Refractory hypereosinophilia associated with newly diagnosed rheumatoid arthritis following inactivated BBV152 COVID-19 vaccine.
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ABSTRACT:
SUBMITTER: Singh R
PROVIDER: S-EPMC9088458 | biostudies-literature | 2022 Aug
REPOSITORIES: biostudies-literature
Publications
Refractory hypereosinophilia associated with newly diagnosed rheumatoid arthritis following inactivated BBV152 COVID-19 vaccine.
Singh Rohit R Kaur Upinder U Singh Ankur A Chakrabarti Sankha S SS
Journal of medical virology 20220409 8
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Project description:ObjectivesTo longitudinally assesses pulmonary involvement in newly diagnosed rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients over a 12-months follow-up. To identify biomarkers and establish a diagnostic algorithm for monitoring pulmonary changes.MethodsNewly diagnosed RA and PsA patients were examined with clinical and laboratory assessments, pulmonary function tests (PFT), and chest radiography (CXR) at three-months intervals for one year.ResultsThe study enrolled 50 patients (26 RA, 24 PsA) and 26 controls. At baseline, 37.0% of arthritis patients (50.0% RA, 22.7% PsA) exhibited radiographic pulmonary involvement, with 64.7% being asymptomatic. No association was observed between CXR and PFTs. Reduced pathological breathing width was noted in 64.0% of patients (RA 69.2%, PsA 58.3%) and 23.1% of controls (p < .001). Thoracic excursion and lung auscultation showed no differences. During follow-up, PFT and physical examination findings remained stable. Mean CRP levels significantly decreased in RA patients from 23.5 mg/l (± 33.6; 95% CI: 9.9-37.1) to 2.7 mg/L (± 3.4; 95% CI: 1.0-4.3), and in PsA patients from 13.3 mg/L (± 18.0; 95% CI: 5.7-20.9) to 8.1 mg/L (± 16.2; 95% CI: 0.1-16.2) (p < .001). Additionally, significant reductions in disease activity scores and improvements in six-minute walking distance were observed (p < .001). No associations were identified between PFT outcomes, disease activity, or rheumatological medications throughout the disease course.ConclusionOur study underscores the prevalence of significant, predominantly asymptomatic pulmonary involvement in newly diagnosed RA and PsA patients. The lack of correlation between pulmonary function, disease activity, and medication during disease progression suggests that reducing arthritic disease activity does not necessarily mitigate the risk or severity of pulmonary involvement. Finally, our finding underscore the need for more sensitive biomarkers and optimized monitoring strategies.
| S-EPMC11655587 | biostudies-literature
Project description:Somatic mutations contribute to tumorigenesis. Although these mutations occur in all proliferating cells, their accumulation under non-malignant conditions, such as in autoimmune disorders, has not been investigated. Here, we show that patients with newly diagnosed rheumatoid arthritis have expanded CD8+ T-cell clones; in 20% (5/25) of patients CD8+ T cells, but not CD4+ T cells, harbour somatic mutations. In healthy controls (n=20), only one mutation is identified in the CD8+ T-cell pool. Mutations exist exclusively in the expanded CD8+ effector-memory subset, persist during follow-up, and are predicted to change protein functions. Some of the mutated genes (SLAMF6, IRF1) have previously been associated with autoimmunity. RNA sequencing of mutation-harbouring cells shows signatures corresponding to cell proliferation. Our data provide evidence of accumulation of somatic mutations in expanded CD8+ T cells, which may have pathogenic significance for RA and other autoimmune diseases.
| S-EPMC5482061 | biostudies-literature
Project description:Adiponectin, leptin, and resistin are adipocytokines whose levels are elevated in blood and synovial fluid from patients with rheumatoid arthritis (RA). However, their role in RA pathogenesis is unclear. Here, we examined whether adipocytokines are associated with circulating chemokines, markers of inflammation and RA disease activity in patients with untreated newly diagnosed RA. Plasma levels of 15 chemokines, adiponectin, leptin, and resistin were measured using flow cytometry bead-based immunoassay or enzyme-linked immunosorbent assay (ELISA) in a cohort of 70 patients with untreated newly diagnosed RA. Markers of inflammation and disease activity were also assessed in all patients. Positive association was found between total adiponectin and CXCL10 (β = 0.344, p = 0.021), CCL2 (β = 0.342, p = 0.012), and CXCL9 (β = 0.308, p = 0.044), whereas high-molecular weight (HMW) adiponectin associated only with CXCL9 (β = 0.308, p = 0.033). Furthermore, both total and HMW adiponectin were associated with C-reactive protein (β = 0.485, p = 0.001; β = 0.463, p = 0.001) and erythrocyte sedimentation rate (β = 0.442, p = 0.001; β = 0.507, p < 0.001). Leptin and resistin were not associated with plasma chemokines, markers of inflammation, or disease activity scores. Our study shows an association between circulating adiponectin and pro-inflammatory chemokines involved in RA pathogenesis as well as markers of inflammation in a well-characterized cohort of patients with untreated newly diagnosed RA.
| S-EPMC7924659 | biostudies-literature
Project description:The COVID-19 pandemic is a global health crisis that poses a great challenge to the public health system of affected countries. Safe and effective vaccines are needed to overcome this crisis. Here, we develop and assess the protective efficacy and immunogenicity of an inactivated SARS-CoV-2 vaccine in rhesus macaques. Twenty macaques were divided into four groups of five animals each. One group was administered a placebo, while three groups were immunized with three different vaccine candidates of BBV152 at 0 and 14 days. All the macaques were challenged with SARS-CoV-2 fourteen days after the second dose. The protective response was observed with increasing SARS-CoV-2 specific IgG and neutralizing antibody titers from 3rd-week post-immunization. Viral clearance was observed from bronchoalveolar lavage fluid, nasal swab, throat swab and lung tissues at 7 days post-infection in the vaccinated groups. No evidence of pneumonia was observed by histopathological examination in vaccinated groups, unlike the placebo group which exhibited interstitial pneumonia and localization of viral antigen in the alveolar epithelium and macrophages by immunohistochemistry. This vaccine candidate BBV152 has completed Phase I/II (NCT04471519) clinical trials in India and is presently in phase III, data of this study substantiates the immunogenicity and protective efficacy of the vaccine candidates.
| S-EPMC7925524 | biostudies-literature
Project description:ObjectivesTo evaluate the Medical Research Council (MRC) dyspnoea scale and serum Microfibrillar-associated protein 4 (MFAP4) levels for the detection of respiratory impairment in newly diagnosed rheumatoid arthritis (RA).MethodsPatients underwent blood tests, pulmonary function tests (PFT) and dyspnoea assessment using the MRC scale. Respiratory impairment was defined as a diffusion capacity of the lungs for carbon monoxide (DLCO) <80% predicted or FEV1/FVC <70%. The primary outcomes were the MRC and MFAP4's sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence intervals (CI).ResultsOne hundred and thirty-one patients had available baseline tests. Mean age was 57.7 years (SD: 10.9), 61% were female, and 45% had respiratory impairment. For MRC score ≥ 2, the sensitivity was 39.0% (95% CI 26.5; 52.6), specificity 76.4% (95% CI 64.9; 85.6), and DOR 2.07 (95% CI 0.97; 4.40). For MFAP4 > 29.0 U/mL, the sensitivity was 62.7% (95% CI 49.1; 75.0), specificity 56.9% (95% CI 44.7; 68.6), and DOR 2.22 (95% CI 1.10; 4.50). The DOR was 3.01 (95% CI 1.27; 7.16) for MFAP4 detecting respiratory impairment when adjusted for age, sex and smoking status.ConclusionThe MRC dyspnoea score and unadjusted MFAP4 levels were poor predictors of respiratory impairment in patients with early treatment-naïve rheumatoid arthritis.
| S-EPMC11749244 | biostudies-literature
Project description:Our objective was to estimate the percentage of patients with incident rheumatoid arthritis (RA) who were seen by a rheumatologist within 3, 6 and 12 months of suspected diagnosis by a family physician, and assess what factors may influence the time frame with which patients are seen.Ontario, Canada.Over 2000-2009, we studied patients with incident RA who were initially diagnosed by a family physician.We assessed secular trends in rheumatology encounters and differences between patients who received versus did not receive rheumatology care. We performed hierarchical logistic regression analyses to determine whether receipt of rheumatology care was associated with patient, primary care physician and geographical factors.Among 19 760 patients with incident RA, 59%, 75% and 84% of patients were seen by a rheumatologist within 3, 6 and 12 months, respectively. The prevalence of initial consultations within 3 months did not increase over time; however, access within 6 and 12 months increased over time. Factors positively associated with timely consultations included higher regional rheumatology supply (adjusted OR (aOR) 1.35 (95% CI 1.13 to 1.60)) and higher patient socioeconomic status (aOR 1.18 (95% CI 1.07 to 1.30)). Conversely, factors inversely associated with timely consultations included remote patient residence (aOR 0.51 (95% CI 0.41 to 0.64)) and male family physicians (aOR 0.88 (95% CI 0.81 to 0.95)).Increasing access to rheumatologists within 6 and 12 months occurred over time; however, consultations within 3 months did not change over time. Measures of poor access (such as proximity to and density of rheumatologists) were negatively associated with timely consultations. Additional factors that contributed to disparities in access included patient socioeconomic status and physician sex.
| S-EPMC3913026 | biostudies-literature
Project description:Extracellular vesicles (EVs) are implicated in rheumatoid arthritis (RA) but have mainly been assessed in RA patients taking disease modifying anti-rheumatic drugs. EVs are nanoparticles important in cell-cell communication and their molecular cargo are biomarker candidates. We characterized the protein profiles of EVs from blood plasma from newly diagnosed, treatment naïve RA patients (N=32) and compared them to healthy controls (N=20), by size exclusion chromatography-based EV enrichment coupled with high-resolution quantitative proteomics. The RA patients had higher EV concentration and larger EVs than controls. A total of 682 EV proteins were reliably quantified, and the overall profiles were distinctly different between patients and controls. Specifically, 26 proteins were significantly upregulated and 31 downregulated in RA patients, with several proteins acting in inflammatory networks and with immunologically important upstream regulators. The RA associated EVs appear, based on the tissue expression of their cargo proteins, to originate mainly from hepatocytes or immune cells, like neutrophils. Interestingly, the strongest RA associated EV proteins were inflammatory molecules, like SAA1 and S100A9, already suggested as biomarkers in RA. Furthermore, the RA associated EV proteins were generally not correlated with total serum protein levels, stressing the importance of EV transport of inflammatory proteins in RA pathogenesis.
2025-05-07 | PXD060460 | Pride
Project description:BackgroundTo mitigate the effects of COVID-19, a vaccine is urgently needed. BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a toll-like receptor 7/8 agonist molecule adsorbed to alum (Algel-IMDG) or alum (Algel).MethodsWe did a double-blind, multicentre, randomised, controlled phase 1 trial to assess the safety and immunogenicity of BBV152 at 11 hospitals across India. Healthy adults aged 18-55 years who were deemed healthy by the investigator were eligible. Individuals with positive SARS-CoV-2 nucleic acid and/or serology tests were excluded. Participants were randomly assigned to receive either one of three vaccine formulations (3 μg with Algel-IMDG, 6 μg with Algel-IMDG, or 6 μg with Algel) or an Algel only control vaccine group. Block randomisation was done with a web response platform. Participants and investigators were masked to treatment group allocation. Two intramuscular doses of vaccines were administered on day 0 (the day of randomisation) and day 14. Primary outcomes were solicited local and systemic reactogenicity events at 2 h and 7 days after vaccination and throughout the full study duration, including serious adverse events. Secondary outcome was seroconversion (at least four-fold increase from baseline) based on wild-type virus neutralisation. Cell-mediated responses were evaluated by intracellular staining and ELISpot. The trial is registered at ClinicalTrials.gov (NCT04471519).FindingsBetween July 13 and 30, 2020, 827 participants were screened, of whom 375 were enrolled. Among the enrolled participants, 100 each were randomly assigned to the three vaccine groups, and 75 were randomly assigned to the control group (Algel only). After both doses, solicited local and systemic adverse reactions were reported by 17 (17%; 95% CI 10·5-26·1) participants in the 3 μg with Algel-IMDG group, 21 (21%; 13·8-30·5) in the 6 μg with Algel-IMDG group, 14 (14%; 8·1-22·7) in the 6 μg with Algel group, and ten (10%; 6·9-23·6) in the Algel-only group. The most common solicited adverse events were injection site pain (17 [5%] of 375 participants), headache (13 [3%]), fatigue (11 [3%]), fever (nine [2%]), and nausea or vomiting (seven [2%]). All solicited adverse events were mild (43 [69%] of 62) or moderate (19 [31%]) and were more frequent after the first dose. One serious adverse event of viral pneumonitis was reported in the 6 μg with Algel group, unrelated to the vaccine. Seroconversion rates (%) were 87·9, 91·9, and 82·8 in the 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel groups, respectively. CD4+ and CD8+ T-cell responses were detected in a subset of 16 participants from both Algel-IMDG groups.InterpretationBBV152 led to tolerable safety outcomes and enhanced immune responses. Both Algel-IMDG formulations were selected for phase 2 immunogenicity trials. Further efficacy trials are warranted.FundingBharat Biotech International.
| S-EPMC7825810 | biostudies-literature
Project description:BackgroundTumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA.MethodsData on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model.ResultsOf the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255-0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235-0.797), breast cancer (0.146; 0.045-0.474), and genitourinary cancer (0.220; 0.059-0.820).ConclusionsThe use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.
| S-EPMC9364556 | biostudies-literature
Project description:BackgroundBBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.MethodsWe conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%.FindingsBetween April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61).InterpretationThis study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.FundingNone.TranslationFor the Hindi translation of the abstract see Supplementary Materials section.
| S-EPMC8610201 | biostudies-literature