity could be considered as a predictor of a better response to RTX treatment, especially in SSc patients with hyperproduction of anti-Topo 1.

Global Antiphospholipid Syndrome Score (GAPSS) in Patients with Systemic Lupus Erythematosus.

The Global Antiphospholipid Syndrome Score (GAPSS) is a tool proposed to quantify the risk of clinical manifestations associated with antiphospholipid antibodies (aPL) and certain cardiovascular risk factors. To validate GAPSS in a cohort of patients with systemic lupus erythematosus in Russia. 115 patients with SLE were included in the study, including 51 (44%) patients with systemic lupus erythematosus (SLE) with antiphospholipid syndrome (APS), 14 (12%) SLE patients with aPL, and 50 (44%) patients with SLE. There was a history of thrombosis in 58 (50%) out of 115 patients; of them, 14 (24%) had arterial thrombosis, 29 (50%) had venous thrombosis, and 15 (26%) had combined thrombosis. Pregnancy against the background of the disease occurred in 43 women included in the study. Of them, 29 (67%) had obstetric pathology. Patients with thrombosis and obstetric pathology had a GAPSS score of 7.17 ± 5.64 versus 4.48 ± 4.55 without these manifestations (p = 0.0003). There was a significant association between GAPSS levels and thrombosis: patients with thrombosis had a GAPSS of 7.31 ± 5.70, those without thrombosis-4.00 ± 4.81 (p = 0.001). GAPPS values were higher in arterial thrombosis compared to venous thrombosis (10.40 ± 25.30 versus 5.82 ± 5.28, p = 0.01). GAPSS levels  ≥ 6 and  ≥10 were analyzed to select GAPSS values at which a high risk of recurrent thrombosis and/or obstetric pathology could be indicated. All GAPSS levels had a significant association with clinical manifestations of APS. The quality of GAPSS by ROC analysis showed an area under the curve (AUC) for GAPSS of 0.697. GAPSS can be used to assess the risk of recurrence or development of thrombosis and/or obstetric pathology in patients with SLE in the Russian Federation. The GAPSS ≥6 values should be used to stratify patients with SLE into high risk group for recurrence of vascular complications. Further prospective follow-up is needed to confirm the value of GAPSS.

Antibodies to Domain I ß2-Glycoprotein 1 in Patients with Antiphospholipid Syndrome and Systemic Lupus Erythematosus.

The role of antiphospholipid antibodies (aPL), which are not included in the Sydney diagnostic criteria, in antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) is poorly understood. The aim of this study was to determine the clinical significance of IgG antibodies for domain 1 of ß2-glycoprotein 1 (ß2-GP1), IgG anti-ß2-GP1DI, in patients with APS with and without SLE. The study included 187 patients with APS with or without SLE, 49 patients formed the comparison group, and 100 apparently healthy individuals formed the control group. IgG/IgM antibodies to cardiolipin (aCL) and IgG/IgM anti-ß2-GP1 were determined by enzyme immunoassay (ELISA) in patients with or without APS, and IgG anti-ß2-GP1DI was determined by chemiluminescence assay (CLA) in all patients and controls. IgG anti-ß2-GP1DI was detected in 37 (71%) of 52 patients with primary APS (PAPS), in 6 (50%) of 12 patients with probable APS, in 42 (71%) of 59 patients with SLE + APS, in 17 (26%) of 64 patients with SLE, in 1 (2%) of the comparison group, and in none of the control group. IgG anti-ß2-GP1DI was significantly associated with PAPS and SLE + APS compared with the patients with SLE (p = 0.0002 and 0.0001, respectively). The association of IgG anti-ß2-GP1DI with clinical manifestations of APS (thrombosis (p = 0.001) and obstetric pathology (p = 0.04)) was detected. There was a significant association of IgG anti-ß2-GP1DI with arterial thrombosis (p = 0.002) and with late gestational obstetric pathology (p = 0.01). High specificity of IgG anti-ß2-GP1DI depending on the diagnosis and clinical manifestations of APS despite low sensitivity was noted: specificity was 84% for thrombosis, 94% for obstetric pathology, and 89% for APS. Isolated IgG anti-ß2-GP1DI positivity was reported in 2% of 50 aPL-negative patients and was not associated with APS manifestations. The frequency of IgG anti-ß2-GP1DI detection was higher in the patients with APS compared to the patients with SLE, comparison group, and control (p < 0.05). Positive IgG anti-ß2-GP1DI values were significantly associated with thrombotic complications and with obstetric pathology (p = 0.002 and p = 0.01, respectively). Specificity of IgG anti-ß2-GP1DI for APS and its clinical manifestations (thrombosis and obstetric pathology) was higher than sensitivity (89, 94, and 84%, respectively).

[Antibodies to the phosphatidylserine/prothrombin complex in the diagnosis of antiphospholipid syndrome].

AIM: To determine the significance of antibodies to the phosphatidylserine/prothrombin complex (aPS/PT) in patients with systemic lupus erythematosus (SLE) antiphospholipid syndrome (APS). MATERIALS AND METHODS: A total of 190 patients were included in the study: 123 (64.7%) with reliable SLE and 55 (29%) with PAPS. The control group included 100 relatively healthy subjects of comparable age. All patients were tested for classical aPL as well as IgG/IgM-anti-PS/PT by enzyme immunoassay. RESULTS: Based on the average values of IgG/IgM aPS/PT of the control group, the levels of positivity were allocated mean (M) + 3 or 5 standard deviations (SD): M+3SD and M+5SD. IgG aPS/PT levels above 73.6 U/ml (M+5SD) were more accurate diagnostic, for IgM aPS/PT above 18.0 U/ml. IgG-aPS/PT were detected in 84 (44%) of 190 patients. Levels above diagnostic levels were detected in 68 (65%) of 104 patients with APS (55 with PAPS and 59 with SLE+APS). Thrombosis was significantly more common in patients with IgG aPS/PT compared with patients negative for IgG aPS/PT. Arterial but not venous thrombosis was associated with IgG aPS/PT positivity. CONCLUSION: The frequency of detection of IgG aPS/PT in the examined patients was 44%, IgM aPS/PT 29% and their combination 19% of 190 patients. Half of the patients with probable APS had positive IgG aPS/PT and third IgM aPS/PT. Median IgG aPS/PT were significantly higher in patients with APS compared to patients without APS and the control group. Thrombosis was associated with IgG aPS/PT. Arterial thrombosis was significantly more frequently reported in patients with IgG aPS/PT. The sensitivity of IgG aPS/PT for reliable APS at levels greater than 73.6 units/ml was 59%, specificity 92%, for IgM aPS/PT 35% and 91%, respectively.

Study of antiphospholipid antibodies by enzyme immunoassay and chemiluminescent methods in patients with antiphospholipid syndrome and systemic lupus erythematosus (preliminary data).

Antiphospholipid antibodies (aPL) are a family of different autoantibodies that lead to recurrent vascular thrombosis of any localization and caliber, and/or obstetric pathology - fetal loss. Serological markers of antiphospholipid syndrome (APS) include only three types of aPL - lupus anticoagulant (VA), antibodies to cardiolipin (aCL) classes IgG and IgM, antibodies to ß2-glycoprotein1 (aß2GP1) classes IgG and IgM. Medium and high levels of aCL and aß2HP1 (IgG and / or IgM) were selected as serological markers of APS in the 2006 classification criteria. However, the threshold of values used from low to moderately high levels has not been standardized. aPL standardization issues are still unresolved, resulting in heterogeneous results of the ongoing studies. The aim of the study was to assess the comparability IgG/IgM-aCL and IgG/IgM-ab2GP1 by enzyme-linked immunosorbent assay and chemiluminescent analysis in patients with APS with and without (systemic lupus erythematosus) SLE. The study included 70 patients (49 women and 21 men) with APS, of which 21 (30%) were with primary APS (pAPS) and 49 (70%) with APS in combination with SLE. All study participants underwent determination of IgG/IgM-aCL and IgG/IgM-aß2GP1 by enzyme-linked immunosorbent. A study was performed by the chemiluminescent analysis: IgG/IgM-aCL - in 70 patients; IgG/IgM-aß2GP1 - in 69 patients. Results. According to preliminary data, the determination of IgG-aCL and IgG-aß2GP1 by the chemiluminescent analysis is informative in assessing positivity according to the manufacturer, compared with the enzyme-linked immunosorbent (p < 0.05). However, when taking into account the levels of antibody positivity determined by enzyme-linked immunosorbent, the level of positive values according to chemiluminescent analysis was much higher than the performance of the manufacturer.

[Vitamin D status in women with rheumatoid arthritis: frequency of hypovitaminosis, associations with disease activity, body composition and comorbidity].

AIM: To evaluate the status of vitamin D in women with rheumatoid arthritis (RA) and establish its associations with comorbidity, disease activity, and body composition components. MATERIALS AND METHODS: 86 women with RA (average age 58.18.5 years) were enrolled in the study. We analyzed the relationship of vitamin D levels with clinical and laboratory parameters and with the results of two-energy x-ray absorptiometry. MannWhitney or KruskalWallis, 2 and Spearman tests were performed using Statistica for Windows 10.0 (StatSoft Inc., USA). RESULTS: Vitamin D level was 22.4 [17.8; 27.3] ng/ml: deficiency was detected in 33%, and insufficiency in 46% of women with RA. Only 41% of patients with low vitamin D levels received supplements of cholecalciferol, while only 9% in a sufficient dose. 25(OH)D level was significantly lower in RA patients with sarcopenia, obesity, high activity according to DAS28 and in those who did not receive vitamin D supplements. There werent differences in 25(OH)D levels among subgroups of patient according to age, fertility, BMD status, comorbidity index, RA duration, ESR and CRP levels, medical therapy performed. CONCLUSION: 79% of patients with RA had low levels of vitamin D, while less than half of them received additional cholecalciferol supplements. Low vitamin D levels in RA patients were associated with high disease activity, sarcopenia, and obesity.

[The role of laboratory biomarkers in monitoring of rituximab biosimilar therapy (Acellbia, "BIOCAD") in patients with rheumatoid arthritis].

AIM: to evaluate the role of laboratory biomarkers in monitoring effectiveness of rituximab (RTM) biosimilar therapy in a total dose of 1200 mg. MATERIALS AND METHODS: 20 patients (pts) with rheumatoid arthritis (RA) (18 woman, mean age 61.5(54-66.5) years, mean disease duration 39.5(20-84) months, mean DAS28 5.6(4.9-6.8)) received two intravenous RTM biosimilar infusions (600 mg №2) in combination with DMARDs and glucocorticoids. Laboratory biomarkers were assessed at baseline and weeks 12 and 24 after the first infusion of RTX. RESULTS: RTM biosimilar induced decreases in DAS28, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) at week 12 and 24, p.

[Relationship between matrix metalloproteinase-3 levels and articular destructive changes in early and extended rheumatoid arthritis].

AIM: To estimate a relationship between matrix metalloproteinase-3 (MMP-3) levels and articular radiographic changes in early and extended rheumatoid arthritis (RA); to analyze the role of this biomarker in predicting the progression of joint destruction in RA. SUBJECTS AND METHODS: Forty-five patients with early RA and 42 with extended RA were examined. Radiography of the hands and distal feet was performed before and one year after therapy. Serum MMP-3 levels were measured by an enzyme immunoassay prior to and 12 and 24 weeks after treatment. RESULTS: After 52 weeks, in the early RA group, 16 patients continued monotherapy with methotrexate (MT); because of its inefficiency, 29 additionally received a biological agent in different follow-up periods. The extended RA group took tocilizumab for 24 weeks, then the drug was discontinued and the patients continued the former therapy with disease-modifying antirheumatic drugs, nonsteroidal anti-inflammatory drugs, and glucocorticosteroids. One year later, radiographic progression was recorded in 20.5 and 22.5% of the patients with early and extended RA, respectively. ROC analysis indicated that in the early RA group the MMP-3 level of more than 34.3 ng/ml at 12 weeks of MT therapy was associated with the radiographic progression of articular destructive changes after 52 weeks of therapy (the area under the curve (AUC) was 0.7; 95% confidence interval (CI) 0.46 to 0.93). In the patients with extended RA, the baseline MMP-3 levels of ≤51.3 ng/ml was related to no radiographic progression following 52 weeks (AUC, 0.587; 95% CI 0.33 to 0.84). CONCLUSION: MMP-3 may be regarded as an early marker for joint destruction in RA. The determination of MMP-3 level with other immunological markers may be useful to identify a group of patients who have a potentially severer disease course and need more intensive therapy.

[The clinical informativeness of detection of antibodies to citrullinated proteins under rheumatoid arthritis].

The main diagnostic laboratory markers of rheumatoid arthritis are IgM rheumatoid factor and antibodies to citrullinated proteins. The IgM rheumatoid factor is a sensitive but insufficiently specific marker of rheumatoid arthritis. The antibodies to citrullinated proteins have a higher specificity for diagnostic of rheumatoid arthritis. The antibodies to cyclic citrullinated peptide and modified citrullinated vimentin are the main representatives of family of antibodies to citrullinated proteins applying in clinical diagnostic practice. The study was carried out to deternine the role of antibodies to citrullinated proteins and modified citrullinated vimentin in diagnostic, evaluation of activity and severity of destructive alterations under rheumatoid arthritis. The samplings of 993 patients with reliable diagnosis of rheumatoid arthritis. 179 patients with other rheumatoid diseases and 30 healthy donors were examined. The measurement of serum concentration of IgM rheumatoid factor and C-reactive protein was implemented by immune nephelometric analysis and antibodies to citrullinated proteins were analyzed by enzymoimmunoassay The erythrocyte sedimentation rate was established using the Westergreen technique. It was established that antibodies to modified citrullinated vimentin had the highest diagnostic specificity (83%), antibodies to cyclic citrullinated peptide had the highest diagnostic specificity (87%). The diagnostic specificity of joint detection of IgM rheumatoid factor, antibodies to citrullinated proteins and antibodies to modified citrullinated vimentin made up to 87%. In patients negative to rheumatoid factor the rate ofdetection of antibodies to citrullinated proteins made up to 34% and antibodies to modified citrullinated vimentin made up to 48%. The diagnostic effectiveness of detection of antibodies to citrullinitted proteins (ratio of likelihood of positive and negative results of test was correspondingly 5.5 and 0.3; area under ROC curve 0.8) and antibodies to modified citrullinated vimentin (ratio of likelihood of positive and negative results of test was correspondingly 4.4 and 0.2; area under ROC curve 0.9) surpassed the same in analysis of IgM rheumatoid factor (ratio of likelihood of positive results--3.2, ratio of likelihood of negative results--0.4, area under ROC curve--0.8). The weak positive correlation relationship was established between concentration of antibodies to cyclic citrillinatedpeptide/antibodies to modified citrullinated vimentin in blood serum and indicators of clinical laboratory activity of rheumatoid arthritis (ESR, CRP DAS 28, (r-0.2. p < 0.05). The high positive levels of antibodies to modified citrullinated vimentin associated with expressed destructive affection of joints (p < 0.02). The antibodies to cyclic citrullinated peptide are the most highly specific and clinically informative laboratory diagnostic marker of rheumatoid arthritis. The detection of antibodies to modified citrullinated vimentin is an important additional serological test to diagnose rheumatoid arthritis in IgM rheumatoid factor-negative and/or antibodies to cyclic citrullinated peptide-negative patients and to forecast severe destructive affection of joints under the given disease. The joint study of IgM rheumatoid factor, antibodies to cyclic citrullinated peptide and antibodies to modified citrullinated vimentin under rheumatoid arthritis has higher diagnostic sensitivity as compared with isolated antibodies to citrullinated proteins.

[The immunologic predictors of effect of anti-B-cell therapy under rheumatoid arthritis].

The article deals with results of study targeted to reveal laboratory biomarkers which can be useful in prognosis of effectiveness of rituximab therapy under rheumatoid arthritis. The sampling consisted of 34 patients with rheumatoid arthritis (31 women, average age 49 years, 42-64 years, mean duration of disease 66, 36-132 months). All patients were examined and received two infusions of rituximab intravenously with interval in 2 weeks against the background of standard therapy. The serum concentration of C-reactive protein, IgM rheumatoid factor IgG, IgM, IgA were measured using immune nephelometric method. The level of cyclic citrullinated peptide antibodies, modified citrullinated vimentin antibodies and IgA rheumatoid factor was measured using method of immune enzyme analysis. The panel of 27 cytokines was measured using multiplex technology xMAP. Before rituximab therapy indices DAS28 (6,12; 5. 52-6, 81), SDA1 (34.3; 23, 8-45, 9) and CDAI (31.3; 21, 8-38.5) corresponded to high activity of rheumatoid arthritis. Up to 24th week of therapy good response on criteria EULAR was registered in 15 patients, moderate response in 18 patients and was absent in 1 patient. The remission on DAS achieved more rarely in patients with initially negative/ low positive values of IgM rheumatoid factor, basal level of IgM less than 2.4 g/l and duration of disease more than 40 months. In the group of patients who attained remission on CDAI up to 24th week of therapy higher basal level of IL-IRA, IL-2, IL-8, IL-15, Eotaxin, GM-CSF, IFN-gamma, MIP-1alpha and TNF-alpha was registered In patients who attained remission on DAS 28 higher level of IL-1beta. IL-2, IL-6, G-CSF, IFN-gamma, MIP-1alpha and TNF-alpha was registered in comparison with patients with disease in active mode. The detection of basal level of IgM rheumatoid factor, IgM and also certain cytokines (IL-1beta, IL-IRA, IL-2, IL-8, IL-15, GM-CSF, IFN-gamma, MIP-1alpha, Eotaxin, TNF-alpha) can be useful in prognosis of effectiveness of rituximab therapy under rheumatoid arthritis.

The relationship of antibodies to modified citrullinated vimentin and markers of bone and cartilage destruction in rheumatoid arthritis.

Objective. To make individualised decisions regarding treatment is one of the most important challenges in clinical practise, and identification of sensitive and specific markers of prognosis is an important research question. The main objective of this study was to evaluate relationships between the level of autoantibodies, radiographic changes and laboratory markers of bone, and cartilage destruction. Methods. A total of 114 RA patients were examined. The serum concentration of IgM RF, antibodies to cyclic citrullinated peptide (anti-CCP), modified citrullinated vimentin (anti-MCV), matrix metalloproteinase 3 (MMP-3), and cartilage oligomeric matrix protein (COMP, ng/mL) were measured. The van der Heijde-modified Sharp Score was used to quantify the radiologic changes. Results. Among the patients who were high-positive for anti-MCV, the value of total modified Sharp score (mTSS) (96.5; 66-120) was higher as well as the joint space narrowing (82; 60.5-105.5), and a higher level of MMP-3 was recorded more frequently (56%) in comparison with negative/low-positive patients (57; 31-88, 50; 29-82, 31% resp., P < 0.05). The level of COMP was also higher among patients high-positive for anti-MCV (9.7; 8.1-13.1 and 6.8; 5.4-10.7, resp., P = 0.02). Conclusion. A high positive level of anti-MCV as contrasted with anti-CCP and IgM RF is associated with more pronounced destructive changes in the joints.

[Relationship of the clinical efficiency of tocilizumab therapy to the serum level of matrix metalloproteinase-3 in patients with rheumatoid arthritis].

AIM: To evaluate the impact of tocilizumab (TCZ) therapy on the level of matrix metalloproteinase-3 (MMP-3) 4, 24, and 48 weeks after treatment initiation in relation to the clinical efficiency of TCZ therapy by the Disease Activity Score (DAS28), the Clinical Disease Activity Index (CDAI), and the Simplified Disease Activity Index (SDAI). SUBJECTS AND METHODS: Forty-two rheumatoid arthritis (RA) patients who had received 6 intravenous infusions of TCZ 8 mg/kg at a 4-week interval during permanent therapy with disease-modifying anti-rheumatic drugs (DMARD) and glucocorticosteroids (GCS) were examined. Then TCZ was discontinued and the patients continued to receive the previous therapy with DMARD and GCS. The European League Against Rheumatism (EULAR) classification criteria, as well as SDAI and CDAI were used to evaluate the efficiency of TCZ therapy. The serum concentration of MMP-3 was measured by enzyme immunoassay using the test systems (Invitrogen, USA). RESULTS: After 24 weeks of TCZ therapy (at 48 weeks following trial initiation), DAS28 was 4.69 (3.86; 5.44); the SDAI of 17.8 (10.7; 29.5) and the CDAI of 17.1 (7.2; 26.2) corresponded to moderate disease activity. At 48 weeks, DAS28 remission (< 2.6 scores) remained in 5 (11.90%) patients; SDAI (< or = 3.3 scores) and CDAI (< or = 2.8 scores) remissions did in 3 (7.1%) and 4 (9.5%) patients, respectively. There was a significant reduction in MMP-3 concentrations at 4, 24, and 48 weeks of the therapy, which was 61, 73, and 49.40% of the baseline level. ROC analysis indicated that the normalization of MMP-3 levels in RA patients at 24 weeks of TCZ therapy (a cut-off < or =16.5 ng/ml) was associated with the maintenance of remission/low disease activity from SDAI and CDAI 24 weeks after the drug use (the area under the receiver operating curve was 0.762; 95% confidence interval: 0.548-0.976). CONCLUSION: Analysis of the results of 48-week TCZ therapy suggests its ability to reduce the levels of markers of bone and cartilage destruction in patients with RA. Serum MMP-3 determination at 24 weeks of therapy may be useful in predicting the maintenance of remission/low activity from SDAI and CDAI after discontinuation of the drug.

[Which patients with ovarian cancer shows the combination of trabectedin with pegylated liposomal doxorubicin].

Given the high rate of recurrence of ovarian cancer, the search for new therapeutic strategies are topical issue. According to various studies the effectiveness of drug treatment relapse depends on the platinum-free interval, increasing in proportion to its duration. If therapy is platinum-resistant recurrent ovarian cancer is a standard approach, the treatment of platinum-sensitive recurrent algorithm is not fully defined. Comparison of platinum and non-platinum combinations revealed the advantage of combined platinum- treatment for patients with platinum-free interval of more than 6 months without an increase in life expectancy. Non-platinum combination of trabected in with pegylated liposomal doxorubicin has shown comparable efficacy with an advantage in overall survival in patients with platinum-free interval of 6-12 months. A platinum-free interval prolongation by the use of non-platinum mode increases the efficiency of subsequent platinum-based therapy, increasing the life expectancy of patients. Currently under study molecular markers and prognostic factors allowing to define a group of patients who have the greatest benefit from the use trabectedin with pegylated liposomal doxorubicin as second-line chemotherapy.

[The comparative evaluation of the diagnostic value of methods of detection of antibodies to citrullinized proteins under rheumatoid arthritis].

The hyper production of large specter of autoantibodies, primarily rheumatoid factors and antibodies to citrullinized proteins, is a characteristic sign of rheumatoid arthritis. The detection of these antibodies plays an important role in diagnosing the disease, especially on its early stages. The study compared the diagnostic accuracy of different methods of detection of antibodies to citrullinized proteins under rheumatoid arthritis. The examined sample included 144 patients aged 33-58 years with reliable diagnosis of rheumatoid arthritis. The patients with systemic lupus erythematous, osteoarthritis, psoriatic arthritis, OVERLAP syndrome, ankylosing spondylitis and conditionally healthy donors consisted the comparative group. To detect antibodies to citrullinized proteins the methods of enzyme immunoassay, electrochemiluminescence, immunochromatography were applied. The study demonstrated that all the methods of detection of antibodies to citrullinized proteins have adequate diagnostic value to be implemented both in a routine clinical diagnostic practice and on the stage of screening of patients.

[Rituximab therapy for systemic manifestations and MALT lymphomas of the parotid gland in Sjögren's disease: preliminary data].

AIM: To evaluate the efficacy of rituximab (RT) in cryoglobulinemic vasculitis (CGV) and MALT lymphomas of the parotid gland (PG) in patients with Sjögren's disease (SD). SUBJECTS AND METHODS: RT therapy was performed in 13 patients with SD and CGV and in 17 with SD and PC MALT lymphoma. Eleven patients with SD received RT monotherapy and 19 with this disease had combined therapy with RT and cyclophosphan (CP). RT was used intravenously dropwise at a dose of 500 mg weekly or once every two weeks in combination with intravenous dropwise CP 1000 mg the next day with 4-6 per course. For the diagnosis of MALT lymphomas, all the patients with SD underwent incisional PG biopsy under local anesthesia at the Research Institute of Rheumatology, Russian Academy of Medical Sciences. PG biopsy specimens were histologically and immunohistochemically studied at the Russian Cancer Research Center, Russian Academy of Medical Sciences. In 11 cases, B-cell clonality was identified from immunoglobulin (Ig) heavy chain genes rearrangements, by using polymerase chain reaction at the Hematology Research Center, Ministry of Health and Social Development of the Russian Federation. RESULTS: Cutaneous manifestations of vasculitis disappeared in 75% of cases after monotherapy with RT and in 100% of cases after combination therapy with RT and CP. At 6-month follow-up, a complete response to therapy remained in 25% of the patients after a course of monotherapy and in 83% after combined therapy. Serum monoclonal Ig cryoglobulins and their urinary light chains ceased to be detectable in 75% of the patients in both groups at 3 months. At 6 months, a recurrence of mixed monoclonal cryoglobulinemia was seen in 50 and 43% of cases after monotherapy and combined therapy, respectively. The clinical and laboratory response of cryoglobunemic glomerulonephritis to combined therapy with RT and CP was complete in 60% of cases at 6-month follow-up. After RT monotherapy, the patients with SD and PG MALT lymphoma achieved a complete clinical response in 88%, of whom histological and immunohistochemical reexaminations of PG biopsy specimens revealed no signs of MALT lymphoma in 71% of cases. B-cell clonality remained in the PG biopsy specimens following RT monotherapy. After the combination of RT and CP, a complete clinical response to therapy was observed in 100% of the patients, a complete histological response and a complete molecular one were seen in 83 and 60%, respectively. CONCLUSION: RT showed its efficacy in treating SD patients with CGV and PG MALT lymphomas.