Immunoinflammatory Diseases Research Articles

Resilience to Global Health Challenges Through Nutritional Gut Microbiome Modulation

As the world faces an escalating challenge of non-communicable diseases (NCDs), with phenotypes ranging from allergic chronic immuno-inflammatory diseases to neuropsychiatric disorders, it becomes evident that their seeds are sown during the early stages of life. Furthermore, within only a few decades, human obesity has reached epidemic proportions and now represents the most serious public health challenge of our time. Recent demonstrations that a growing number of these conditions are linked to aberrant gut microbiota composition and function have evoked active scientific interest in host-microbe crosstalk, characterizing and modulating the gut microbiota in at-risk circumstances. These efforts appear particularly justified during the most critical period of developmental plasticity when the child’s immune, metabolic, and microbiological constitutions lend themselves to long-term adjustment. Pregnancy and early infancy epitomize an ideal developmental juncture for preventive measures aiming to reduce the risk of NCDs; by promoting the health of pregnant and lactating women today, the health of the next generation(s) may be successfully improved. The perfect tools for this initiative derive from the earliest and most massive source of environmental exposures, namely the microbiome and nutrition, due to their fundamental interactions in the function of the host immune and metabolic maturation.

Forging the Future: B Cell Activating Factor's Impact on Nephrotic Syndrome.

Nephrotic syndrome is the most common glomerular disease in children. While the exact pathogenesis of nephrotic syndrome is not fully understood, recent research has shed light on some of the underlying mechanisms involved in it. Improvement by B cell depletion therapy using antiCD20 in nephrotic syndrome has led to a paradigm shift from immunoinflammatory disease influenced by T cell dysregulation to B cell involvement in the pathogenesis of nephrotic syndrome. The expression of the B cell activating factor (BAFF), an essential cytokine for the maturation and differentiation of B lymphocytes, in the podocytes of paediatric patients with nephrotic syndrome is known to be associated with worse renal outcomes. The pro-inflammatory cytokines and pathogenic antibodies produced by B cells allegedly cause podocyte injury leading to proteinuria due to effacement of foot processes. Considering the role of the BAFF in B cell proliferation and antibody production, BAFF signalling is a potential target for development as targeted therapy in nephrotic syndrome. Nevertheless, there is limited research regarding the role of BAFF in nephrotic syndrome, and the exact mechanism of BAFF involvement in the pathogenesis of nephrotic syndrome is still unknown. This review discusses the role of the BAFF in the pathogenesis of nephrotic syndrome and highlights the gap of knowledge for future research.

Multimodal Screening for Pulmonary Arterial Hypertension in Systemic Scleroderma: Current Methods and Future Directions.

Systemic sclerosis (SSc) is an immuno-inflammatory rheumatic disease that can affect both the skin and internal organs through fibrosis. Pulmonary arterial hypertension (PAH) is one of the most severe secondary complications. Structural changes in the vascular bed lead to increased pressures in the pulmonary circulation, severely impacting the right heart and significantly affecting mortality. The gold standard for diagnosing PAH is right heart catheterization (RHC), an invasive method for measuring cardiac pressure. Due to the high risk of complications, procedural difficulties, and significant costs, non-invasive screening for SSc-PAH has garnered significant interest. Echocardiography is likely the most important screening tool, providing structural and functional information about the right heart through measurements that have proven their utility over time. In addition to imagistic investigations, serum biomarkers aid in identifying patients at risk for PAH and can provide prognostic information. Currently, well-known serum biomarkers (NT-proBNP, uric acid) are used in screening; however, in recent years, researchers have highlighted new biomarkers that can enhance diagnostic accuracy for SSc patients. Pulmonary involvement can also be assessed through pulmonary function tests, which, using established thresholds, can provide additional information and help select patients requiring RHC. In conclusion, given the invasiveness of RHC, non-invasive screening methods are particularly important for SSc patients.

Janus kinase inhibitor in combination therapy for atopic dermatitis

BACKGROUND: Atopic dermatitis is a chronic recurrent immunoinflammatory skin disease that develops against the background of a genotypic defect in the skin barrier function and innate and adaptive autoimmunity. Currently, there is no specific therapy for atopic dermatitis, so there remains a need to constantly search for effective pathogenetic approaches to its treatment. Today, the Janus kinase type 1 inhibitor abrocitinib is recommended for the treatment of moderate to severe atopic dermatitis. AIM: To conduct a comparative assessment of the effectiveness of the combination of UVB 311 nm with abrocitinib and UVB 311 nm phototherapy against the background of standard therapy according to indications in the treatment of patients with moderate and severe atopic dermatitis. MATERIALS AND METHODS: During the period from 2023 to 2024, the dermatological status and quality of life were assessed in 40 patients with moderate to severe atopic dermatitis who were prone to frequent relapses. The patients were treated at the clinic for skin and venereal diseases. Depending on the therapy, all patients were divided into two groups. The first group consisted of 20 patients receiving systemic, topical therapy in combination with UVB 311 nm phototherapy and additionally abrocitinib, at an induction dose of 200 mg followed by a dose of 100 mg. The second group included 20 patients who received systemic, local therapy in combination with UVB 311 nm phototherapy. Upon admission to the hospital and after two months of therapy, a comparative assessment of the DLQI index and an assessment of the prevalence and intensity of skin lesions in accordance with the SCORAD and IGA index were performed, an assessment of the level of IgE in the blood were performed RESULTS: After the course of therapy, the SCORAD index in patients of the first and second groups decreased statistically significantly (p=0.001) by 2.4 times and 1.6 times, respectively. The DLQI index in patients of the first and second groups after the course of therapy significantly (p=0.001) decreased by 3.2 times, 2.1 times, respectively. CONCLUSION: Our study revealed a more significant effectiveness of therapy with abrocitinib in combination with UVB 311 nm compared with UVB 311 nm monotherapy in patients with moderate and severe atopic dermatitis.

Novel DNA Aptamers to Dickkopf-1 Protein and Their Application in Colorimetric Sandwich Assays for Target Detection in Patients with Axial Spondyloarthritis.

Chronic immunoinflammatory rheumatic diseases, such as axial spondyloarthritis (AxSpA), are accompanied by a dysregulation of bone remodeling. Among potential biomarkers of bone metabolism, the Wnt pathway antagonist, Dickkopf-1 (DKK-1), is of particular interest because of its potential to reflect a shift towards joint ossification or osteoporosis, but its diagnostic value needs validation. There is still a lack of stable and efficient methods of measuring serum DKK-1 levels suitable for longitude studies. The use of aptamer-based diagnostic assays could be very promising for this purpose. We generated novel anti-DKK-1 DNA aptamers from a combinatorial library with a pre-defined sequence pattern in the randomized region. This approach showed high efficacy, as only four SELEX rounds of selection produced high-affinity aptamers with dissociation constants ranging from 1.3 to 3.7 nM. A family of their truncated versions was also developed by rational design. Novel DNA aptamers functioned as capture components in a microplate ELISA-like assay with HRP-conjugated anti-DKK-1 antibody as a reporter component. We succeeded in revealing the aptamer/aptamer sandwich pairs that provided an aptamer-only sandwich colorimetric assay. The aptamer/antibody colorimetric test systems were also examined in the analyses of blood serum from AxSpA patients and shown sufficient workability. However, in a number of cases we registered significant differences between assays based on TD10 and DK4 aptamers and made some suggestions about the origin of this effect.

Serotonin and adrenaline as inhibitors of neutrophil extracellular traps formation (experimental study)

Regulation of the NETosis can provoke cancer, inflammatory and autoimmune diseases and become a basis for effective targeted therapy. The aim: to study the modifying effects of serotonin and adrenaline on NETosis during phagocytosis in rats.Materials and methods.Wistar rats were divided into control (solvent, 0.9% NaCl solution) and experimental (serotonin and adrenaline 1.43 and 0.143 mg/kg body weight, respectively) groups. Intraperitoneal injection of test substances was carried out 90 minutes before blood sampling, in which phagocytic activity (PhA), phagocytic index (PhI) and degree of suicidal neutrophil NETosis were determined: with total and partial chromatin decondensation (TCD, PCD, accordingly). A paired Student’s t test was used to compare groups with numerical values and McNemar’s test (for dichotomous variables). Pearson’s linear correlation coefficient (rxy) was assessed to measure a linear relationship between time points.Results.The administration of adrenaline contributed to NETosis inhibition by 41.5% compared to control group (p 0.001), serotonin — by 27.6% (p 0.001). The ratio of neutrophils with total and partial chromatin decondensation for control group was 1.0:0.9; for serotonin and adrenaline it changed to 1.0:1.7 and 1.0:1.4, respectively. Relative to control group, phagocytic index after serotonin administration increased by 4.9%, in case of adrenaline, on the contrary, it decreased by 12.4% (p 0.01). A high positive correlation was revealed between NETosis and phagocytic index for control group and experimental group with adrenaline: rxy= 0.823–0.997. For phagocytic index and NETosis in these groups there was a high negative (rxy= –0.714–(–0.871)) and a noticeable positive correlation for serotonin (rxy= 0.638).Conclusion.Serotonin and adrenaline in therapeutic dosages have a pronounced inhibitory effect on NETosis, which may pave the avenue for increasing the effectiveness of therapy for immunoinflammatory and oncological diseases. The use of serotonin is preferable because it has additional immunomodulatory effects and cause no direct stimulation ofα- andβ-adrenergic receptors.

Marine ecosystems may offer environmental drugs for interventions in immunoinflammatory rheumatic diseases

Marine ecosystems may offer environmental drugs for interventions in immunoinflammatory rheumatic diseases

Are seronegative patients with rheumatoid arthritis and clinically suspect arthralgia properly represented in randomized clinical trials?

Rheumatoid arthritis (RA) is a chronic immuno-inflammatory disease whose outcomes can vary greatly from one patient to another. One of the main prognostic factors is the presence of serum autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). Indeed, when seropositive, patients with RA are at higher risk of radiographic progression, disability, and increased mortality. Moreover, while the introduction of the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria has allowed for an earlier diagnosis, studies on large early arthritis cohorts have also shown that these criteria are less capable of identifying seronegative patients, who are therefore at a higher risk of being diagnosed and treated late. In light of these, the major randomized controlled trials have mostly enrolled patients with autoantibody-positive disease. However, in recent years, it became evident that the two serotypes of RA differ significantly from many points of view. Alongside this, a greater understanding of the disease pathogenesis, particularly the presence of antibodies in patients' serum even before the onset of arthritis, has generated significant interest in exploring whether the disease could be prevented by treating patients in the pre-arthritis phases. Once again, emerging trials predominantly enroll subjects positive for RA autoantibodies, potentially overlooking seronegative individuals with arthralgia-at-risk.

Use of rituximab in the of immunoinflammatory rheumatic diseases combined with Graves' disease (autoimmune polyglandular syndrome in adults): case report and literature review

Rituximab (RTM) is a chimeric (murine and human) monoclonal antibody against B-lymphocytes (CD20). RTM is widely used in hematology for lymphoproliferative diseases and in rheumatology for rheumatoid arthritis, Sjögren's disease, some types of vasculitis and systemic connective tissue diseases. The administration of RTM is associated with a depletion of B-cells mediated by the regulation of apoptosis and cytotoxic effects via complement-dependent and antibody-dependent mechanisms. Considering the pathogenesis of autoimmune damage in Graves' disease (GD), an autoimmune thyroid disease associated with thyrotoxicosis, the use of RTM could be effective in this pathology. We present three patients with a combination of diffuse toxic goiter and rheumatic pathology treated with RTM; different outcomes of GD were observed.

A novel variant BCL11B mutation in a pediatric patient with difficult-to-treat eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is an immunoinflammatory disease of the esophagus attributable to a complex interaction between genetic and environmental factors. While several genetic risk variants have been linked with EoE, we report a novel association between B-cell lymphoma/leukemia 11B genetic mutation in a child with dysmorphic facies, developmental delays, atopic comorbidities, and difficult-to-treat EoE. After a prolonged course of EoE and multiple esophagogastroduodenoscopies with biopsies, this patient achieved clinical and histologic remission on a combination of swallowed topical steroids and high-dose proton pump inhibitor (PPI) therapy. However, her EoE relapsed when we attempted to wean her off PPI, and it was finally controlled after adding PPI back to her regimen. This report underscores the importance of genetic testing in patients with unusual clinical features and difficult-to-treat EoE. Relevant to real-world clinical practice, this case also raises the question of the treatment goals in children with EoE and underlying genetic mutation(s).

Immunomodulatory Effects and Regulatory Mechanisms of (R)-6-HITC, an Isothiocyanate from Wasabi (Eutrema japonicum), in an Ex Vivo Mouse Model of LPS-Induced Inflammation.

The present study aimed to investigate the effects of (R)-(-)-1-isothiocyanato-6-(methylsulfinyl)-hexane [(R)-6-HITC], the major isothiocyanate present in wasabi, in an ex vivo model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. (R)-6-HITC improved the immune response and mitigated oxidative stress, which involved suppression of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines (IL-1β, IL-6, IL-17, IL-18, and TNF-α) production and downregulation of pro-inflammatory enzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1. In addition, (R)-6-HITC was able to activate the Nrf2/HO-1 axis while simultaneously inhibiting key signaling pathways, including JAK2/STAT3, mitogen-activated protein kinases, and canonical and noncanonical inflammasome pathways, orchestrating its potent immunomodulatory effects. Collectively, these findings demonstrate the potential of (R)-6-HITC as a promising nutraceutical for the management of immuno-inflammatory diseases and justify the need for further in vivo validation studies.

Prevalence of co-morbidities among periodontitis and non-periodontitis Indian patients.

Periodontitis being an immuno-inflammatory disease can act as an aggravating factor for various systemic diseases. Therefore, it is of interest to document the prevalence of comorbidities among periodontitis and non-periodontitis Indian patients. 680 patients were enrolled, categorized into non-periodontitis group (Group A) and periodontitis group (Group B). Each group was again sub-grouped into comorbidities and non-co-morbidities. Periodontitis patients were found to have significantly more co-morbidities than non-periodontitis patients. Osteoporosis and obesity showed statistically higher levels in periodontitis patients. Hypertension, diabetes mellitus, cardiovascular diseases, and COVID-19 infection showed higher prevalence in periodontitis group, though the difference was statistically non-significant.

Pro-inflammatory activation of monocytes in patients with immunoinflammatory rheumatic diseases

Pro-inflammatory activation of monocytes in patients with immunoinflammatory rheumatic diseases

Proinflammatory Activation of Monocytes in Patients with Immunoinflammatory Rheumatic Diseases.

. The objective of this study was to evaluate the proinflammatory activation of circulating monocytes in patients with IRDs. . The study involved 149 participants (53 patients with rheumatoid arthritis (RA), 45patients with systemic lupus erythematosus (SLE), 34 patients with systemic scleroderma (SSc), and 17participants without IRDs) 30 to 65 years old. Basal and lipopolysaccharide (LPS)-stimulated secretion of monocytes was studied in a primary culture of monocytes obtained from blood by immunomagnetic separation. Quantitative assessment of the cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), as well as the chemokine monocyte chemoattractant protein-1 (MCP-1) was carried out in the culture fluid by ELISA. Proinflammatory activation of monocytes was calculated as the ratio of LPS-stimulated and basal secretions. . It was shown that the basal secretion of all studied cytokines was significantly increased in all groups of patients with IRDs, except for the secretion of IL-1β in the SLE group, compared to the control. LPS-stimulated secretion of TNF-α was increased and MCP-1 was decreased in patients with IRDs compared to the control group; LPS-stimulated IL-1β secretion only in the SSc group significantly differed from the control group. In the RA group, monocyte activation was reduced for all cytokines compared to the control; in the SLE group, for TNF-α and MCP-1; in the SSc group, for MCP-1. . The decrease in proinflammatory activation of monocytes in patients with IRDs is due to a high level of basal secretion of cytokines, which can lead to disruption of the adequate immune response in these diseases and is an important link in the pathogenesis of chronic inflammation.

Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis

To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Clinical cases of vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA vasculitis) induced by COVID-19

COVID-19 is similar to immunoinflammatory rheumatic diseases in clinical manifestations, immune responses and pathogenetic mechanisms. Specific autoantibodies as markers of autoimmune diseases can be detected in patients with coronavirus infection. Most often, after COVID-19, antinuclear antibodies, antibodies to phospholipids, to cardiolipin, to β2-glycoprotein, to cytoplasmic antigens SS-A and SS/B, and cyclic citrulline-containing peptide are detected. In moderate and severe cases of COVID-19 infection with pulmonary-renal syndrome, cytokine storm, antineutrophil cytoplasmic antibodies, antibodies to myeloperoxidase and to proteinase 3 have become more frequent, which can trigger neutrophil NETosis with the formation of extracellular neutrophil traps — networks and induce the development of autoimmune processes and the appearance of de novo immunoinflammatory rheumatic diseases: arthritis , systemic lupus erythematosus, vasculitis associated with antineutrophil cytoplasmic antibodies (ANCA vasculitis). Our study presents 4 clinical cases of patients with ANCA vasculitis with a history of recent coronavirus infection, chronologically verified. The average time after COVID-19 and the onset of ANCA vasculitis was about 3 months; damage to the upper respiratory tract, lower respiratory tract, skin and renal syndromes were observed. The severity of ANCA vasculitis did not depend on the severity of coronavirus infection: a mild course of COVID-19 infection did not exclude a severe course of ANCA vasculitis. It is recommended that all patients during and after coronavirus infection with post-COVID syndrome in the presence of damage to the ENT organs, kidneys, and skin are screened the presence of antineutrophil cytoplasmic antibodies to exclude the onset of ANCA vasculitis.

Clinical Significance of Antibodies to DFS70 in Immunoinflammatory Rheumatic Diseases.

The relevance of the problem of immunoinflammatory rheumatic diseases(IIRD) for modern medicine is determined by their high prevalence in the population, the difficulty of early diagnosis, the rapid development of disability and poor life prognosis. Recent data on the significance of anti-DFS70 have opened up new possibilities for optimizing the step-by-step diagnosis of IIRD. The detection of these antibodies can help in the interpretation of a positive result for antinuclear antibodies (ANA) by indirect immunofluorescence assay on HEp-2 cells (IIFA-HEp-2) in the absence of autoantibodies specific for IIRD. Detection of anti-DFS70 in antinuclear factor (ANF) seropositive patients without clinical and/or serological markers characteristic of a certain disease from the IIRD group can be considered as a potential marker that excludes this group of diseases.

Standing the test of COVID-19: charting the new frontiers of medicine

The COVID-19 pandemic accelerated research and innovation across numerous fields of medicine. It emphasized how disease concepts must reflect dynamic and heterogeneous interrelationships between physical characteristics, genetics, co-morbidities, environmental exposures, and socioeconomic determinants of health throughout life. This article explores how scientists and other stakeholders must collaborate in novel, interdisciplinary ways at these new frontiers of medicine, focusing on communicable diseases, precision/personalized medicine, systems medicine, and data science. The pandemic highlighted the critical protective role of vaccines against current and emerging threats. Radical efficiency gains in vaccine development (through mRNA technologies, public and private investment, and regulatory measures) must be leveraged in the future together with continued innovation in the area of monoclonal antibodies, novel antimicrobials, and multisectoral, international action against communicable diseases. Inter-individual heterogeneity in the pathophysiology of COVID-19 prompted the development of targeted therapeutics. Beyond COVID-19, medicine will become increasingly personalized via advanced omics-based technologies and systems biology—for example targeting the role of the gut microbiome and specific mechanisms underlying immunoinflammatory diseases and genetic conditions. Modeling proved critical to strengthening risk assessment and supporting COVID-19 decision-making. Advanced computational analytics and artificial intelligence (AI) may help integrate epidemic modeling, clinical features, genomics, immune factors, microbiome data, and other anthropometric measures into a “systems medicine” approach. The pandemic also accelerated digital medicine, giving telehealth and digital therapeutics critical roles in health system resilience and patient care. New research methods employed during COVID-19, including decentralized trials, could benefit evidence generation and decision-making more widely. In conclusion, the future of medicine will be shaped by interdisciplinary multistakeholder collaborations that address complex molecular, clinical, and social interrelationships, fostering precision medicine while improving public health. Open science, innovative partnerships, and patient-centricity will be key to success.

Efficacy and Safety of Crisaborole Ointment 2% in Chinese Patients Aged ≥ 2 Years with Mild to Moderate Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic immuno-inflammatory skin disease. Crisaborole ointment, 2%, is a nonsteroidal phosphodiesterase 4 inhibitor approved for the treatment of mild to moderate AD. This post hoc analysis assesses the efficacy and safety of crisaborole in Chinese patients aged ≥ 2years with mild to moderate AD. We evaluated the efficacy and safety of crisaborole in Chinese patients from the vehicle-controlled, phase 3 CrisADe CLEAR study. Patients were randomly assigned 2:1 to receive crisaborole or vehicle twice daily, respectively, for 28days. The primary endpoint was percent change from baseline in Eczema Area and Severity Index (EASI) total score at day 29. Key secondary endpoints were improvement in Investigator's Static Global Assessment (ISGA), ISGA success, and change from baseline in weekly average Peak Pruritus Numerical Rating Scale (PP-NRS) score. Adverse events were documented. Of 391 patients in the overall study, 237 were from China, 157 assigned to crisaborole and 80 assigned to vehicle. A greater reduction in percent change from baseline in EASI total score at day 29 was shown in the crisaborole vs. vehicle group (least squares mean [LSM]: -66.34 [95% (confidence interval) CI -71.55 to -61.12] vs. -50.18 [95% CI -58.02 to -42.34]). Response rates for achievement of ISGA improvement (43.2% [95% CI 35.4-51.1] vs. 33.4% [95% CI 22.5-44.2]) and ISGA success (31.7% [95% CI 24.3-39.0] vs. 21.5% [95% CI 12.1-30.9]) at day 29 were higher in the crisaborole vs. vehicle group. A greater reduction in change from baseline in weekly average PP-NRS score at week 4 was observed in the crisaborole vs. vehicle group (LSM: -1.98 [95% CI -2.34 to -1.62] vs. -1.08 [95% CI -1.63 to -0.53]). No new safety signals were observed. Crisaborole was effective and well tolerated in Chinese patients aged ≥ 2years with mild to moderate AD. ClinicalTrials.gov, NCT04360187.

Methotrexate and immunogenicity of vaccines in patients with rheumatic diseases

Currently, methotrexate (MT) remains one of the immunosuppressive drugs most commonly used in rheumatology. However, its effect on the immunogenicity of vaccines has until recently been studied only to a limited extent, which has led to the lack of clear recommendations for the use of MT during vaccination. Significant progress was made during the COVID-19 pandemic due to the dynamic development of vaccine research, including in patients with immuno-inflammatory rheumatic diseases. The review presents data on the effect of MT on the immunogenicity of vaccines against influenza, pneumococcus, herpes zoster, tetanus/diphtheria/pertussis, yellow fever and COVID-19 (including humoral and cellular responses) in rheumatological patients. The necessity of observing certain time intervals during vaccination in the case of MT use has been demonstrated. The potential mechanisms by which MT influences the immunogenicity of vaccines are presented. The importance of further clinical studies is emphasized in order to assess the effect of MT therapy on the vaccine response and to develop methods for its optimization.