Impaired B-cell immunological tolerance plays a central role in the pathogenesis of immuno-inflammatory rheumatic diseases (IIRD). B-cells link innate and acquired immunity: they express Toll-like receptors that respond to danger signals; act as antigen-presenting cells; induce an antigen-specific immune response; determine the development of immunological memory; and synthesize a wide range of cytokines that regulate (stimulate or suppress) an immune response and inflammation. In IIRD, there are metabolic and B-cellular signaling disturbances that lead to defects in B-regulatory, T-regulatory, follicular T-helper, and dendritic cells. B-cells synthesize organ-nonspecific and organspecific autoantibodies that are biomarkers  for autoimmune diseases and play an important role in their immunopathogenesis. Anti-B-cell therapy that causes B-cell depletion in blood and target organs is effective in a wide range of IIRD. Its efficiency is determined by various mechanisms, such as suppression of pathogenic autoantibody synthesis; modulation of the function of B-cells (antigen presentation, cytokine synthesis, and costimulation), T-lymphocytes and dendritic cells. Further study of a strategy for targeted anti-B-cell therapy, mechanisms of action, and new targets is important for the progress of modern rheumatology to improve the treatment strategy of IIRD.

Раннее выявление идиопатического легочного фиброза: дифференциальная диагностика с интерстициальными поражениями легких при системных иммуновоспалительных ревматических заболеваниях

Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by hyperproduction of non-organ-specific autoantibodies to various components of the cell nucleus and the development of immune-inflammatory damage to internal organs. Currently, SLE is considered as a prototype of a systemic human autoimmune pathology, the central mechanism of immunopathogenesis of which is a violation of immunological tolerance to self-antigens, due to a complex interaction of genetic, epigenetic, environmental factors. The publication discusses the history of the study of SLE, the contribution of Russian scientists (V.A. Nasonova and others) to the study of th is problem, current trends in clinical and scientific research related to the improvement of diagnostic criteria and pharmacotherapy of this disease. 

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Systemic lupus erythematosus: history and modernity


               Summary
               
                  COVID-19 had a mild clinical course in patients with Agammaglobulinemia lacking B lymphocytes, whereas it developed aggressively in Common Variable Immune Deficiency. Our data offer mechanisms for possible therapeutic targets.
               
            

Iconographies supplémentaires de l'article : A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia

Rheumatoid arthritis (RA) is an immune-mediated rheumatic disease (IMRDs) characterized by chronic erosive arthritis and systemic damage to internal organs, leading to early disability and reduced life expectancy in patients. A particularly important place among the systemic manifestations of RA is occupied by interstitial lung diseases (ILD) – the most severe form of pulmonary pathology in RA, defined as RA-ILD, which is pathogenetically associated with risk factors (smoking, etc.) and autoimmune mechanisms underlying RA. RA-ILD is a subtype of RA characterized by a severe course and a poor prognosis и неблагоприятным прогнозом. The review presents new data regarding risk factors and biomarkers for RA-ILD; modern diagnostic capabilities based on the use of functional lung tests, high-resolution computed tomography, ultrasound examination of the lungs. Particular attention is paid to the efficacy and safety of pharmacotherapy, including methotrexate, biologics, JAK inhibitors, and antifibrotic therapy. An algorithm for the pharmacotherapy of RA-ILD has been proposed.

Interstitial lung disease in rheumatoid arthritis: A multidisciplinary problem in rheumatology and pulmonology

BACKGROUND
Currently, observations are accumulating indicating the negative effect of therapy with a number of biologic disease-modifying anti-rheumatic drugs (bDMARDs) drugs on the course of COVID-19. These facts determine the relevance of studying the factors of severe course and unfavorable outcome in immuno-inflammatory rheumatic diseases (IIRD) patients treated with bDMARDs in order to develop tactics for managing this category of patients in a pandemic.


AIM
To evaluate the influence of clinical and demographic factors on the risk of development, severity of the course and clinical outcomes of a new coronavirus infection in patients suffering from IIRD and receiving therapy with genetically engineered biological drugs.


MATERIALS AND METHODS
A retrospective analysis of the database of the register of patients with IIRD receiving bDMARDs in the Novosibirsk region was performed, which included 318 patients, 94 of whom had indications of having suffered viral infection/pneumonia for the period from 01.04.2020 to 31.12.2020.


RESULTS
According to the data obtained, at the time of the analysis, 94 people out of 318 patients with IIRD had a new coronavirus infection. Most (53%) of the patients had a mild infection. At the same time, the nosological form, the use of anti-rheumatic drugs and glucocorticoids did not increase the risks of severe coronavirus infection. When using bDMARDs, only anti-B-cell therapy (rituximab) associated with statistically significant increase in the risk of severe/extremely severe COVID-19. The mortality rate according to the analysis of the register was 6,38%.


CONCLUSION
Patients with IIRD have a high risk of severe coronavirus infection, while the severity of the disease is associated with the type of therapy performed.

[Immuno-inflammatory rheumatic diseases and COVID-19: analysis of clinical outcomes according to the data of the register of patients of the Novosibirsk region receiving therapy with genetically engineered biological drugs].

In patients with immune-mеdiated (autoimmune) rheumatic diseases (IMIRD), there are a number of factors (advanced age, uncontrolled inflammation, initially irreversible damage to internal organs, comorbid pathology, genetic and other factors) that can potentially lead to an increase in “sensitivity” to SARS-CoV -2 (severe acute respiratory syndrome coronavirus-2) and concomitant viral and bacterial infections, an increase in the risk of a severe course of COVID-19 (coronavirus disease 2019), a decrease in the effectiveness of therapy for both IMIRDs and COVID-19. An important area of pharmacotherapy for IMIRDs and other autoimmune diseases is associated with the use of anti-B-cell drugs, primarily rituximab (RTX), which is a chimeric (mouse/human) monoclonal antibody (mAb) to the CD20 antigen of B cells. At present, in Russia, the RTM biosimilar, acellbia (BIOCAD), is widely used, which is not inferior to RTX in terms of efficiency and safety. The problems of anti-B-cell therapy during the COVID-19 pandemic in relation to the risk of infection, severe course and insufficient effectiveness of vaccination against SARSCoV- 2 are considered. According to the recommendations of the Association of Rheumatologists of Russia, a more rigorous assessment of indications for induction and maintenance therapy of RTX therapy and harmonization of the timing of drug administration and vaccination is required.

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Е. Л. Насонов

Papers

Деплеция в-клеток при иммуновоспалительных ревматических заболеваниях и коронавирусная болезнь 2019 (covid-19)