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ID PMID Title PublicationDate abstract
34191227 Associations between sarcoidosis, autoimmune diseases, and autoantibodies: a single-center 2022 May To describe the clinical manifestations, immunological features, and risk factors in patients with sarcoidosis complicated with autoimmune diseases (ADs) as well as determine the frequency of autoantibodies and possible correlation between autoantibodies and laboratory data. Patients with pathologically confirmed sarcoidosis at Beijing Chaoyang Hospital (China) between January 2017 and October 2020 were included. Age- and sex-matched patients who visited the rheumatology outpatient clinic without systemic or ADs were included as controls. Demographic, clinical, serological, and radiological data of sarcoidosis patients were recorded and analyzed. To exclude ADs, autoantibodies, such as antinuclear antibody, extractable nuclear antigen antibodies, and anti-cyclic citrullinated peptide antibody were assessed in controls. A total of 154 sarcoidosis patients (111 females; 72.1%) with a mean ± standard deviation age of 50.7 ± 10.3 years were included. Nineteen patients (12.3%) had ADs; Hashimoto's thyroiditis (n = 6) and Sjogren's syndrome (n = 4) were common. Age, globulin, immunoglobulin G, erythrocyte sedimentation rate (ESR), and C-reactive protein were significantly different between sarcoidosis patients with and without ADs. The ESR level might be a risk factor for sarcoidosis complicated with ADs (RR = 1.053; P = 0.018). Autoantibodies were detected in 29 patients (18.8%), and the frequency was significantly higher than that in controls (18.8% vs. 3%; P = 0.001). Sarcoidosis patients were more likely to have autoantibodies despite the absence of ADs (10.4% vs. 3%; P = 0.031). Age may be a risk factor for sarcoidosis patients presenting with autoantibodies (RR = 1.077; P = 0.042). An association was identified between ADs and sarcoidosis. The inflammatory indexes, such as ESR, IgG, and CRP, were significantly different between sarcoidosis patients with and without ADs. ESR might be a risk factor for the coexistence of ADs and sarcoidosis. Sarcoidosis patients were prone to being autoantibody-positive despite the absence of ADs, and age might be a risk factor for sarcoidosis presenting with autoantibodies.
29494057 Cyclosporine. 2022 Jan Cyclosporine is an immunosuppressive agent used to treat organ rejection post-transplant. It also has use in certain other autoimmune diseases, treatment of organ rejection in kidney, liver, and heart allogeneic transplants, rheumatoid arthritis when the condition has not adequately responded to methotrexate. Also, it is a second-line agent for ALS and graft vs. host disease. It also has other FDA and non-FDA-approved indications. This activity reviews the mechanism of action, adverse event profile, toxicity, dosing, pharmacodynamics, and monitoring of cyclosporine, pertinent for interprofessional team members in treating conditions where cyclosporine is indicated.
35611096 The Immunomodulatory Properties of Vitamin D. 2022 Mar Since its discovery, vitamin D was shown to have both immunostimulatory and immunomodulatory effects on the immune system. A growing body of evidence so far linked vitamin D deficiency with the development and severity of several systemic and organ specific autoimmune/inflammatory diseases, such as systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. In the present report, the multiple and diverse effects of vitamin D on the immune system are reviewed.
35096112 Wu-Teng-Gao External Treatment Improves Th17/Treg Balance in Rheumatoid Arthritis. 2022 Rheumatoid arthritis (RA) represents the consequence of an immune response of the body's immune system attacking healthy cells. This chronic inflammatory disorder has complicated pathogenesis. Traditional Chinese medicine (TCM) is well recognized as an effective therapy in treating RA and has been widely applied for centuries. Wu-Teng-Gao (WTG) is used as a representative natural herb formula in RA treatment in China, while its mechanisms are to be fully clarified. The present study attempted to explore mechanisms of WTG on RA treatment in a network pharmacological approach and verified using experiments in vitro. Following the establishment of a rat model of collagen-induced arthritis (CIA), WTG was applied externally on the metapedes of rats. HE staining was subsequently performed to visualize the pathological changes of synovium and bone. Simultaneously, flow cytometry was conducted to detect the cell ratio of T helper 17 (Th17) and Regulatory T cells (Treg) in splenic lymphocytes. Additionally, ELISA, qRT-PCR, and Western blot assays were adopted to determine expressions of RA-related factors in joints and serum. Results of network pharmacological analysis suggested that Th17 cell differentiation might serve as a potential signaling pathway of WTG therapy for RA. Animal experiments demonstrated that WTG ameliorated the articular inflammation and effectively inhibited the destruction of articular cartilage, and decreased Th17 and Treg cell ratios in CIA rats. Furthermore, WTG also greatly suppressed relevant levels of inflammatory cytokines (IL-17, TNF-α, IL-1, and IL-6) and RNAKL, whereas it elevated expressions of anti-inflammatory cytokines IL-10 and TGF-β. Our results confirmed that WTG might improve the imbalance of Th17/Treg cells in CIA animals through differentiation regulation, thus alleviating joint inflammation and bone destruction.
29262145 Boutonniere Deformity. 2022 Jan Boutonniere deformity describes a medical condition in which the finger is flexed at the proximal interphalangeal joint (PIP) and hyperextended at the distal interphalangeal joint (DIP). This is usually a result of trauma in the acute setting and is caused by a rupture of the PIP central slip. This results in damage to the extensor function of the affected digit. A boutonniere deformity can also result from laceration injury to the central slip and dorsal capsule.   Boutonniere deformities can also occur secondary to burn injury, with tension ischemia representing a possible etiology for tendon rupture.   Overall, Boutonniere deformities common represent sequela of inflammatory arthritides, such as rheumatoid arthritis.
35138588 Granulomatous Diseases of the Central Nervous System. 2022 Jan PURPOSE OF REVIEW: To discuss the pathophysiology, key clinical features, necessary diagnostic evaluation, and current treatment regimens for granulomatous diseases of the central nervous system. RECENT FINDINGS: The diagnosis and management of granulomatous disease of the central nervous system has been revolutionized by advances in diagnostic imaging. Nevertheless, tissue and/or cerebrospinal fluid (CSF) sampling remains necessary to establish the diagnosis in most cases. Establishing a specific diagnosis is critical because treatment selection needs to focus on the granulomatous process centering on either antibiotic or immunosuppressive agents. Particular for non-infectious granulomatous disease more aggressive immunotherapies may help in clinical outcome. There are multiple non-infectious and infectious etiologies for granulomatous disease of the central nervous system. Clinical manifestations result from local structural invasion of granulomas or granulomatous inflammation of the blood vessels and meninges. Rapid diagnosis and specific treatment is essential.
35023427 Adenosine receptor A2a blockade by caffeine increases IFN-gamma production in Th1 cells fr 2022 Jan 13 OBJECTIVE: Studies indicate that caffeine uptake may be a risk factor for rheumatoid arthritis (RA), but a definitive link between caffeine consumption and RA has not been established. This study aimed to investigate the interplay between caffeine, adenosine receptor A2a, and interferon-γ (IFN-γ) production in CD4(+) T cells from RA patients. METHOD: Peripheral blood mononuclear cells were obtained from the peripheral blood of healthy individuals and patients with RA. CD4(+) T cells were isolated using the magnetic activated cell sorting technique and cultured in vitro with caffeine or mock control. In addition, adenosine was used as a competitive inhibitor of caffeine. After 48 h, expression of IFN-γ and interleukin-17 (IL-17) was analysed by flow cytometry. Ex vivo expression levels of adenosine receptor A2a were also assessed. RESULTS: Caffeine promoted IFN-γ production in Th1 cells in vitro. Significantly higher concentrations of caffeine were required to increase IFN-γ levels in Th1 cells from healthy individuals compared to Th1 cells from patients with RA. Moreover, ex vivo levels of adenosine receptor A2a expression on CD4(+) T cells were significantly higher in RA than in healthy individuals. Caffeine-driven IFN-γ production was completely reversed by adenosine, a competitive agonist of adenosine receptor A2a. In contrast to IFN-γ, production of IL-17 was not affected by caffeine. CONCLUSION: Caffeine promotes IFN-γ production in Th1 cells from RA patients in vitro by competitive inhibition of adenosine receptor A2a. Excessive coffee consumption could contribute to T-cell activation and inflammation in RA.
35583389 Associations between IL-23R gene polymorphism (rs10889677 A/C) and ankylosing spondylitis 2022 May 18 OBJECTIVES: Autoimmune diseases are a kind of chronic diseases for which the immune system loses tolerance to autoantigens. This meta-analysis' purpose is to determine whether there exists a correlation between IL-23R polymorphism and common autoimmune diseases like ankylosing spondylitis (AS) and rheumatoid arthritis (RA). METHODS: We searched the relevant literatures up to September 2021 and used different effect models for meta-analysis. 95% confidence interval (95% CI) and odds ratio (OR) were used to determine the relationship between rs10889677 (A/C) polymorphism and AS as well as RA. Finally, to promote the reliability of results, the trial sequential analysis (TSA) has also been applied and we searched the data related to autoimmune diseases (AS, RA) on genome-wide association studies (GWAS). RESULTS: Generally, 31 studies were included. Rs10889677 (A/C) was significantly correlated with the susceptibility to AS and RA among the general individuals (p < .05). Moreover, there existed a relevance between allele A and AS as well as RA in Caucasians (p < .05). AA genotype increased the risk of autoimmune diseases in Mongolians. As a result, the robustness of meta-analysis has further been proved by TSA. CONCLUSION: IL-23R (rs10889677 A/C) A allele was a risk gene for AS and RA in the general population, especially in Caucasians. AA genotype increased the risk of AS and RA in Mongolians.
35579086 MicroRNA and interleukin 6 interplay in the adipose tissue of rheumatoid arthritis patient 2022 Apr 29 OBJECTIVES: MicroRNAs (miRs) are non-translated RNA sequences that elicit negative control over protein expression. The adipose tissue (AT) is considered the major producer of miRs and inflammatory interleukin 6 (IL-6). This study aims to investigate the relationship between production of IL-6 and miRs in AT. METHODS: IL-6 gene expression was analysed in RNA extracts from subcutaneous AT of 75 patients with rheumatoid arthritis (RA), with qPCR. Genome-wide profile of human miRs (2565 miRs, 96.6%) was analysed in 35 AT samples on 3D microarray. The miR-processing proteins Dicer, Drosha and DGCR8 were analysed with qPCR. In silico prediction of protein targets for the differentially expressed (DE) miRs (p<0.05; log2FC >±0.5) was conducted by DIANA software. Seven AT samples were stimulated in vitro with IL-6 or IL-6+IL-6R antibody tocilizumab and analysed for the miR processing proteins. RESULTS: We identified 30 DE miRs between AT with high and low IL-6 mRNA, of which 26 miRs were inversely related with IL-6 levels. DE miRs were predicted to interfere in oestrogen (p=0.001), FoxO (p=0.006) and insulin (p=0.03) signalling pathways. High expression of IL-6 in AT was associated with significantly higher expression of Dicer (p=0.04) and Drosha (p=0.04), while inhibition of IL-6 signalling with tocilizumab decreased the levels of total miRs processing enzymes (p=0.003). CONCLUSIONS: IL-6 mRNA production in AT has a negative effect on the miRs expression profile and it increases miR-production capacity.
35496313 High-Throughput Chinmedomics Strategy Discovers the Quality Markers and Mechanisms of Wuto 2022 Wutou decoction (WTD) is a traditional Chinese medicine prescription for the treatment of rheumatoid arthritis (RA), and this study systematically analyzed the metabolic mechanism and key pharmacodynamic components of WTD in RA rats by combining untargeted metabolomics and serum pharmacochemistry of traditional Chinese medicine to enrich the evidence of WTD quality markers (Q-markers) studies. WTD prevented synovial edema in RA rats and reduced tumor necrosis factor-alpha and interleukin 6 levels in rat serum, according to the results of an enzyme-linked immunosorbent examination and histopathological inspection. In model rats, pattern recognition and multivariate statistical analysis revealed 24 aberrant metabolites that disrupted linoleic acid metabolism, arachidonic acid metabolism, arginine and proline metabolism, etc. However, continued dosing of WTD for 28 days reversed 13 abnormal metabolites, which may be an important therapeutic mechanism from a metabolomic perspective. Importantly, 12 prototypical components and 16 metabolites from WTD were characterized in RA rat serum. The results of Pearson correlation analysis showed that aconitine, L-ephedrine, L-methylephedrine, quercetin, albiflorin, paeoniflorigenone, astragaline A, astragaloside II, glycyrrhetic acid, glycyrrhizic acid, licurazide, and isoliquiritigenin are the key pharmacological components that regulate the metabolism of RA rats, and they are identified as Q-markers. In sum, utilizing metabolomics and serum pharmacochemistry of traditional Chinese medicine, the metabolic mechanisms and Q-markers of WTD therapy in RA rats were revealed, providing a theoretical basis for the quality control investigation of WTD.
35309327 Dysregulation of Survivin-Targeting microRNAs in Autoimmune Diseases: New Perspectives for 2022 It has been well established that the etiopathogenesis of diverse autoimmune diseases is rooted in the autoreactive immune cells' excessively proliferative state and impaired apoptotic machinery. Survivin is an anti-apoptotic and mitotic factor that has sparked a considerable research interest in this field. Survivin overexpression has been shown to contribute significantly to the development of autoimmune diseases via autoreactive immune cell overproliferation and apoptotic dysregulation. Several microRNAs (miRNAs/miRs) have been discovered to be involved in survivin regulation, rendering the survivin-miRNA axis a perspective target for autoimmune disease therapy. In this review, we discuss the role of survivin as an immune regulator and a highly implicated protein in the pathogenesis of autoimmune diseases, the significance of survivin-targeting miRNAs in autoimmunity, and the feasibility of targeting the survivin-miRNA axis as a promising therapeutic option for autoimmune diseases.
35200120 Classification of rheumatoid arthritis into active or inactive with a modified Disease Act 2022 Feb 17 OBJECTIVES: To establish the value of a modified Disease Activity score with Optical Spectral Transmission score (DAS-OST) without joint counts but with a HandScan score, versus that of DAS28, to classify rheumatoid arthritis (RA) as active versus inactive, with as reference standard the rheumatologist's clinical classification. METHODS: RA patients with at least one HandScan and DAS28 measurement performed at the same visit were included. Data was extracted from medical records, as was the clinical interpretation as active or inactive RA by the rheumatologist. Logistic regression analyses were performed to calculate areas under the receiver operating characteristics (AU-ROC) curves. The clinical interpretation was used as reference standard in all analyses, and disease activity measures were used as predictor variables. The performance of predictor variables (AU-ROCs) was compared. RESULTS: The data of 1505 RA patients were used for analyses. The highest AU-ROC of 0.88 (95%CI 0.85-0.90) was shown for DAS28; AU-ROC of DAS-OST was 0.78 (95%CI 0.75-0.81), difference 0.10, p<0.01. CONCLUSIONS: Compared to DAS28, DAS-OST classified RA statistically significantly less well as active versus inactive, when using the clinical classification as reference standard. However, a DAS-modification without joint scores might have a place in strategies limiting routine outpatients' visits to the rheumatologist.
35156626 Identifying physician-perceived barriers to a pragmatic treatment trial in rheumatoid arth 2022 Feb 14 OBJECTIVE: The aim of this qualitative research was to identify physician-perceived patient and clinic barriers to patient recruitment in a rheumatoid arthritis (RA) pragmatic trial of anti-tumor necrosis factor (TNF) biologic versus non-TNF biologic/Janus-Kinase inhibitor initiation after an inadequate response to methotrexate. METHODS: Semistructured telephone interviews were conducted with 26 rheumatologists in March 2019. An exploratory thematic analysis approach was used to analyze the interview data. RESULTS: Physician perceived patient barriers to the implementation of an RA pragmatic trial. This theme covers three subthemes: (1) patients' personal barriers, (2) patients' treatment-related factors, and (3) trial-related factors (eg, patient recruitment, side effects, mode of use, etc). Physicians perceived clinic barriers interfered with the pragmatic trial enrollment from the clinic or the healthcare system perspective. This theme covered four subthemes: (1) clinic-related factors, (2) patient-related factors, (3) research personnel, and (4) facilitators (positive factors of the clinic). CONCLUSION: Our results from the inductive thematic analysis will help researchers understand the key patient and clinic/system factors/barriers that may influence pragmatic RA trial implementation. The themes suggest there are factors that can be modified (eg, coordinator effort needed, effective patient recruitment during clinic visits, provider engagement) and challenges to overcome (patient insurance status, busy clinic flow, and space issues including limited number of patient rooms). In summary, these themes provide a basis for our and other research teams to develop clinic-centered and patientcentered strategies to implement a pragmatic RA trial.
35118101 Single Cell RNA Sequencing in Autoimmune Inflammatory Rheumatic Diseases: Current Applicat 2021 Single cell RNA sequencing (scRNA-seq) represents a new large scale and high throughput technique allowing analysis of the whole transcriptome at the resolution of an individual cell. It has emerged as an imperative method in life science research, uncovering complex cellular networks and providing indices that will eventually lead to the development of more targeted and personalized therapies. The importance of scRNA-seq has been particularly highlighted through the analysis of complex biological systems, in which cellular heterogeneity is a key aspect, such as the immune system. Autoimmune inflammatory rheumatic diseases represent a group of disorders, associated with a dysregulated immune system and high patient heterogeneity in both pathophysiological and clinical aspects. This complicates the complete understanding of underlying pathological mechanisms, associated with limited therapeutic options available and their long-term inefficiency and even toxicity. There is an unmet need to investigate, in depth, the cellular and molecular mechanisms driving the pathogenesis of rheumatic diseases and drug resistance, identify novel therapeutic targets, as well as make a step forward in using stratified and informed therapeutic decisions, which could now be achieved with the use of single cell approaches. This review summarizes the current use of scRNA-seq in studying different rheumatic diseases, based on recent findings from published in vitro, in vivo, and clinical studies, as well as discusses the potential implementation of scRNA-seq in the development of precision medicine in rheumatology.
35130279 Elucidating the material basis and potential mechanisms of Ershiwuwei Lvxue Pill acting on 2022 Ershiwuwei Lvxue Pill (ELP, མགྲིན་མཚལ་ཉེར་ལྔ།), a traditional Tibetan medicine preparation, has been used hundreds of years for the clinical treatment of rheumatoid arthritis (RA) in the highland region of Tibet, China. Nevertheless, its chemical composition and therapeutic mechanism are unclear. This study aimed to uncover the potentially effective components of ELP and the pharmacological mechanisms against RA by combing UPLC-Q-TOF/MS and network pharmacology. In this study, 96 compounds of ELP were identified or tentatively characterized based on UPLC-Q-TOF/MS analysis. Then, a total of 22 potential bioactive compounds were screened by TCMSP with oral bioavailability and drug-likeness. Preliminarily, 10 crucial targets may be associated with RA through protein-protein interaction network analysis. The functional enrichment analysis indicated that ELP exerted anti-RA effects probably by synergistically regulating many biological pathways, such as PI3K-Akt, Cytokine-cytokine receptor interaction, JAK-STAT, MAPK, TNF, and Toll-like receptor signaling pathway. In addition, good molecular docking scores were highlighted between five promising bioactive compounds (ellagic acid, quercetin, kaempferol, galangin, coptisine) and five core targets (PTGS2, STAT3, VEGFA, MAPK3, TNF). Overall, ELP can exert its anti-RA activity via multicomponent, multitarget, and multichannel mechanisms of action. However, further studies are needed to validate the biological processes and effect pathways of ELP.
34919889 Tofacitinib enhances interferon-γ-induced expression of major histocompatibility complex 2022 Jan 15 Tofacitinib is the first selective Janus kinase (JAK) 1/3 inhibitor approved for the treatment of rheumatoid arthritis and has been demonstrated to exhibit its efficacy through suppression of lymphocyte activation. Although macrophages are critically involved in the pathogenesis of rheumatoid arthritis, little is known about the influence of tofacitinib on macrophage activation especially expression of major histocompatibility complex class II (MHC II) and co-stimulatory molecule CD86. In the present study, we examined the effect of tofacitinib on the expression of MHC II and CD86 in RAW264.7 murine macrophages. Interferon (IFN)-γ induces the cell surface expression of MHC II and CD86. The treatment of tofacitinib at 0.5 μM significantly upregulated IFN-γ-induced expression of MHC II, while decreased the expression of CD86. Hence the population of CD86(-) MHC II(+) cells that induced by tofacitinib at 0.5 μM in the presence of IFN-γ were approximately three times larger than that of IFN-γ alone. Consistent with the surface expression, tofacitinib enhanced IFN-γ-induced mRNA expression of MHC II, and contrarily, decreased that of CD86. Similarly, tofacitinib increased the mRNA expression of MHC II transactivator (CIITA), especially CIITA type I, which is a key regulator of MHC II gene transcription. These findings suggested that tofacitinib enhanced IFNγ-induced MHC II expression by transcriptional regulation through induction of CIITA in macrophages and raise the possibility that a novel action of tofacitinib.
35646142 Needle-Warming Moxibustion plus Multirehabilitation Training to Improve Quality of Life an 2022 OBJECTIVE: Patients treated with medication for rheumatoid arthritis (RA) often improve but continue to have active diseases. The study aims to investigate whether needle-warming moxibustion (NWM) plus multirehabilitation training can improve quality of life (QoL) and functional mobility of RA patients after medication. METHODS: Eighty-four RA patients were selected as study participants, including 42 patients receiving medication (medication group) and 42 patients receiving NWM plus multirehabilitation training (NWM + MRT group). The scores of disease symptoms, pain (visual analogue scale (VAS)), sleep quality (Pittsburgh Sleep Quality Index (PSQI)), functional mobility (Fugl-Meyer assessment scale (FMAS)), self-rating anxiety scale (SAS), self-rating depression scale (SDS), and QoL (SF-36) were compared before and after treatment. When patients were discharged from the hospital, they were given a questionnaire for treatment satisfaction. RESULTS: After treatment, decreases in the scores of the VAS, PSQI, SAS, and SDS were observed in both cohorts, especially in the NWM + MRT group (P < 0.05). The FMAS scores of upper limbs and lower limbs were increased after treatment, which were higher in the NWM + MRT group in comparison with the medication group (P < 0.05). Of note, patients in the NWM + MRT group scored higher in various dimensions of the SF-36 scale (P < 0.05), showing better QoL. The satisfaction survey showed that the NWM + MRT group had a higher proportion of patients being satisfied and a lower proportion of patients being dissatisfied (P < 0.05). CONCLUSION: NWM plus multirehabilitation training could significantly attenuate disease symptoms, improve QoL, recover functional mobility, and reduce the risk of anxiety and depression in RA patients.
35649486 Curcumin-based nanotechnology approaches and therapeutics in restoration of autoimmune dis 2022 May 29 Autoimmune diseases usually arise as a result of an aberrant immune system attack on normal tissues of the body, which leads to a cascade of inflammatory reactions. The immune system employs different types of protective and anti-inflammatory cells for the regulation of this process. Curcumin is a known natural anti-inflammatory agent that inhibits pathological autoimmune processes by regulating inflammatory cytokines and their associated signaling pathways in immune cells. Due to the unstable nature of curcumin and its susceptibility to either degradation, or metabolism into other chemical entities (i.e., metabolites), encapsulation of this agent into various nanocarriers would appear to be an appropriate strategy for attaining greater beneficial effects from curcumin as it pertains to immunomodulation. Many studies have focused on the design and development of curcumin nanodelivery systems (micelles, dendrimers, and diverse nanocarriers) and are summarized in this review in order to obtain greater insight into novel drug delivery systems for curcumin and their suitability for the management of autoimmune diseases.
35391579 [Role of innate receptors in chronic inflammation and autoimmunity]. 2022 Apr 7 Elucidating the basis of chronic disease courses and the development of appropriate treatment methods for inflammatory diseases still represent a big challenge for medical science, as the mechanisms driving aberrant immune reactions are mostly still unknown. Of particular interest is the identification of checkpoints that regulate the function and differentiation of proinflammatory cells during the pathogenesis, along with methods for modulation of specific checkpoints as a treatment approach. Innate receptors, such as members of the natural killer group 2 family (NKG2X), natural cytotoxicity receptors (NCR) or Toll-like receptors (TLRs), play an important role in modulating the immune response. NKG2 member D (NKG2D) is a potent activating receptor of the immune system, known as a sentinel for cellular danger signals presented by cells exposed to endoplasmic reticulum (ER) stress, cell death or an inflammatory cytokine milieu. NKG2A/C bind the non-classical HLA class I molecule, sense changes in ligand expression associated with malignant transformation and cellular stress and their main function is to send inhibitory or activating signals to NK cells and subsets of T cells. In this review, we present our latest knowledge on the understanding of the role of innate receptors in the context of chronic inflammation and autoimmunity with special emphasis on danger sensor receptors NKG2D and NKG2A/C.
35094050 Humoral immunogenicity of COVID-19 vaccines in patients with inflammatory rheumatic diseas 2022 Jan 30 OBJECTIVES: Patients with inflammatory rheumatic diseases (IRD) treated with the monoclonal anti-CD20 antibody rituximab (RTX) have been identified as high-risk for severe COVID-19 outcomes. Additionally, there is increased risk due to reduced humoral immune response, induced by therapeutic B cell depletion. This study sought to quantify humoral response after vaccination against SARS-CoV-2 in patients with IRD treated with RTX. It also sought to elucidate the influence of timeframe between the last RTX dose and the first vaccination or the status of B cell depletion on antibody titre. METHODS: In this case-control study patients with IRDs previously treated with RTX were examined for humoral immune response after completing the first series of vaccinations with approved vaccines (BNT162b2 (Biontech/Pfizer), RNA-1273 (Moderna), (AstraZeneca/Oxford), Ad26.COV2.S (Janssen/Johnson & Johnson). Antibody levels were quantified using the Euroimmun Anti-SARS-CoV-2 QuantiVac ELISA [EI-S1-IgG-quant]. Blood samples were taken just before the next infusion with RTX after the vaccination. The interval between the last RTX infusion and the first vaccination against SARS-CoV-2 and other possible influencing factors on the antibody levels were evaluated. RESULTS: 102 patients were included. 65 (64%) showed a negative antibody level (<24IE/ml) after the vaccination. The comparative univariate analysis of the antibody levels achieved a significant result (p= 0.0008) for the time between last RTX infusion and first vaccination against SARS-CoV-2. No CD19+ peripheral B-cells could be measured in 73 of the patients (72%). CONCLUSION: The study confirms the negative impact of RTX on antibody level after vaccination against SARS-CoV-2. A clear relationship exists between antibody titre and interval of the last infusion to the first vaccination, number of peripheral B-cells and immunoglobulin quantity. These parameters help improve synchronization of vaccination and RTX therapy regimen.