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Clinical and Experimental Immunology May 2024This paper aims to compare the cellular immune response to the SARS-CoV2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD)...
This paper aims to compare the cellular immune response to the SARS-CoV2 BNT162b2 vaccine of pediatric patients with autoimmune inflammatory rheumatic disease (pAIIRD) and healthy controls. A prospective longitudinal study was conducted between April 2021 to December 2022 at the Tel Aviv Medical Center. Children<18 years, with pediatric-onset AIIRD and healthy controls, who have received at least two doses of the BNT162b2 vaccine, were included. Humoral response was evaluated by serum levels of anti-SARS-CoV-2 receptor-binding domain antibodies. Cellular response was evaluated by flow cytometry, measuring IFNγ and TNFα production by CD4+ T-cells following stimulation with SARS-CoV-2 Spike peptide mix. The study included 20 pAIIRD patients and 11 controls. The mean age of participants was 12.6±2.94 years, with 58.1% females. The cellular response to the BNT162b2 vaccine was statistically similar in both groups. However, the humoral response was statistically lower in pAIIRD compared with the healthy control group. There was no statistically significant correlation between the humoral response and cellular response. During the study period, 43.75% AIIRD children and 72.7% controls had a breakthrough COVID-19 infection (p=0.48). Bivariate models examining the effect of the cellular response and presence of an AIIRD on breakthrough infections found no effect. Compared with healthy controls, pAIIRD demonstrated similar cellular responses. Patients showed reduced humoral response compared with healthy adolescents, but similar breakthrough infection rates. These findings may support the importance of the cellular response in protecting against COVID-19 infections.
PubMed: 38767466
DOI: 10.1093/cei/uxae044 -
Clinical Pediatrics May 2024The antinuclear antibody (ANA) test is frequently used for the identification of patients who are at a high risk of developing autoimmune rheumatological diseases. The...
The antinuclear antibody (ANA) test is frequently used for the identification of patients who are at a high risk of developing autoimmune rheumatological diseases. The aim of this study is to evaluate the final diagnoses of patients applied to the pediatric rheumatology outpatient clinic with a positive ANA test result. In this study, the medical records of 283 children who had ANA positivity between January 2010 and January 2022 were evaluated retrospectively. All patients were younger than 18 years of age at diagnosis and were followed up in the pediatric rheumatology department for at least 6 months. The majority of the patients were females (69%), and the mean age was 9.9 ± 4.7 years. 94% of the ANA tests were requested in pediatric rheumatology outpatient clinics, and 6% in general pediatrics and other outpatient clinics. Arthritis was the most common reason for ANA testing (41.7%). Of the patients who had ANA positivity, 37% were diagnosed with juvenile idiopathic arthritis (JIA), 15% with connective tissue diseases, 10% with autoinflammatory disease, and 7% with vasculitides. Positivity at 1/320 and 1/640 titers were more common in the patients diagnosed with autoimmune connective tissue diseases or JIA compared to the patients without these diagnoses ( .009 and .013, respectively). The ANA test should be judiciously requested by pediatric rheumatologists, especially in suspected cases of autoimmune rheumatic disorders and JIA patients to aid in classification. Indiscriminate use of the ANA test for screening may potentially misguide clinicians.
PubMed: 38767305
DOI: 10.1177/00099228241254232 -
Journal of Paediatrics and Child Health May 2024This study aimed to examine the transition process of paediatric rheumatology patients from the Monash Children's Hospital (MCH) in Melbourne in order to identify areas...
AIM
This study aimed to examine the transition process of paediatric rheumatology patients from the Monash Children's Hospital (MCH) in Melbourne in order to identify areas that could be improved.
METHODS
Retrospective review of clinical data from the rheumatology database of paediatric rheumatology patients eligible for transition between January 2015 and September 2020.
RESULTS
One hundred and sixty-five patients were included; 57 patients were transitioned. Of patients transitioned to an adult service, 38 (88%) were on medication and 14 (33%) had active disease. All patients transitioned to the general practitioner (GP) had inactive disease off medication. Juvenile idiopathic arthritis (JIA) (non-systemic) was the most common diagnosis in patients transitioned. The mean age at which transition was first discussed was 18.0 years; the first referral was made at a mean of 18.3 years. The mean age at the first adult appointment was 18.5 years. Thirty-nine (91%) patients had a referral completed and 8 (19%) had a transfer letter. Thirteen (93%) patients transferred to the GP had a transfer letter. Transfer documents to an adult public rheumatology service rated 4.3 for quality, compared to 5.5 to the GP. Transfer of care was confirmed in 40 (93%) patients transitioned to an adult service; however, correspondence was available for only 3 (7%).
CONCLUSION
Although the transition process at MCH was adequate, it could be improved through earlier discussion of the process and improved referrals and documentation. A readiness-to-transfer checklist and a young adult clinic have the potential to improve the process of transition to adult rheumatology care.
PubMed: 38764198
DOI: 10.1111/jpc.16563 -
Mediterranean Journal of Rheumatology Mar 2024We have summarised the existing evidence supporting the concept that systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are part of the... (Review)
Review
AIM
We have summarised the existing evidence supporting the concept that systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease (AOSD) are part of the same Still's disease spectrum.
METHODS
A PubMed/Embase database search was conducted using specific search strings and free text words to screen for relevant articles. The search was limited to studies in humans, published up to June 2023, in English-language.
SUMMARY
sJIA and AOSD are rare autoinflammatory disorders that have similar pathophysiological and clinical features. The clinical presentations of sJIA and AOSD are highly variable, with differential diagnoses that include a broad range of malignancies, infectious diseases, and autoimmune disorders, which contribute to delays in diagnosis. Several sets of classification exist to help diagnose patients in clinical practice; the International League of Associations for Rheumatology criteria for sJIA and the Yamaguchi and Fautrel criteria for AOSD are the most-used criteria. The therapeutic strategy for Still's disease aims to relieve signs and symptoms, prevent irreversible joint damage and potentially life-threatening complications, and avoid deleterious side effects of treatment. Recently, targeted therapies such as interleukin (IL)-1 and IL-6 inhibitors have become available for the treatment of sJIA and AOSD. While these biologics were originally largely reserved for patients in whom non-steroidal anti-inflammatory drugs, corticosteroids and conventional synthetic disease-modifying anti-rheumatic drugs had failed, they are increasingly used earlier in the treatment paradigm. Among IL-1 inhibitors, canakinumab is the only biologic approved in the US for the treatment of both sJIA and AOSD.
PubMed: 38756937
DOI: 10.31138/mjr.290323.dat -
Nature Communications May 2024The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution....
The transition from natal downs for heat conservation to juvenile feathers for simple flight is a remarkable environmental adaptation process in avian evolution. However, the underlying epigenetic mechanism for this primary feather transition is mostly unknown. Here we conducted time-ordered gene co-expression network construction, epigenetic analysis, and functional perturbations in developing feather follicles to elucidate four downy-juvenile feather transition events. We report that extracellular matrix reorganization leads to peripheral pulp formation, which mediates epithelial-mesenchymal interactions for branching morphogenesis. α-SMA (ACTA2) compartmentalizes dermal papilla stem cells for feather renewal cycling. LEF1 works as a key hub of Wnt signaling to build rachis and converts radial downy to bilateral symmetry. Novel usage of scale keratins strengthens feather sheath with SOX14 as the epigenetic regulator. We show that this primary feather transition is largely conserved in chicken (precocial) and zebra finch (altricial) and discuss the possibility that this evolutionary adaptation process started in feathered dinosaurs.
Topics: Animals; Feathers; Chickens; Finches; Gene Expression Regulation, Developmental; Extracellular Matrix; Epigenesis, Genetic; Gene Regulatory Networks; Wnt Signaling Pathway; Keratins; Biological Evolution; Morphogenesis
PubMed: 38755126
DOI: 10.1038/s41467-024-48303-3 -
Modern Rheumatology May 2024This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA).
OBJECTIVES
This systematic review assessed the efficacy and safety of abatacept in patients with systemic juvenile idiopathic arthritis (JIA).
METHODS
Studies published between 2000 and 2021 were searched using PubMed, Embase, Cochrane, Ichushi-Web and clinical trial registries. The risk of bias was assessed according to the manual for development clinical practice guidelines by Minds, a project to promote evidence-based medicine in Japan.
RESULTS
Seven observational studies were included. American College of Rheumatology pediatric 30/50/70 responses at 3, 6 and 12 months were 64.8%/50.3%/27.9%, 85.7%/71.4%/42.9% and 80.0%/50.0%/40.0%, respectively. Outcomes on systemic symptoms, joint symptoms and activities of daily living were not obtained. No macrophage activation syndrome or infusion reaction occurred. Serious infection occurred in 2.6% of cases.
CONCLUSIONS
Abatacept improved the disease activity index. In addition, abatacept was as safe as interleukin-6 (IL -6) and IL-1 inhibitors. However, both the efficacy and safety data in this systematic review should be reviewed with caution because their quality of evidence is low or very low. Further studies are needed to confirm the efficacy and safety of abatacept for systemic JIA, especially its efficacy on joint symptoms.
PubMed: 38753302
DOI: 10.1093/mr/roae046 -
Frontiers in Molecular Biosciences 2024The pathogenesis of juvenile idiopathic arthritis (JIA) is strongly influenced by an impaired immune system. However, the molecular mechanisms underlying its development...
BACKGROUND
The pathogenesis of juvenile idiopathic arthritis (JIA) is strongly influenced by an impaired immune system. However, the molecular mechanisms underlying its development and progression have not been elucidated. In this study, the computational methods TRUST4 were used to construct a T-cell receptor (TCR) and B-cell receptor (BCR) repertoire from the peripheral blood of JIA patients bulk RNA-seq data, after which the clonality and diversity of the immune repertoire were analyzed.
RESULTS
Our findings revealed significant differences in the frequency of clonotypes between the JIA and healthy control groups in terms of the TCR and BCR repertoires. This work identified specific V genes and J genes in TCRs and BCRs that could be used to expand our understanding of JIA. After single-cell RNA analysis, the relative percentages of CD14 monocytes were significantly greater in the JIA group. Cell-cell communication analysis revealed the significant role of the MIF signaling pathway in JIA.
CONCLUSION
In conclusion, this work describes the immune features of both the TCR and BCR repertoires under JIA conditions and provides novel insight into immunotherapy for JIA.
PubMed: 38751447
DOI: 10.3389/fmolb.2024.1359235 -
JPMA. the Journal of the Pakistan... Apr 2024Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated,...
Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.
Topics: Humans; Female; Arthritis, Juvenile; Endomyocardial Fibrosis; Young Adult; Etanercept; Hypereosinophilic Syndrome; Echocardiography
PubMed: 38751280
DOI: 10.47391/JPMA.8648 -
The Journal of Craniofacial Surgery May 2024To evaluate and compare outcomes of patients with temporomandibular joint ankylosis (TMJA) treated by gap arthroplasty, costochondral graft, and total alloplastic joint...
AIM
To evaluate and compare outcomes of patients with temporomandibular joint ankylosis (TMJA) treated by gap arthroplasty, costochondral graft, and total alloplastic joint reconstruction.
METHODOLOGY
A retrospective cohort study reviewed and analyzed data from patients with TMJA from January 1, 2009 to December 31, 2019, at the Maxillofacial and Oral Surgery Department, University of the Witwatersrand. Patients with TMJA were treated either with gap arthroplasty, costochondral graft, or total alloplastic joint reconstruction. Data collected included age, sex, etiology of ankylosis, sides involved, preoperation and postoperation mouth opening (MO), treatment type, complications, and revision surgery. Patients were followed up for at least 18 months after the surgical procedure. Comparison of means across the treatment groups was analyzed using paired t tests or analysis of variance test. A P value of less than 0.05 was considered statistically significant.
RESULTS
The study sample comprised of 36 patients [bilateral, n=22; unilateral, n=14 (21 male, 15 female)]. Trauma was the most common etiology (n=27, 75%), followed by chronic infections (n=4, 11.11%) and juvenile arthritis (n=3, 8.3%). A paired t test revealed no statistical significance between treatment modality and postoperative MO and complications over 18 months (P=0.5316 and P=0.426, respectively). The mean MO increased from 4 to 28 mm. Reankylosis was the most common complication (n=5).
CONCLUSIONS
All 3 treatment options yield acceptable outcomes in patients with TMJA. Irrespective of surgical technique, early postoperative exercises, active physiotherapy, and follow-up are imperative for successful rehabilitation and prevention of reankylosis.
PubMed: 38743036
DOI: 10.1097/SCS.0000000000010223 -
Clinical Ophthalmology (Auckland, N.Z.) 2024Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice...
PURPOSE
Understanding sociodemographic factors associated with poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis may help inform practice patterns.
PATIENTS AND METHODS
Retrospective cohort study on patients <18 years old who were diagnosed with both juvenile idiopathic arthritis and uveitis based on International Classification of Diseases tenth edition codes in the Intelligent Research in Sight Registry through December 2020. Surgical history was extracted using current procedural terminology codes. The primary outcome was incidence of blindness (20/200 or worse) in at least one eye in association with sociodemographic factors. Secondary outcomes included cataract and glaucoma surgery following uveitis diagnosis. Hazard ratios were calculated using multivariable-adjusted Cox proportional hazards models.
RESULTS
Median age of juvenile idiopathic arthritis-associated uveitis diagnosis was 11 (Interquartile Range: 8 to 15). In the Cox models adjusting for sociodemographic and insurance factors, the hazard ratios of best corrected visual acuity 20/200 or worse were higher in males compared to females (HR 2.15; 95% CI: 1.45-3.18), in Black or African American patients compared to White patients (2.54; 1.44-4.48), and in Medicaid-insured patients compared to commercially-insured patients (2.23; 1.48-3.37).
CONCLUSION
Sociodemographic factors and insurance coverage were associated with varying levels of risk for poor visual outcomes in children with juvenile idiopathic arthritis-associated uveitis.
PubMed: 38741584
DOI: 10.2147/OPTH.S456252