Identification of autoimmune markers in pulmonary tuberculosis

IntroductionPathogenesis of many autoimmune diseases is mainly promoted by poorly regulated and/or wrong targeted immune response to pathogens including M. tuberculosis. Autoimmunity is one of the processes with are characteristics of tuberculosis (Tbc). The aim was to determine the autoimmune clinical and immunological features in patients with pulmonary Tbc.Materials and methodsA prospective comparative study was performed in 2017 – 2019 with the inclusion of 46 patients with Tbc. The trigger factors and clinical manifestations, autoantibodies, peripheral blood B cell subsets were stained with fluorochrome-conjugated monoclonal antibodies. 40 healthy volunteers in the control group, were matched for age with no chronic diseases, contacts with TB patients and changes in their laboratory parameters. A statistical analysis was done with GraphPad Prism 6, Statistica 10 (Statsoft) and MedCalc – version 18.2.1 values.ResultsThere were no significant ASIA triggers in Tbc patients and control group. 21.1% of Tbc patients had a high level of a rheumatoid factor and in 47.4% complement system factor C3 was high; anti-MCV was detected in 60.7% of Tbc patients. Relative and absolute frequencies of “naïve” Bm1 cells and eBm5 were significantly decreased and activated pre-germinal-center Bm2’ cells were significantly increased in Tbc patients. The CD24++CD38++ B cells were increased in Tbc vs control group (10.25% vs 5.42%), p < 0.001, and 19 cell/1μL (10; 290 vs 11 cell/1μL (6; 20), p = 0.029, respectively). The frequency of CXCR3+CCR4– Tfh1 cells was significantly lower in Tbc vs control one (26.52% vs. 31.00%, p = 0.004), while CXCR3–CCR4+ Tfh2 cells were increased in Tbc (20.31% vs. controls (16.56%, p = 0.030). The absolute numbers of Tfh1 cells were decreased in the Tbc vs. control (24 cell/1μL vs. 37 cell/1μL p = 0.005).ConclusionThe results of our study showed that the detection of a rheumatoid factor, the components of complement system and anti-MCV in complex with alterations in B cells and follicular Th cell subsets may indicate a presence of autoimmunity in the pathogenesis of tuberculosis, but they are not specific. The indicators of autoimmune-related provide new opportunities in the Tbc treatment

Molecular and Cellular Mechanisms of M. tuberculosis and SARS-CoV-2 Infections-Unexpected Similarities of Pathogenesis and What to Expect from Co-Infection

Tuberculosis is still an important medical and social problem. In recent years, great strides have been made in the fight against M. tuberculosis, especially in the Russian Federation. However, the emergence of a new coronavirus infection (COVID-19) has led to the long-term isolation of the population on the one hand and to the relevance of using personal protective equipment on the other. Our knowledge regarding SARS-CoV-2-induced inflammation and tissue destruction is rapidly expanding, while our understanding of the pathology of human pulmonary tuberculosis gained through more the 100 years of research is still limited. This paper reviews the main molecular and cellular differences and similarities caused by M. tuberculosis and SARS-CoV-2 infections, as well as their critical immunological and pathomorphological features. Immune suppression caused by the SARS-CoV-2 virus may result in certain difficulties in the diagnosis and treatment of tuberculosis. Furthermore, long-term lymphopenia, hyperinflammation, lung tissue injury and imbalance in CD4+ T cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression

Immunogenetic Predictors of Severe COVID-19

According to an analysis of published data, only 20% of patients with the new coronavirus infection develop severe life-threatening complications. Currently, there are no known biomarkers, the determination of which before the onset of the disease would allow assessing the likelihood of its severe course. The purpose of this literature review was to analyze possible genetic factors characterizing the immune response to the new coronavirus infection that could be associated with the expression of angiotension-converting enzyme 2 (ACE-2) and related proteins as predictors of severe Corona virus disease 2019 (COVID-19). We analyzed original articles published in Medline, PubMed and Scopus databases from December 2019 to November 2020. For searching articles, we used the following keywords: New coronavirus infection, Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), COVID-19, severe course, complications, thrombosis, cytokine storm, ACE-2, biomarkers. In total, 3714 publications were selected using the keywords, of which 8 were in congruence with all the criteria. The literature analysis of the association of immunogenic characteristics and the expression of ACE-2 and related proteins with the development of severe COVID-19 revealed following genetic factors: HLA-B*46:01 genotype, CXCR6 gene hypoexpression, CCR9 gene expression, TLR7, rs150892504 mutations in the ERAP2 gene, overexpression of wild-type ACE-2, TMPRSS2 and its different polymorphisms. Genes, associated with the severe course, are more common among men. According to the analysis data, it can be assumed that there are population differences. However, the diagnostic significance of the markers described must be confirmed with additional clinical studies

Sarcoidosis and Autoimmune Inflammatory Syndrome Induced by Adjuvants

Currently, sarcoidosis remains one of the diseases with unknown etiology, which significantly complicates its diagnosis and treatment. Various causes of sarcoidosis have been studied for many years. Both organic and inorganic trigger factors, provoking the development of granulomatous inflammation are considered. However, the most promising and evidence-based hypothesis is the development of sarcoidosis as an autoimmune disease, provoked by various adjuvants in genetic predisposed individuals. This concept fits into the structure of the autoimmune/inflammatory syndrome, induced by adjuvants (ASIA) that was proposed in 2011 by Professor Shoenfeld Y. In this paper, the authors reveal the presence of major and minor ASIA criteria for sarcoidosis, propose a new concept of the course of sarcoidosis within the framework of ASIA, and point out the difficulties in creating a model of the disease and the selection of therapy. It is obvious that the data obtained not only bring us closer to understanding the nature of sarcoidosis, but also potentiate new studies confirming this hypothesis by obtaining a model of the disease

The effect of human leukocyte Antigens-DRB1 alleles on development of different tuberculosis forms in children

Background: Nowadays, there is no doubt that the development of infectious process is determined not only by individual features of a human, but also by features of infection agent. It is commonly known that ability to form an adequate immune response is based on immunogenetic peculiarities of macroorganism. Methods: The immunogenetic study was performed in 228 children from 1 to 15 years old with different manifestations of tuberculosis (TB). Control group was consisted of 446 adult healthy donors-residents of the Northwestern region of Russia. Human leukocyte antigens (HLA)-DRB1* allelic genes were assessed in all individuals. Results: HLA-DRB1 alleles *01, *03, *11, *13, *07, and *15 were observed significantly rare in children with TB in comparison with healthy donors that may indicate their protective role in the development of the disease. It was also noticed that DRB1 *07 and *15 alleles were observed significantly rare in children with lung TB in comparison with other forms of disease that allows to assume a protective function of these alleles for lung TB with no influence on development of generalized TB. This assumption requires further researches. Conclusion: As a result of the study, statistically significant differences in the distribution of HLA-DRB1* alleles in children with TB in comparison with a control group for *01, *03, *11, *13, *07, *15, and *16 alleles were found. It may indicate their protective role in the development of TB. DRB1 *07 and *15 alleles were observed significantly rare in children with single TB than in children with generalized TB and healthy controls

Efficacy of Different Types of Therapy for COVID-19: A Comprehensive Review

A new coronavirus disease (COVID-19) has already affected millions of people in 213 countries. The possibilities of treatment have been reviewed in recent publications but there are many controversial results and conclusions. An analysis of the studies did not reveal a difference in mortality level between people treated with standard therapy, such as antiviral drugs and dexamethasone, and new antiviral drugs/additional immune therapy. However, most studies describe clinical improvement and a decrease in mortality among patients with severe and critical conditions, with the early initiation of additional immune therapy. Possible new targets based on viral life cycles were considered. Unfortunately, the data analysis on the efficacy of different medicine and therapy regimens among patients with COVID-19, showed little success in decreasing the mortality rate in all treatment methods. Some efficacy has been shown with an immunosuppressive therapy in small patient samples, but when a larger number of patients were analyzed the data did not differ significantly from the control groups

Detection of Anti-Vimentin Antibodies in Patients with Sarcoidosis

There is a need to further characterize the antibody response to vimentin in relation to its possible involvement in pathogenicity of sarcoidosis and other lung disorders. Objectives: We investigated serum samples from patients with sarcoidosis, healthy controls and controls with other non-infectious lung diseases., to evaluate levels and frequency of these antibodies. Materials and methods: A retrospective-prospective comparative study was performed in the years 2015–2019. Sera from 93 patients with sarcoidosis, 55 patients with non-infectious lung diseases and 40 healthy subjects was examined for presence of autoantibodies to mutated citrullinated vimentin (anti-MCV). Patients with elevated anti-MCV levels were tested for antibodies to a cyclic citrullinated peptide (anti-CCP) and citrullinated vimentin (anti-Sa). In all cases ELISA assays was used. The results were considered statistically significant at p-value less than 0.05. Results of the study: The high concentrations of anti-MCV antibodies were more frequent in patients with sarcoidosis (40.9% of the cases, 38/93), compared to the control groups (23.6% and 25.0% of cases, respectively). In sarcoidosis, clinical symptoms similar to the autoimmune pathology were described. A moderate positive correlation between the anti-MCV and anti-Sa antibodies (r = 0.66) was found in 13 patients with sarcoidosis. There was no significant difference between the levels of the anti-MCV and the anti-CCP in patients with non-infectious lung diseases and the healthy control group. Conclusion: Antibodies to citrullinated cyclic peptides are not significant in the pathogenesis of sarcoidosis and other investigated pulmonary diseases (COPD, granulomatosis with polyangiitis, alveolitis) and based on their low concentration, it can be assumed that citrullination and modification of vimentin is not a key factor in the development of an autoimmune response in patients with sarcoidosis

Post COVID-19 Syndrome in Patients with Asymptomatic/Mild Form

Post COVID-19 Syndrome (PCS) is a complex of various symptoms developing a month or more after the acute phase of the disease. The cases of PCS development among patients with asymptomatic/mild forms are frequently reported; however, the pathogenesis of PCS in this group of patients is still not completely clear. The publications about COVID-19 which were published in online databases from December 2019 to September 2021 are analyzed in this review. According to the analysis, PCS develops on average in 30–60% of patients, mainly among women. Fatigue, shortness of breath, cough, and anosmia were reported as the most common symptoms. The possible association between the described PCS symptoms and brain damage was revealed. We assume the possibility of an alternative course of COVID-19, which develops in genetically predisposed individuals with a stronger immune response, in which it predominantly affects the cells of the nervous system, possibly with the presence of an autoimmune component, which might have similarity with chronic fatigue syndrome or autoimmune disautonomia. Thus, the gender (female) and the presence of anosmia during an asymptomatic or mild course of the disease can be predictive factors for the development of PCS, which can be caused by autoimmune damage to neurons, glia, and cerebral vessels

A comparison of intradermal test with recombinant tuberculosis allergen (diaskintest) with other immunologic tests in the diagnosis of tuberculosis infection

Background: The WHO strategy for eradication of tuberculosis (TB) by 2035 (The End TB Strategy) is aimed at an early and precise diagnosis and subsequent effective treatment of TB patients. Currently, there is no gold standard for the diagnosis of latent TB infection. This study evaluated the diagnostic capabilities of a new intradermal test using recombinant TB allergen (Diaskintest) compared with tuberculin skin test (TST) and commercial TB interferon-gamma release assays (IGRAs). Methods: A post-hoc data analysis that involved examining 860 HIV-negative, bacillus Calmette–Guérin (BCG)-vaccinated persons aged 1–65 years who visited the TB health-care institutions of Saint Petersburg to rule out or confirm an active TB was conducted from 2011 to 2016. Results: A high degree of consistency of the Diaskintest results with the enzyme-linked immunospot and QuantiFERON-TB Gold In-Tube test (ELISPOT and QFT) results was observed in the examined pediatric population (n = 696), with a Diaskintest cutoff ≥5 mm: the kappa consistency indices were 1.000 and 0.937, for ELISPOT and QFT, respectively. A high sensitivity of Diaskintest, comparable with the IGRA tests, was observed in patients with a confirmed TB diagnosis in all age groups. The sensitivity of Diaskintest in patients of the TB/MTB + group aged 18 years and older was 88.7%; of ELISPOT, 90.6%; of QFT, 87.0%. The conducted analysis has shown a high concordance of results of the commercial TB tests in adult HIV-negative patients (n = 164) with a Diaskintest cutoff ≥5 mm: the kappa indices were 0.805 and 0.636 (Diaskintest vs. ELISPOT and QFT, respectively) among BCG-vaccinated people. Conclusion: According to the WHO recommendations, replacing the TST by IGRAs is not recommended as a public health intervention in resource-constrained settings because the IGRA tests are more costly and technically complex to conduct than the TST. Diaskintest has comparable complexity to the TST and its performance is close to that of IGRA in a BCG-vaccinated population. Thus, our study demonstrates that replacing the TST by Diaskintest can be recommended as a public health intervention in resource-constrained and universal BCG vaccination settings

Small Fiber Neuropathy in Sarcoidosis

Sarcoidosis (SC) is a granulomatous disease of an unknown origin. The most common SC-related neurological complication is a small fiber neuropathy (SFN) that is often considered to be the result of chronic inflammation and remains significantly understudied. This study aimed to identify the clinical and histological correlates of small fiber neuropathy in sarcoidosis patients. The study was performed in 2018–2019 yy and included 50 patients with pulmonary sarcoidosis (n = 25) and healthy subjects (n = 25). For the clinical verification of the SFN, the “Small Fiber Neuropathy Screening List” (SFN-SL) was used. A punch biopsy of the skin was performed followed by enzyme immunoassay analysis with PGP 9.5 antibodies. Up to 60% of the sarcoidosis patients reported the presence of at least one complaint, and it was possible that these complaints were associated with SFN. The most frequent complaints included dysfunctions of the cardiovascular and musculoskeletal systems and the gastrointestinal tract. A negative, statistically significant correlation between the intraepidermal nerve fiber density (IEND) and SFN-SL score was revealed. In patients with pulmonary sarcoidosis, small fiber neuropathy might develop as a result of systemic immune-mediated inflammation. The most common symptoms of this complication were dysautonomia and mild sensory dysfunction