Childhood-onset Systemic Lupus Erythematous Research Articles

Contribution of genetic variants associated with primary immunodeficiencies to childhood-onset systemic lupus erythematous

A dysregulated immune response is a hallmark of autoimmune disorders. Evidence suggests that systemic autoimmune diseases and primary immunodeficiency disorders (PID) may be similar diseases with different clinical phenotypes. This study aimed to investigate the burden of PID-associated genetic variants in patients with childhood-onset systemic lupus erythematosus (cSLE). We enrolled 118 cSLE patients regularly followed at Chang Gung Memorial Hospital. Targeted next-generation sequencing identified PID genetic variants in patients versus 1,475 unrelated healthy individuals that were further filtered by allelic frequency and various functional scores. Customized immune assays tested the functions of the identified variants. Upon filtration, 36 (30.5%) patients harbored rare variants in PID-associated genes predicted to be damaging. One homozygous TREX1 (c.294dupA) mutation and four heterozygous variants with possible dominant PID traits, including BCL11B (c.G1040T), NFKB1 (c.T695G), and NFKB2 (c.G1210A, c.G1651A), were discovered. With recessive traits, variants were found across all PID types; one-fifth involved phagocyte number or function defects. Predicted pathogenic PID variants were more predominant in those with a family history of lupus regardless of infection susceptibility. Moreover, mutational loads were greater among cSLE patients than controls despite sex or age at disease onset. While greater mutational loads were observed among cSLE patients with peri-pubertal disease onset, no significant difference in sex or phenotype were noted among cSLE patients. Our findings suggest that cSLE is mostly not monogenic. Gene-specific analysis and mutational load investigations suggested that rare and predicted damaging variants in PID-related genes potentially contribute to cSLE susceptibility.

Serum levels and significance of soluble B-cell maturation antigen in childhood-onset systemic lupus erythematosus with renal involvement.

The aim of this study was to investigate serum levels of soluble B-cell maturation antigen (sBCMA) in childhood-onset systemic lupus erythematous (cSLE) patients with renal involvement, and to elucidate their association with clinical characteristics. 116 cases of cSLE patients with renal involvement (84 females and 32 males; median age 11.6 (10.1, 12.9) years) hospitalized in Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital, Sun Yat-sen University and 31 healthy controls (HCs) were enrolled. Serum concentrations of sBCMA were determined using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory information of cSLE patients were retrospectively analyzed. Serum sBCMA levels were significantly increased in primary cSLE when compared with treated cSLE patients and HCs, whereas there was no significant difference between treated cSLE patients and HCs. Patients with high disease activity displayed higher serum sBCMA levels compared with those with no or mild to moderate disease activity. Positive correlation was observed between serum sBCMA levels and systemic lupus erythematosus disease activity index-2K (SLEDAI-2K), antinuclear antibody titers, anti-double-stranded DNA titers, erythrocyte sedimentation rate, and immunoglobulin G levels, while sBCMA levels were negatively correlated with blood white blood cell count, hemoglobin, platelet count, complement C3 and C4 levels. Serum sBCMA levels decreased as disease ameliorated after treatments among 11 cases with follow-up examinations. In cSLE patients with renal involvement, serum sBCMA levels correlated significantly with disease activity, immunological, and hematological parameters, but not with renal parameters. Our results suggest the potential and significance of serum sBCMA as a biomarker in cSLE patients.

Raynaud's phenomenon in childhood-onset systemic lupus erythematous.

1. Aringer M, Costenbader K, Daikh D, . 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. Arthritis Rheumatol 2019; 71: 1400-12. Google Scholar

Adherence to medication by adolescents and young adults with childhood-onset systemic lupus erythematosus.

Background: Approximately 20% of all cases systemic lupus erythematous (SLE) are juvenile onset. Children and adolescents with SLE usually present with more severe illness and have a higher mortality rate compared to adults with SLE. Adherence to medications in children and adolescents has a major impact on disease control as well as short- and long-term outcomes. Improved understanding of adherence rates, risk factors for non-adherence, and barriers to adherence are essential in order to increase patient adherence with medication regimens. The aim of our study was to evaluate adherence to medications among children and young adults with pediatric-onset SLE and identify barriers for non-adherence by utilizing several adherence evaluation methods.Methods: Adherence to medications of patients aged 12-25, with childhood-onset SLE was assessed as follows: (1). The brief medication questionnaire (BMQ): self-report tool for screening adherence and barriers to adherence. (2). Mycophenolic acid (MPA) serum level. (3). Medication possession ratio (MPR): data assessing 90-day refills and dispense prior to patient's enrollment was collected.Results: Of the 38 patients who were enrolled in the study, 65% were found to be non-adherent according to at least 1 measurement method. Forty-four percent of patients were found to be non-adherent based on the self-reported questionnaire (BMQ). Of those taking MMF, 33% had an MPA level < 1mcg/mL and were defined as non-adherent. Seventeen percent of patients were found to be non-adherent according to pharmacy refills rate. Forty-six percent of patients stated that their medications caused side effects, 33% of patients indicated difficulty remembering to take the medications, and 25% reported difficulty paying for medications. The disease activity index (SLEDAI) score of the "adherent group" at diagnosis was significantly lower compared to the "non-adherent" group. Patients with private insurance had more access barriers to obtaining medications compared to patients with public insurance.Conclusion: Non-adherence to medications is highly prevalent among cSLE patients. Higher SLEDAI score is a risk factor for non-adherence. Adherence to medications should be routinely evaluated among adolescence and young adults with cSLE and barriers to adherence need to be addressed to decrease morbidity and improve patient outcomes.

Autoantibody Profile of Childhood Onset Systemic Lupus Erythematosus: An Audit of Immunopathology Laboratory of a Tertiary Care Centre

ntroduction: Systemic Lupus Erythematous (SLE) is an autoimmune disease, which commonly affects females and is associated with formation of various Antinuclear Antibodies (ANA). Childhood onset SLE has some similarities and differences in immunological profile and clinical manifestations from adult onset SLE patients. Aim: To study the spectrum of clinical manifestation and autoantibody profile of childhood onset SLE patients and to compare with adult SLE patients. Materials and Methods: The present study was a retrospective observational study in which 74 patients of childhood onset SLE and 91 patients of adult SLE were included. The study was conducted from October 2017 to March 2021 in Department of Immunopathology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. Detailed clinical and laboratory data were collected from medical records. Serum ANA and anti-dsDNA (Deoxyribonucleic Acid) detection was done by solid phase enzyme immunoassay methods. Antibodies to extractable nuclear antigen were detected by dot blot immunoassay. Chi-square test (International Business Machines (IBM) Statistical Package for the Social Sciences (SPSS) version 21.0) was used to compare categorical data of childhood onset SLE and adult SLE patient groups. Results: The mean age of childhood onset SLE patients was 13.05±4.26 years with female: male ratio of 3.93:1. Malar rash (p=0.001) and renal involvement (p=0.021) was significantly more frequent in childhood onset SLE but oral ulcer was significantly more frequent (p=0.038) in adult patients. Anti-ds DNA positivity and reduction in complements C3 and C4 were more commonly seen in childhood onset SLE patients. Conclusion: Age is an important influence on clinical manifestations and autoantibody profile of SLE. Childhood onset SLE showed more frequent renal and skin involvement and more significant activity measured by reduction of complements. Awareness of the same will help our clinicians to detect renal involvement at an early stage and develop organ specific management protocol.

Effect of Hypertension on Childhood-onset Systemic Lupus Erythematous in a Tertiary Medical Center in Korea

This corrects the article "Effect of Hypertension on Childhood-onset Systemic Lupus Erythematous in a Tertiary Medical Center in Korea" in Volume 24 on page 107.

Effect of Hypertension on Childhood-onset Systemic Lupus Erythematous in a Tertiary Medical Center in Korea

Effect of Hypertension on Childhood-onset Systemic Lupus Erythematous in a Tertiary Medical Center in Korea

Effect of Hypertension on Childhood-Onset Systemic Lupus Erythematous in a Tertiary Medical Center in Korea

Effect of Hypertension on Childhood-Onset Systemic Lupus Erythematous in a Tertiary Medical Center in Korea

Simultaneous Pancreatitis and Myocarditis in Childhood-Onset Systemic Lupus Erythematous.

Simultaneous Pancreatitis and Myocarditis in Childhood-Onset Systemic Lupus Erythematous.

Blood pressure control over time in childhood-onset systemic lupus erythematous.

Introduction Hypertension (HTN) is prevalent in patients with systemic lupus erythematosus (SLE) and causes early cardiovascular aging and progression of renal and cardiac disease. The aim of this longitudinal retrospective study was to evaluate the prevalence of HTN, the follow-up blood pressure trends, and risk factors for HTN in a population-based cohort with childhood-onset SLE (cSLE). Methods Demographic and clinical data of consecutive visits from the baseline to the last visit were extracted from electronic medical records of patients with cSLE. Results A total of 110 patients with cSLE were identified with a median follow-up duration of 29.5 months; 19% had lupus nephritis (LN) at diagnosis. Further, 29% and 23% had HTN and preHTN at the baseline visit. Compared to those without HTN, patients with HTN had higher disease activity, obesity, more frequent LN, and lower eGFR. In multivariate analysis, the presence of LN, obesity, and high extra-renal disease activity were independent predictors of HTN at baseline. Conclusions While HTN is a known feature of LN, HTN is common and persistent in cSLE without LN, with about one-third of patients having uncontrolled elevated blood pressure almost three years after the onset of lupus. In addition to LN, obesity and high overall disease activity were independent predictors of HTN.

Description of Malignancy Rates in Childhood- and Adult-Onset Systemic Lupus Erythematous by Proportional Meta-analysis

Describe malignancy rates in childhood onset and adult onset systemic lupus erythematous (SLE) by proportional meta-analysis. Two reviewers screened data from PubMed (1966-2015), EMBASE (1980-2015), and LILACS (1982-2015) for SLE-associated malignancy. Proportional meta-analysis with a random-effects model and 95% confidence intervals (CIs) were calculated according to SLE onset age and mean follow-up time. Statistical difference was defined by 95% CI overlap. Overall the malignancy rate reported in 30 case series with 96,578 subjects was 3.4% (95% CI, 0.0260-0.0442; I = 97.6%; P < 0.0001). The malignancy rate was 4.2% (95% CI, 0.0318-0.0531; I = 98%; P < 0.0001) in 25 adult-onset SLE series, compared with 0.5% (95% CI, 0.0003-0.0154; I = 62.6%; P = 0.03) in 5 childhood-onset SLE series. Overall, in those with less than 5 years' follow-up, the malignancy rate was 2.8% (95% CI, 0.013-0.047; I = 91%; P < 0.0001) compared with 3.6% (95% CI, 0.0226-0.0531; I = 98.3%; P < 0.0001) in those with more than 5 years' follow-up, which was not significant, with 95% CI overlap. The meta-analysis indicated lower malignancy rates in pediatric-onset SLE compared with adult-onset SLE, but accrued data from childhood-onset SLE are still needed.

Developing consensus treatment plans for proliferative lupus nephritis in childhood-onset systemic lupus erythematous

Purpose The SLE Subcommittee of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) is developing standardized treatment plans for proliferative lupus nephritis (LN) in childhood-onset SLE (cSLE) which will serve as the basis for future comparative effectiveness studies. The Initial Delphi survey revealed wide variability in the treatment of LN in cSLE. This abstract decribes the process of developing standardized evidence-based induction treatment plans for LN in cSLE by using consensus methods.