Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.

Background. Mitoxantrone (MTX) and Rituximab (RTX) are successfully used for treatment of multiple sclerosis (MS) and can be combined to increase efficacy. Objective. We used MTX, RTX, and methylprednisolone in a single combined regiment and observed patients prospectively. Methods. We present results of observational pilot study of combined therapy of RTX and MTX in 28 patients with active MS. Therapeutic protocol consisted of two infusions within 14 days. First infusion was 1000 mg methylprednisolone (MP) IV, 1000 mg RTX IV, and 20 mg MTX IV. On day 14, 1000 mg MP IV and 1000 mg RTX IV were given. Patients were followed prospectively from 12 to 48 months. Results and Conclusion. There were no relapses among all 28 patients during the observation period. B-cell depletion of CD19+ and CD19+/CD27+ memory B-cell subpopulation in both compartments was confirmed in all patients at 6 months. We found a more rapid reconstitution of B cells in the CSF than in the peripheral blood and longstanding depression of CD19+CD27+ memory B-cell. Conclusion. Effectiveness of combined regimen of RTX and MTX could be related to longstanding depletion of CD19+CD27+ memory B-cell subset

Антитела к различным посттрансляционным модификациям виментина у больных ревматоидным артритом

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease (ARD) associated with the production of broad-spectrum antibodies, the detection of which is of important diagnostic and prognostic values. The problems of RA diagnosis are associated with the limited sensitivity of currently used serological markers.Objective: to evaluate the diagnostic informative value of autoantibodies against different post-translationally modified (PTM) vimentin peptides in patients with RA and other ARDs.Patients and methods. The frequency of autoantibodies against different isoforms of vimentin was estimated in 144 patients with RA, in 36 patients with other ARDs (ankylosing spondylitis and scleroderma systematica), and in 25 patients of a control group, who had no rheumatic diseases. Antibodies against different PTM vimentin peptides obtained using citrullination, carbamylation/homocitrullination, and acetylation were determined. Anti-citrullinated vimentin (anti-CitVim) peptide, anti-carbamylated vimentin (anti-CarVim) peptide, and anti-acetylated vimentin (anti-AcVim) peptide autoantibodies of IgG and IgA classes were estimated in the serum by enzyme immunoassay.Results. The results of the study showed that IgG and IgA anti-CitVim had the maximum area under the ROC curve (AUC) (0.859 and 0.855, respectively). A slightly smaller AUC was seen in IgG anti-CarVim (0.85), IgG anti-AcVim (0.784), and IgA anti-AcVim (0.651). The diagnostic sensitivity and diagnostic specificity were 66.2 and 96.77% for IgG anti-CitVim, 60.56 and 91.94% for IgA anti-CitVim, 91.55 and 53.23% for IgG anti-CarVim, 63.38 and 93.55% for IgG anti-AcVim, and 49.3 and 70.97%, IgA anti-AcVim, respectively. Positivity for IgG anti-CitVim, IgG anti-CarVim, and IgG anti-AcVim, and anti-IgA CitVim was significantly more frequently detected in patients with RA than in those with other ARDs and in the control group (p<0.05). Thus, the identified autoantibodies against modified vimentin peptides proved to be diagnostically useful serological markers in RA. IgA anti-CarVim and IgA anti-AcVim can also be used in the diagnosis of RA in patients who are seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Conclusion. When the upper reference limits are set for IgG anti-CitVim (20 U/ml), IgA anti-CitVim (8.95 U/ml), IgG anti-CarVim (6.25 U/ml), IgG anti-AcVim (17.1 U/ml), and IgA anti-AcVim (9.85 U/ml), antibodies against different isoforms of vimentin are recommended for use as additional laboratory tests to diagnose RA.Ревматоидный артрит (РА) – наиболее распространенное аутоиммунное ревматическое заболевание (АРЗ), ассоциированное с продукцией широкого спектра антител, определение которых имеет важное диагностическое и прогностическое значение. Проблемы диагностики РА связаны с ограниченной чувствительностью применяемых в настоящее время серологических маркеров.Цель исследования – оценка диагностической информативности аутоантител к различным посттрансляционным модификациям (ПТМ) виментина у пациентов с РА и другими АРЗ.Пациенты и методы. Оценивали встречаемость аутоантител к различным изоформам виментина у 144 пациентов с РА, 36 больных с другими АРЗ (анкилозирующий спондилоартрит и системная склеродермия), а также у 25 пациентов контрольной группы, не страдавших ревматическими заболеваниями. Определяли антитела к различным ПТМ виментина, полученным методами цитруллинирования, карбамилирования/гомоцитруллинирования и ацетилирования. Аутоантитела к цитруллинированному (аnti-citrullinated vimentin peptide, анти-CitVim), карбамилированному (anti-carbamylated vimentin peptide, анти-CarVim) и ацетилированному (аnti-acetylated vimentin peptide, анти-AcVim) виментину классов IgG и IgA оценивали в сыворотке крови с помощью иммуноферментного анализа.Результаты. Как показали результаты исследования, максимальной площадь под характеристической кривой (AUC) оказалась у анти-CitVim IgG и IgA – 0,859 и 0,855 соответственно. Немного меньшая AUC была у анти-CarVim IgG (0,85), анти-AcVim IgG (0,784) и анти-AcVim IgA (0,651). Диагностическая чувствительность и диагностическая специфичность для анти-CitVim IgG составили 66,2 и 96,77%, анти-CitVim IgА – 60,56 и 91,94%, анти-CarVim IgG – 91,55 и 53,23%, анти-AcVim IgG – 63,38 и 93,55% и анти-AcVim IgА – 49,3 и 70,97% соответственно. Позитивность по анти-CitVim, анти-CarVim и анти-AcVim класса IgG, а также анти-CitVim IgA значительно чаще выявлялась у больных РА, чем у пациентов с другими АРЗ и в контрольной группе (p<0,05). Таким образом, выявленные аутоантитела к модифицированным пептидам виментина оказались диагностически полезными серологическими маркерами при РА. Анти-CarVim и анти-AcVim класса IgA могут быть также использованы в диагностике РА у пациентов, серонегативных по ревматоидному фактору и антителам к циклическому цитруллиновому пептиду.Выводы. При установленных значениях верхней границы нормы для анти-CitVim IgG – 20 ед/мл, анти-CitVim IgА – 8,95 ед/мл, анти-CarVim IgG – 6,25 ед/мл, анти-AcVim IgG – 17,1 ед/мл, анти-AcVim класса IgА – 9,85 ед/мл аутоантитела к различным изоформам виментина рекомендуются к применению в качестве дополнительных лабораторных тестов для диагностики РА

Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis

Background Secukinumab is an anti–interleukin-17A monoclonal antibody that has been shown to control the symptoms of ankylosing spondylitis in a phase 2 trial. We conducted two phase 3 trials of secukinumab in patients with active ankylosing spondylitis. Methods In two double-blind trials, we randomly assigned patients to receive secukinumab or placebo. In MEASURE 1, a total of 371 patients received intravenous secukinumab (10 mg per kilogram of body weight) or matched placebo at weeks 0, 2, and 4, followed by subcutaneous secukinumab (150 mg or 75 mg) or matched placebo every 4 weeks starting at week 8. In MEASURE 2, a total of 219 patients received subcutaneous secukinumab (150 mg or 75 mg) or matched placebo at baseline; at weeks 1, 2, and 3; and every 4 weeks starting at week 4. At week 16, patients in the placebo group were randomly reassigned to subcutaneous secukinumab at a dose of 150 mg or 75 mg. The primary end point was the proportion of patients with at least 20% improvement in Assessment of Spondyloarthritis International Society (ASAS20) response criteria at week 16. Results In MEASURE 1, the ASAS20 response rates at week 16 were 61%, 60%, and 29% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for both comparisons with placebo); in MEASURE 2, the rates were 61%, 41%, and 28% for subcutaneous secukinumab at doses of 150 mg and 75 mg and for placebo, respectively (P<0.001 for the 150-mg dose and P=0.10 for the 75-mg dose). The significant improvements were sustained through 52 weeks. Infections, including candidiasis, were more common with secukinumab than with placebo during the placebo-controlled period of MEASURE 1. During the entire treatment period, pooled exposure-adjusted incidence rates of grade 3 or 4 neutropenia, candida infections, and Crohn’s disease were 0.7, 0.9, and 0.7 cases per 100 patient-years, respectively, in secukinumab-treated patients. Conclusions Secukinumab at a subcutaneous dose of 150 mg, with either subcutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16. Secukinumab at a subcutaneous dose of 75 mg resulted in significant improvement only with a higher intravenous loading dose. (Funded by Novartis Pharma; ClinicalTrials.gov numbers, NCT01358175 and NCT01649375.

Idiopathic recurrent pericarditis — a paradigm shift?

Idiopathic recurrent  pericarditis (IRP) is a relatively rare inflammatory disease of the pericardium,  often  requiring  emergency medical  care,   associated with a  high percentage of temporary  disability and  significant  economic  costs.  The review presents various  points  of view on  the  pathogenesis of recurrent   pericarditis, discusses the role of autoinflammation.  It touches on treatment issues  based  on modern  data  on the IRP immunopathogenesis, and considers promising areas  of laboratory diagnostics

Antibodies against post-translationally modified vimentin peptides in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease (ARD) associated with the production of broad-spectrum antibodies, the detection of which is of important diagnostic and prognostic values. The problems of RA diagnosis are associated with the limited sensitivity of currently used serological markers.Objective: to evaluate the diagnostic informative value of autoantibodies against different post-translationally modified (PTM) vimentin peptides in patients with RA and other ARDs.Patients and methods. The frequency of autoantibodies against different isoforms of vimentin was estimated in 144 patients with RA, in 36 patients with other ARDs (ankylosing spondylitis and scleroderma systematica), and in 25 patients of a control group, who had no rheumatic diseases. Antibodies against different PTM vimentin peptides obtained using citrullination, carbamylation/homocitrullination, and acetylation were determined. Anti-citrullinated vimentin (anti-CitVim) peptide, anti-carbamylated vimentin (anti-CarVim) peptide, and anti-acetylated vimentin (anti-AcVim) peptide autoantibodies of IgG and IgA classes were estimated in the serum by enzyme immunoassay.Results. The results of the study showed that IgG and IgA anti-CitVim had the maximum area under the ROC curve (AUC) (0.859 and 0.855, respectively). A slightly smaller AUC was seen in IgG anti-CarVim (0.85), IgG anti-AcVim (0.784), and IgA anti-AcVim (0.651). The diagnostic sensitivity and diagnostic specificity were 66.2 and 96.77% for IgG anti-CitVim, 60.56 and 91.94% for IgA anti-CitVim, 91.55 and 53.23% for IgG anti-CarVim, 63.38 and 93.55% for IgG anti-AcVim, and 49.3 and 70.97%, IgA anti-AcVim, respectively. Positivity for IgG anti-CitVim, IgG anti-CarVim, and IgG anti-AcVim, and anti-IgA CitVim was significantly more frequently detected in patients with RA than in those with other ARDs and in the control group (p&lt;0.05). Thus, the identified autoantibodies against modified vimentin peptides proved to be diagnostically useful serological markers in RA. IgA anti-CarVim and IgA anti-AcVim can also be used in the diagnosis of RA in patients who are seronegative for rheumatoid factor and anti-cyclic citrullinated peptide antibodies.Conclusion. When the upper reference limits are set for IgG anti-CitVim (20 U/ml), IgA anti-CitVim (8.95 U/ml), IgG anti-CarVim (6.25 U/ml), IgG anti-AcVim (17.1 U/ml), and IgA anti-AcVim (9.85 U/ml), antibodies against different isoforms of vimentin are recommended for use as additional laboratory tests to diagnose RA

The possibility of early detection of atherosclerotic vascular lesions in rheumatic diseases

Identification of subclinical lesions of the heart and blood vessels in patients with rheumatic diseases (RD), as well as the comparison of subclinical markers of cardiovascular lesions in patients with RD and RD patients without having one of the risk factors for cardiovascular disease. Surveyed 56 patients (15 men and 41 female) at the age of 45.2 ± 13.42 years with different rheumatic diseases. For the comparison group surveyed residents of one of the districts of Saint Petersburg (50 people). All patients have been conducted questioning, characterizes lifestyle, risk factors, comorbidity and drug therapy. Anthropometry were measured in weight, height with a calculation of body mass index, waist circumference, hip circumference. Endothelial dysfunction study conducted on the Endo Pat 2000 (company “Itamar Medical Ltd, Israel): reactive hyperemia index (RHI) and augmentation index (AI). Dysfunction of the endothelium have registered a value of RHI 9.6 m/s compared to the 2nd and 3rd groups of patients with RD. We have identified correlate titer of antinuclear factor, reactive hyperemia index (RHI), augmentation index (AI, EndoPat), the central pulse pressure (PP) show integration structures of the cardiovascular system in the pathological process in RD, including asymptomatic from the system

ANGIOGENIC AND ANGIOSTATIC CHEMOKINES LEVEL IN NORMAL SYNOVIAL FLUID

Chemokines are believed to play an important role in immunopathogenesis of different joint diseases. One of important problems in studies of synovial fluid is determination of normal level of chemokines from control patients. In our study we determined concentrations of number of chemokines in relatively normal synovial fluid from subjects with background traumatic joint injury without systemic or local inflammation at the moment of study. Results for several CC- and CXC-chemokines are shown for the first time. Therefore, our data can be further used in analysis of synovial fluid chemokine profile in studies of joint disease of different etiology