Autoimmune Diseases In Children Research Articles

Adverse Event Profiles of Adalimumab in Children: A Disproportionality Analysis

Background: Adalimumab has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult rheumatoid arthritis (RA), and subsequently approved for pediatric treatment of various autoimmune diseases in children of different ages. Due to genetic differences between children and adults in terms of physiology and immunity, there is a need to explore the safety of adalimumab in children in the real world. The aim of this study is to identify potential adverse event (AE) signals associated with the use of adalimumab in pediatric patients (<18 years old) using data from the FDA Adverse Event Reporting System (FAERS). Methods: AEs associated with adalimumab in pediatric patients reported in the FAERS database from the first quarter (Q1) of 2017 to the third quarter (Q3) of 2022 were systematically gathered. Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the information component (IC), and the empirical Bayes geometric mean (EBGM) were used to assess the relationship between adalimumab and AEs in children. Results: Out of 8,363,304 reports collected from the FAERS database during the study period, 3819 reports on children on adalimumab were identified. Adalimumab-related AEs reports were concentrated on 10 toxicity areas and a total of 202 positive signals were detected, of which injection site papule (ROR = 261.97) and intestinal fistula (ROR = 122.09) had the strongest signals. Unexpected significant AEs, including intestinal obstruction, immunodeficiency, abdominal abscess, and Takayasu’s arteritis might also occur. In comparison with patients of all ages in the same time window, the median onset time of children was shorter (99 vs. 149 days). Most of the AE cases occurred in children within the first 1 (1.71%), 2 (8.12%), and 3 months (8.39%) and had early failure types after adalimumab initiation. Methotrexate, folic acid, prednisone, azathioprine, and mesalamine were the top five drugs used concomitantly for adalimumab-associated AEs. Conclusions: When adalimumab is used in children, especially in the first 3 months of treatment, in addition to the AEs recorded in the drug package insert, close attention should be paid to the new potential AEs off-label to ensure the safety of adalimumab in children.

Atopic diseases and the risk of alopecia areata among pre-teens and teenagers in Taiwan

Background Alopecia areata (AA), a disorder of non-scarring hair loss with a variable relapsing and remitting course, is a common autoimmune disease in children. Although it often presents as several focal small patchy bald lesions, early onset AA can lead to a total loss of scalp hair, even body hairs, a severe subtype. Atopic diseases are common concurrent disorders in AA, especially among those with early onset severe type of hair loss. Whether atopic diseases increase the risk of AA in the paediatric population of Taiwan, remains unclear. Objective To identify if atopic diseases increase the risk of AA among pre-teens and teenagers in Taiwan. Methods From Taiwan National Health Insurance Database 2010, we used the claims data to clarify the risk of AA in pre-teens and teenagers with atopic diseases (atopic dermatitis, allergic conjunctivitis, asthma, allergic rhinitis and food allergy) as compared to the general population. Cox proportional hazards model yielded hazard ratios (HRs) to address the impact of atopic diseases, sex and age on AA risk after adjusting for covariates and subsequent stratified analyses. Results Overall, 21,070 children (10,535 patients with atopic diseases and 10,535 normal cohort) aged over nine years were recruited. During a follow-up of 15 years, 39 (0.37%) cases were identified to have AA in the atopic diseases group, while 11 (0.10%) had developed AA in the normal cohort. As compared with the normal population, the paediatric population with atopic diseases had a 9.66-fold higher risk of developing AA. The risk was greater for boys and increased with advanced age. In the atopic diseases group, pre-teens and teenagers with food allergies and Sjogren’s syndrome were more likely to have AA. Limitations Only one ethnic group. Conclusion All atopic diseases enhanced the risk of developing AA in Taiwan pre-teens and teenagers. Children with atopic diseases should be monitored to look for the development of AA.

OA34 Unravelling the role of B cells and interferon dysregulation in juvenile dermatomyositis

Abstract Background/Aims Juvenile dermatomyositis (JDM) is a rare childhood autoimmune disease, characterised by muscle inflammation and skin rash. At present, the exact mechanisms driving JDM pathogenesis remain unclear. Recent investigations have focused on the potential roles of interferon (IFN) dysregulation and B cells. This study aims to explore alterations in B cell populations and their association with disease severity and IFN pathway dysregulation in JDM patients. Methods Transcriptomic, flow cytometry, and clinical data were gathered from a cohort of 61 JDM patients recruited from the UK JDCBS. Clinical demographics and disease variables were extracted from the JDCBS database. Flow cytometry was utilised to examine B cell populations in treatment naïve (‘pre-treatment’ n = 48) and JDM patients on steroids and conventional DMARD treatment, including rituximab (on-treatment n = 24), in parallel with age-matched healthy donors (n = 35). Transcriptomic analysis was performed on the total CD19+ B cells to assess their gene expression profiles in JDM patients. Pathway enrichment analysis was applied to identify the involvement of IFN-related pathways in JDM pathogenesis. Results Flow cytometry analysis revealed a significant expansion of total B cells, (defined as CD19+, p < 0.0001, ANOVA) and immature B cells (defined as CD19+ CD24hi CD38hi, p = 0.0416, Kruskal-Wallis) in pre-treatment JDM patients compared to healthy controls, which returned to levels similar to those in healthy donors in on-treatment JDM patients. An inverse relationship between total B cells and the Childhood Myositis Assessment Scale (CMAS), a measure of muscle strength, was observed in pre-treatment JDM patients, indicating a connection between the expanded B cell population and worse disease. Transcriptomic analysis of B cells illustrated distinctive clustering between pre-treatment JDM patients and healthy controls, based on their type I IFN gene expression profiles. Pathway enrichment analysis confirmed the significant enrichment of IFN-related pathways in B cells of pre-treatment JDM patients. Conclusion This study validates previous observations (Piper et al., 2018) supporting a significant role of B cells in the pathogenesis of JDM and their association with IFN dysregulation. Notably, pre-treatment JDM patients exhibited an expansion of the total B cell population, and of immature B cells, which correlated with disease activity and were restored to normal levels with treatment. Transcriptomic analysis identified distinct IFN-related gene profiles in B cells from pre-treatment JDM patients. These findings offer valuable insights into the complex autoimmune condition of JDM, potentially opening avenues for novel therapeutic strategies. Disclosure A.E.K. Syntakas: None. H.D. Nguyen: None. R. Restuadi: None. B.R. Jebson: None. V. Alexiou: None. L.R. Marshall: None. E. Ralph: None. K. O’Brien: None. D. Cancemi: None. H. Peckham: None. A. Radziszewska: None. N. De Gruijter: None. G.T. Hall: None. S. Castellano: None. C. Ciurtin: None. C.T. Deakin: None. E. Rosser: None. L.R. Wedderburn: None. M. Kartawinata: None. M.G.L. Wilkinson: None.

Bickerstaff encephalitis in childhood: a review of 74 cases in the literature from 1951 to today.

Bickerstaff brainstem encephalitis (BBE) is a rare autoimmune disease characterized by the subacute onset of bilateral external ophthalmoplegia, ataxia, and decreased level of consciousness. BBE is part of a group of rare autoimmune diseases in children that can affect the nervous system at any level. The onset of neurological deficits is often sudden and nonspecific. The diagnosis is based on clinical findings and abnormal findings on cerebrospinal fluid (CSF), electroencephalography (EEG), electromyography (EMG), and magnetic resonance imaging (MRI). BBE is associated with the presence of the antiganglioside antibody, anti-GQ1b and anti-GM1. Intravenous immunoglobulin (IVIg) and plasma exchange are often used as treatments for these patients. We conducted a review on clinical presentation, diagnosis, treatment and outcome of reported cases of BBE. 74 cases are reported in the literature from the first cases described in 1951 to today. The prevalence is unknown while the incidence is higher in males. In 50% of cases, BBE occurs following respiratory or gastrointestinal tract infections. The most frequent initial symptoms were consciousness disturbance, headache, vomiting, diplopia, gait disturbance, dysarthria and fever. During illness course, almost all the patients developed consciousness disturbance, external ophthalmoplegia, and ataxia. Lumbar puncture showed pleocytosis or cytoalbuminological dissociation. Abnormal EEG and MRI studies revealed abnormalities in most cases. Anti-GQ1b antibodies were detected in more than half of the patients; anti-GM1 antibodies were detected in almost 40% of patients. Treatment guidelines are missing. In our analysis, steroids and IVIg were administered alone or in combination; as last option, plasmapheresis was used. BBE has a good prognosis and recovery in childhood is faster than in adulthood; 70% of patients reported no sequelae in our analysis. Future studies need to investigate pathogenesis and possible triggers, and therapeutic possibilities.

Risk of immune-related diseases in childhood after intrapartum antibiotic exposure

Intrapartum antibiotic prophylaxis is effective in preventing early-onset group B streptococcal disease in newborn infants, but it influences gut microbiota development. Gut microbiota composition is, in turn, associated with immune-related diseases in childhood. This study hypothesized that intrapartum antibiotic exposure is associated with immune-related diseases in childhood. We conducted a population-based cohort study of vaginally delivered children. We retrieved data on intrapartum antibiotic exposure from structured electronic medical records and obtained outcome data on childhood autoimmune, allergic, and obstructive airway diseases from comprehensive national registers. We used Cox regression analysis with adjustment for maternal and neonatal covariates and regarded death as a competing risk in the analyses. The study population comprised 45,575 vaginally born children of whom 9733 (21%) had been exposed to intrapartum antibiotics. Intrapartum antibiotic exposure was associated with an autoimmune disease diagnosis (adjusted hazard ratio, 1.28; 95% confidence interval, 1.02-1.62), which corresponds to 22% (95% confidence interval, 6-39) as a theoretical population-attributable fraction. Intrapartum antibiotic exposure was not associated with diagnoses of allergic (adjusted hazard ratio, 1.08; 95% confidence interval, 0.97-1.20) or obstructive airway diseases (adjusted hazard ratio, 1.04; 95% confidence interval, 0.96-1.14). Intrapartum antibiotic exposure may be associated with an increased risk for autoimmune diseases in childhood. This finding supports the efforts to develop more specific group B streptococcal disease prevention strategies in the future.

CONSANGUINITY AS A SIGNIFICANT RISK FACTOR FOR DIABETES MELLITUS: A SYSTEMATIC REVIEW

Objectives:This systematic review aims to study the recent updates regarding the association between consanguinity and DM. Methods:PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Results& interpretation: Our results included ten studies with a total of 8878 patients, and 4565 (51.4%) were males. Eight studies included patients with T2D, and two included T1D. The prevalence of consanguinity ranged from 21.9% to 95% in T2D and 70.8% in T1D.PreoperThe development of T2D was significantly influenced by consanguinity, consanguineous marriages, and maternal diabetes, particularly in developing Arab countries where the prevalence of T2D in families is very high. Significant risk variables for T2D in MetS patients were consanguineous marriages, maternal aunts, maternal grandpas, and the presence of MetS in the parents family. A family history of autoimmune disease in children or paternal consanguinity is not strongly associated with the complexity of T1D.

CONSANGUINITY AS A SIGNIFICANT RISK FACTOR FOR DIABETES MELLITUS: A SYSTEMATIC REVIEW

Objectives:This systematic review aims to study the recent updates regarding the association between consanguinity and DM. Methods:PubMed, SCOPUS, Web of Science, and Science Direct were systematically searched for relevant literature. Rayyan QRCI was employed throughout this comprehensive process. Results& interpretation: Our results included ten studies with a total of 8878 patients, and 4565 (51.4%) were males. Eight studies included patients with T2D, and two included T1D. The prevalence of consanguinity ranged from 21.9% to 95% in T2D and 70.8% in T1D.PreoperThe development of T2D was significantly influenced by consanguinity, consanguineous marriages, and maternal diabetes, particularly in developing Arab countries where the prevalence of T2D in families is very high. Significant risk variables for T2D in MetS patients were consanguineous marriages, maternal aunts, maternal grandpas, and the presence of MetS in the parents family. A family history of autoimmune disease in children or paternal consanguinity is not strongly associated with the complexity of T1D.

Sjögren's Syndrome: A Rare Clinical Entity in Children

Background. Sjögren's syndrome (SS) is a rare autoimmune disease in children, with only a few hundred reported cases. Its clinical presentation is atypical. We report the case of a 14-year-old boy diagnosed with recurrent parotitis.
 Case Presentation. Our patient, a 14-year-old male, presented with a one-year history of recurrent bilateral parotid swellings. Clinical examination revealed an objective oculo-buccal dryness. Ultrasound imaging showed hypoechoic hypertrophy of the parotid glands. Anti-SSA/SSB antibodies were strongly positive. Histological study of the accessory salivary glands revealed lymphocytic sialadenitis with a focus score of 3. The diagnosis of SS was confirmed according to the ACR/EULAR 2016 criteria. The combination of treatment with hydroxychloroquine and corticosteroids resulted in the resolution of clinical signs and biological inflammatory markers.
 Conclusion. Given the rarity of SS in children, several diagnostic and therapeutic difficulties arise, in the absence of classification criteria adapted to the juvenile form of the disease, and the absence of therapeutic recommendations consolidated by clinical trials in children.

Galectin-1 correlates with inflammatory markers and T regulatory cells in children with type 1 diabetes and/or celiac disease.

Type 1 diabetes (T1D) and celiac disease (CeD) are common autoimmune diseases in children where the pathophysiology is not fully characterized. The autoimmune process involves a complex scenario of both inflammatory and regulatory features. Galectin-1 (GAL-1) has a wide range of biological activities e.g. interaction with immune cells. We examined the relationship between GAL-1 and soluble immune markers and T-cell subsets in a cohort of children with T1D and/or CeD relative to healthy children. GAL-1, together with several soluble immune markers [e.g. interleukins (IL)], tumor necrosis factor (TNF), acute phase proteins, and matrix metalloproteinases (MMP) were measured in sera from children with T1D and/or CeD by fluorochrome (Luminex) technique using children without these diseases as a reference. Subgroups of T cells, including T-regulatory (Treg) cells, were analysed by flow cytometry. Association between GAL-1, pro-inflammatory markers, and Treg cells differed depending on which illness combination was present. In children with both T1D and CeD, GAL-1 correlated positively with pro-inflammatory markers (IL-1β, IL-6, and TNF-α). Composite scores increased the strength of correlation between GAL-1 and pro-inflammatory markers, Th1-associated interferon (IFN)-γ, and T1D-associated visfatin. Contrary, in children diagnosed with exclusively T1D, GAL-1 was positively correlated to CD25hi and CD25hiCD101+ Treg cells. For children with only CeD, no association between GAL-1 and other immune markers was observed. In conclusion, the association observed between GAL-1, soluble immune markers, and Treg cells may indicate a role for GAL-1 in the pathophysiology of T1D and, to some extent, also in CeD.

Content of myeloid-derived suppressor cells in autoimmune diseases in children

Myeloid-derived suppressor cells (MDSCs) play an important role in regulation of immune response. An increase in their number in adult patients with autoimmune diseases has been reported. G-MDSCs, M-MDSCs, and MDSCs(M-G-) at different stages of autoimmune disease may both activate T cell proliferation, leading to disease progression, or inhibit it, thus promoting Treg differentiation. Arginase-1 (Arg- 1) is an enzyme in MDSCs that reduces the concentration of arginine required for T lymphocyte proliferation. Our aim was to evaluate the content of MDSCs populations and functional activity of MDSCs in children with autoimmune diseases. 75 children with inflammatory bowel diseases (IBD), 60 children with multiple sclerosis (MS), 69 children with psoriasis (PS), 62 healthy age-matched children were included into the study. The content of MDSCs ((CD3, CD19, CD56, HLA-DR)-, CD11b+ and CD33+), subpopulations of MDSCs (M-MDSCs, G-MDSCs expressing CD14 and CD15), assessment of Arg-1 activity were performed by flow cytometry techniques. The content of MDSCs in patients with IBD, MS and PS was significantly higher than in the comparison group and depended on the state of exacerbation/remission. In exacerbation and remission of IBD, MS and PS, a significant increase of MDSCs was revealed when compared with healthy children; the highest values were found in children in exacerbation of MS (Me-3.5 (2.5-5.6) % MNC against Me-1.6 (0.9-2.5) % MNC, p 0.001). In patients with MS, the content of G-MDSC, M-MDSC was significantly higher, and MDSC(M-G-) was lower than in healthy children. An increase in absolute amounts of G-MDSCs was shown in MS exacerbation compared to the disease remission state (p = 0.022). For patients with IBD, a significant increase in percentage of MDSCs and M-MDSCs (p = 0.014 and p = 0.045, respectively) was obtained in exacerbation of the disease relative to remission state. In patients with IBD, MS, and PS, a significant increase in Arg-1 activity in MDSCs was found, with a decreased number of MDSCs in patients in remission compared to exacerbation phase of the disease. In children with autoimmune diseases, an increase in the MDSC populations was found. The activity of arginase-1 in MDSCs is increased in remission, along with a decrease in their numbers.

E34 Coexisting sickle cell disease and autoimmune diseases among Nigerian children

Abstract Introduction Patients with sickle cell disease (SCD) do have a defective activation of the alternate complement pathway which increases their risk of having infections. This is thought to predispose to autoimmune disease (AID) in them. However, there is paucity of data on coexisting AID and SCD in children which may be due to under diagnosis as a result of overlapping symptoms of the two disease conditions. Objectives To highlight the clinical features, diagnostic challenge and importance of early recognition and treatment of autoimmune diseases in children with sickle cell disease. Methods Retrospective review of records of four children with sickle cell disease who were diagnosed with autoimmune diseases at the paediatric Rheumatology Clinic of Lagos State University Teaching Hospital (LASUTH) between May 2018 to February 2023. Results Case 1 15 –year –old girl known haemoglobin SC patient of haematology unit who was referred to rheumatology unit with history of worsening jaundice, abdominal swelling, headache, constitutional symptoms, left knee pain, and two episodes of blood transfusion within two months. Initally being managed for hyperhaemolytic and vaso-occlusive crisis but later referred to rheumatology unit on suspicion of autoimmune disease due to recurrent anaemia, and five episodes of blood transfusion within two months. ESR was 65 mm/h, ANA of 1:2560, positive anti-smith antibodies, elevated urine protein creatinine ratio (UPCR), low C3 and C4 and positive direct coomb’s test. Diagnosis was juvenile systemic lupus erythematosus (JSLE). She had pulse methylprednisolone, oral prednisolone, hydroxychloroquine and mycophenolate mofetil. She has improved clinically and being followed up in clinic. Case 2 10-year-old girl, known sickle cell anaemia patient who had unproductive cough of one-month duration and chest radiograph findings of bronchiectatic and fibrotic changes in the right upper/middle lobes with reduction in lung volume. Gene xpert was negative for tuberculosis but chest CT showed honeycombing in the right upper lobe implying Interstitial lung disease. Further investigations showed ESR of 5, ANA of 1:1280, borderline anti-dsDNA, positive anti-SM/RNP, normal urinalysis, normal renal function and restrictive lung disease on spirometry. She is being managed as a case connective tissue disorder with associated Interstitial Lung Disease. She is presently on mycophenolate mofetil and being followed up in clinic. Case 3 11-year-old female living with sickle cell anaemia who presented with inflammatory arthritis of the small joints of the hands, elbows and knees of nine-month duration, sclerodactyly, contractures of the PIP of the fingers, narrowing of oral aperture, generalized hypopigmented macules and abnormal nailfold capillaroscopy. ANA was 1:640, positive anti-Scl 70, negative anti-centromere, ESR of 130 mm/h, thrombocytosis, severe restriction on spirometry and features of interstitial lung disease on HRCT of the chest. She commenced mycophenolate mofetil, prednisolone and nifedipine. She later had 2 doses of rituximab due to slow clinical improvement and is being followed up. Case 4 13-year-old female with sickle cell anaemia who presented with recurrent fever & severe haemolytic anaemia requiring frequent blood transfusions (13 pints of blood over 6 months!!!). Initial diagnosis was septicaemia, and autoimmune haemolytic anaemia. Following rheumatology review, ANA was 1:640, positive anti-DsDNA, negative anti-Smith antibodies, ESR of > 150mm/h, elevated UPCR and pancytopaenia. She was later diagnosed with Lupus nephritis. She had Mycophenolate mofetil, prednisolone and hydroxychloroquine. She died of acute lupus flare 4 weeks after discharge from the hospital. Conclusions Physicians should have high index of suspicion for possible association of sickle-cell disease and autoimmune diseases so as not to delay definitive diagnosis and initiation of appropriate treatment.

Rotavirus-Associated Hospitalization in Children With Subsequent Autoimmune Disease

Rotavirus infection is a common cause of gastroenteritis in children that can trigger autoimmune processes, but the nature of this interaction remains poorly understood. To estimate the association of rotavirus infection with the risk of subsequent autoimmune disease. This population-matched cohort study used data from children and adolescents (aged younger than 18 years) in South Korea (national registers from January 1, 2002, to December 31, 2017). The cohort consisted of 86 157 patients in the exposure group who had experienced rotavirus-associated hospitalization and the same number of matched patients in the unexposed group. Data analyses were from May 1, 2020, through October 20, 2022. Hospitalization for rotavirus infection. The main outcome was childhood autoimmune diseases during the study defined by diagnoses according to the National Health Insurance Database. Hazard ratios (HRs) with 95% CIs for autoimmune diseases were estimated using a Cox model, with multiple confounding factors controlled. This cohort study consisted of 1 914 461 individuals born in South Korea from 2002 to 2005 who were potentially eligible. After exclusions, there were 86 517 individuals in the exposed group and 86 517 in the unexposed group after 1:1 incidence density sampling. The study included 49 072 (57.0%) male patients. The median (IQR) age at diagnosis of rotavirus-associated hospitalization was 1.5 (0.9-2.7) years, and the HR for autoimmune disease in the exposed group was 1.24 (95% CI, 1.19-1.28) for a mean (SD) follow-up time of 12.1 (3.2) years. The use of more stringent definitions for exposure and outcomes in a multivariable stratified analysis also indicated that rotavirus-associated hospitalization was associated with an increased risk of subsequent autoimmune disease (HR, 1.22 [95% CI, 1.16-1.28]). Sensitivity analysis showed that individuals with rotavirus-associated hospitalization was related to multiple autoimmune syndromes (2 or more: HR, 1. 51 [95% CI, 1. 31-1. 73]; 3 or more: HR, 1. 79 [95% CI, 1.18-2.72]) and that the number of rotavirus-associated hospitalization were associated with higher risks for autoimmune disease in a dose-dependent manner (single hospitalization event: HR, 1.20 [95% CI, 1.16-1.24]; multiple events HR, 1.60 [95% CI, 1.49-1.72]). Our results indicate that rotavirus-associated hospitalization is significantly associated with subsequent autoimmune disease during childhood. Clinicians should be aware of the heightened susceptibility to autoimmune disease in individuals with prior rotavirus-associated hospitalization.

Currently recommended skin scores correlate highly in the assessment of patients with Juvenile Dermatomyositis (JDM)

BackgroundJuvenile Dermatomyositis (JDM) is a rare, chronic, and life-threatening childhood autoimmune disease. Currently, there are recommended, reliable and validated measurement tools for assessment of skin disease activity in JDM including the Disease Activity Score (skinDAS), Cutaneous Assessment Tool (CAT), and the Cutaneous Dermatomyositis Disease Area and Severity Index (CDASI). The Physician’s global assessment skin visual analog scale (Skin VAS) is also widely used for skin activity in JDM. For the purpose of comparative international studies, we wanted to compare these tools to the Physician’s skin VAS (as a standard) to identify which performs better.ObjectivesWe sought to compare the correlations of these scoring tools, and separately assess the responsiveness each tool demonstrates following patient treatment, in order to see if one tool may be preferred. This was determined by assessing how well these tools correlate with each other, and the Physician’s skin VAS over time, as well as the responsiveness of each tool after patient treatment.MethodsSkin scores were recorded at a baseline (first visit after June 1st, 2018) and all follow-up office visits at the Juvenile Dermatomyositis Clinic. Following baseline visits, patients were followed up as clinically indicated. A subset of newly diagnosed patients (inception cohort) was identified. Correlations were assessed at the baseline visit and over time for the whole cohort. The correlations over time were derived using Generalized Estimating Equations (GEEs). Standardized response means with 95% confidence intervals were calculated to test score responsiveness for the nested inception cohort.ResultsThe skinDAS, CAT and CDASI all correlated highly with each other and with the Physician’s skin VAS. The three scoring tools accurately reflected Physician’s skin VAS scores over time. In addition, all tools showed moderate to high responsiveness following treatment.ConclusionAll studied skin score tools performed well in our study and appear to be useful. Since no tool far outperforms the others, arbitrary consensus will be needed to select a single standard measurement tool for the purposes of efficiency and global comparability.

Paediatric autoimmune diseases with ELANE mutations associated with neutropenia

ObjectiveTo explore the clinical characteristics of autoimmune diseases in children with ELANE mutations.MethodsThree cases of children with ELANE mutations manifesting as autoimmune diseases, who were under treatment from April 2020 to May 2021, were retrospectively analysed.ResultsAmong the three children, two were boys aged 15 years and 22 months (cases 1 and 3) respectively, and the other one was a 22-month-old girl (case 2). All the cases had recurrent infections. Case 1 presented with cyclic neutropenia and systemic lupus erythematosus (SLE). Case 2 presented with severe neutropenia and autoimmune haemolytic anaemia (AHIA). Case 3 presented with severe neutropenia and anti-neutrophil cytoplasm antibodies (ANCA)-associated small vasculitis. Genetic tests showed that they all had heterozygous mutations in the ELANE gene. Case 1 was treated with methylprednisolone and hydroxychloroquine sulphate for 2 years, making neutrophil level return to normal. Case 2 received allogeneic hematopoietic stem cell transplantation and has stopped taking antibiotics, steroids and all the immunosuppressors. Case 3 received subcutaneous injections of granulocyte colony-stimulating factor, oral prednisone and cyclophosphamide. The boy in case 3 has been followed up for one year, and his absolute neutrophil count has increased to 1.56 × 109/L.ConclusionPatients with ELANE mutations, combined with autoimmune diseases, may have recurrent infections. Disease-modifying antirheumatic drugs (DMARDs) are effective for autoimmune diseases. Autoimmune diseases with ELANE mutations associated with neutropenia can be cured through allogeneic hematopoietic stem cell transplantation.

Antinuclear antibodies in children: indirect immunofluorescence patterns, antigen targets and associated diagnoses

Antinuclear antibodies tests are of a paramount importance in the diagnosis, classification, prognostic evaluation and management of autoimmune diseases in children. The present study aimed to describe the immuno-clinical profile of antinuclear antibodies tests in a pediatric population in order to guide the clinical practice of biologists and clinicians. Our study enrolled 268 children. Antinuclear antibodies screening was performed using the indirect immunofluorescence assay on HEp-2 cells. Identification of target antigens was conducted using separately or at one timepoint the following techniques: enzyme-linked immunosorbent assay, Immunodot and Chemiluminescence. The average age of patients was 9.6 ± 4.3 years, with a female predominance (sex-ratio = 1.9). Antinuclear antibodies screening was positive in 40.67% of cases. The most frequently observed antinuclear antibodies patterns were speckled (52.3%), homogeneous (13.8%) and mixed homogeneous-speckled (13.8%). Autoantibodies were detected in 4 patients (2.51%) for whom ANA testing using the indirect immunofluorescence assay was negative. Positive antinuclear antibodies specificities were detected in connective tissue diseases (44.03%; n = 48), organ-specific autoimmune diseases (10.09%; n = 11), and in non-autoimmune conditions (inflammatory diseases, infections, hematological diseases, vasculitis and Wilson’s disease) (32.08%; n = 35). Our study revealed a high rate of positive antinuclear antibodies tests in the pediatric population, mainly related to autoimmune diseases (54.12%) besides non-autoimmune conditions (32.08%). Therefore, screening and interpretation of antinuclear antibodies testing in children require the consideration of clinical data and a close collaboration between clinicians and biologists.

Construction of molecular subgroups in childhood systemic lupus erythematosus using bioinformatics

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder. In patients with childhood SLE (cSLE), the onset of the disease occurs before 18 years of age and accounts for a high proportion of childhood autoimmune diseases. Adult SLE and cSLE differ in terms of clinical manifestations, gene expression profiles, and treatment. Because current diagnostic methods do not meet clinical requirements, researchers currently use transcriptome analysis to investigate the characteristics of the cSLE genome. In the present study, we used bioinformatics methods to genotype cSLE and identify potential therapeutic targets. The transcriptomes of 952 patients with cSLE and 94 normal controls were obtained from the Gene Expression Omnibus using unsupervised class learning to determine the genotypes in the microarray dataset, and the clinical characteristics, differentially expressed genes, and biological characteristics of the subtypes were analyzed. Patients with cSLE were accordingly classified into three subgroups. Subgroup I was associated with lupus nephritis, female patients, and a high SLE disease activity index, and the disease in this subgroup was more severe than that in other subgroups. The SLE disease activity index in subgroup II was low; this subgroup may be related to lupus vasculitis. Subgroup III mostly included male patients and was associated with neuropsychiatric manifestations of lupus. We divided patients with cSLE into three subgroups with different characteristics based on transcriptome data. Our findings provide molecular evidence for future diagnosis and individualized treatment of cSLE.

PADI4 and IL-33 gene polymorphisms associated with differential susceptibility to juvenile-onset systemic lupus erythematosus and juvenile idiopathic arthritis in Chinese children

Juvenile systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA) are two common types of autoimmune diseases in children with unclear pathogenesis. Both peptidyl arginine deiminase type IV (PADI4) and interleukin 33 (IL-33) are the key molecular involved in immune responses in autoimmune diseases. Usually, it may share the same risk genetic alleles for autoimmune diseases. So measurement of PADI4 and IL-33 polymorphisms was conducted with 303 healthy controls, 144 JSLE patients and 160 JIA patients in this study. It demonstrated that there was a significant association between PADI4 genotypes (rs2240340: CT, CT + CC), IL-33 genotype (rs1929992: TT) and JSLE susceptibility in Southwest China population. While no significant association with the risk of JIA were observed no matter at allelic or genotypic levels. Our study reveals the importance of PADI4 and IL-33 polymorphisms with JSLE risk and their roles in the development of the diseases need more further researches.

Immune Thrombocytopenia Purpura in Children in Lebanon: Prevalence, Treatment Modalities, and Clinical Outcomes in a Retrospective Study

Background: Immune thrombocytopenia purpura (ITP) is one of the most common autoimmune diseases in children characterized by a decreased number of circulating platelets combined with impaired platelet production. There is limited literature data on the prevalence and treatment modalities, and outcome of ITP in children from Lebanon. Methods: We retrospectively reviewed the demographic and clinical data of 59 patients aged 0–18 years diagnosed with ITP between January 2007 and April 2016 in different hospitals in Beirut and the south of Lebanon. Results: ITP patients represented 2.5% of the total number of children admitted to these hospitals during this period. Among the ITP children, 55.93% were male and 44.07% were female. The greatest number of ITP children were in the 1–4 year group, followed by the 5–9 year group. As for the clinical course of the disease, 40.68% of the ITP children presented acute ITP, whereas 59.32% presented chronic ITP. Among the different therapeutic approaches adopted to treat these ITP children, intravenous immunoglobulin was the most commonly used, followed by steroids, a combination of these both agents, cyclosporine, and splenectomy. Interestingly, these therapeutic modalities induced a statistically significant increase in the patients’ platelet count. In addition, the clinical course of ITP was not significantly associated with each of the age group, the platelet count at diagnosis, and gender of patients. Conclusion:This study showed the prevalence of ITP among children from Lebanon, where more than half of ITP children presented a chronic disease. Further studies are needed to evaluate additional predictors of chronic ITP among children from Lebanon and help medical providers make informed decisions about treating childhood ITP. Doi: 10.28991/SciMedJ-2022-04-04-02 Full Text: PDF

Transitions from pediatric to adult rheumatology care for juvenile idiopathic arthritis: a patient led qualitative study

BackgroundJuvenile idiopathic arthritis (JIA) is a childhood autoimmune disease that causes swelling and pain in at least one joint. Young people with JIA experience symptoms that persist into adulthood, and thus will undergo a transition including the o transfer of care from a pediatric rheumatologist an adult rheumatologist. Missing from the literature is research that centres the transition experience of young people with JIA in Canada. This goal of this patient-led research was to explore the experience young people with JIA through the process of transition.MethodsQualitative study using the Patient and Community Engaged Research (PaCER) approach. Trained patient-researchers conducted three focus groups using the Set, Collect and Reflect PaCER process. Participants, recruited via purposive and snowball sampling using research/personal networks and social media, were young people with JIA in Canada between 18 and 28 years who had experienced with the process of transition to adult care. Recordings were transcribed verbatim. Patient researchers individually coded overlapping sections of the data, and thematic analysis was conducted.ResultsIn total, nine individuals participated in one or more focus groups. Three themes were identified, with sub-themes: preparedness for transition (readiness for the transfer of care, developing self-advocacy skills), continuity and breadth of care (changing relationships, culture shock, new responsibilities), need for support (social support, mental health support, and ongoing support needs – beyond the transfer of care. Peer support was a connecting concept in the support sub-themes. Transition was more than a change in primary physician but also a change in the care model and breadth of care provided, which was challenging for young people especially if they had insufficient information.ConclusionsTransition from pediatric to adult care in rheumatology is a significant period for young people living with JIA, and this patient-led study provided insight into the experience from the perspective of young people with JIA which is critical to informing the development of supports for patients through the process. Patients, caregivers, pediatric and adult rheumatologists and members of the multi-disciplinary care team need to collaborate in terms of resources preparing for transfer, and support throughout the transition process to ensure a successful transition process.

A Co-diagnosis of Crohn Disease and Autoimmune Diabetes in an Adolescent Patient.

Inflammatory bowel disease (IBD) is a lifelong, immune-mediated disorder that often occurs in childhood and is becoming increasingly common worldwide. Diagnosis of IBD in children remains difficult due to the spectrum of symptoms, including gastrointestinal and extraintestinal manifestations. Type 1 diabetes mellitus (T1D) is one of the most common autoimmune diseases in children and adolescents. Classic manifestations of T1D in young people include polyuria, polydipsia, abdominal pain, weight loss, and ketoacidosis. However, children with autoimmunity of pancreatic β-cells may remain euglycemic and asymptomatic for many years. An accurate and prompt diagnosis of IBD and T1D is particularly important in children because they can negatively affect growth, psychosocial function and overall well-being. We present a case in which a previously healthy child was co-diagnosed with Crohn disease and T1D during a routine pediatric evaluation in the outpatient clinic of a peripheral secondary hospital.