Juvenile-onset Systemic Lupus Erythematosus Research Articles

P154 Male lupus characteristics from multi-ethnic cohort

Abstract Background/Aims Systemic lupus erythematous (SLE) is a chronic autoimmune (AI) disease of unknown etiology. It predominantly presents in women and only 1 in 10 of sufferers are men. We sought to examine the clinical pattern in male lupus patients in a tertiary multi-ethnic lupus centre in East London, UK. Methods Male lupus patients were identified through review of a pre-existing lupus patients database and clinic lists at Barts Trust. All patients’ electronic notes were reviewed prior to a telephone interview. All the participants fulfilled the ACR 1997 criteria for SLE. Descriptive data analysis was performed for all identified patients. Results Fifty-one patients were identified. Sample demographics showed that male lupus was more prevalent among Afro-Caribbeans (37%,n=19), followed by Asians (33%,n=17) and Caucasians (29%,n=15). The median age was 40.5 (IQR:32.5-52.7) years, with median age at SLE diagnosis 28 years (IQR:23-45).Family history of an AI condition was seen in 25%, whilst 14% had a family history specifically of SLE. Possible significant stressor prior to diagnosis reported in 45% (n = 23) patients. Serological evidence of previous infection with EBV, VZV or parvovirus was found in 76%. Although all patients were below the state pension age of 66, more than half were unemployed. The majority of males had multiorgan involvement including renal (67%,n=34), cutaneous (55%,n=28), hematological (45%,n=23), musculoskeletal (31%,n=16), cardiac (27%,n=14), pulmonary (20%,n=10), and neurologic (14%,n=7). Renal biopsy was done in 33/34 renal cases and the showed proliferative class-III/IV in 65%. Hypertension was a significant comorbidity in 39%, 47% had a concomitant AI condition. Juvenile-onset SLE was diagnosed in 6% of the patients with median age at disease onset 10 years (IQR:14-16,100% Caucasians). These males all had kidney nephropathy class-IV/V. Regarding serology, 94% were positive for antinuclear antibody, 40% speckled, 31% homogenous, and 8% for nucleolar and mixed pattern. Two patients ANA test was not recorded but they had confirmed renal/cutaneous biopsy findings.Three-quarters were positive for anti-double stranded DNA. Ro and La antigens were detected in 35% and 8%, while anti-Sm and anti-RNP antibodies were detected in 37% and 43%, respectively. Antiphospholipid antibodies were identified in less than a third, of which 40% presented with thrombotic events. Triple antiphospholipid antibodies was detected in 53%, 20% had LA, 15% had aCL, and 7% had either anti-B2GP1 or aCL/anti-B2GP. Conclusion Our dataset demonstrates a higher prevalence in Afro-Caribbean and Asians and a young age of onset (median 28 years) with presentation about 10 years earlier than most other reports. The majority were unemployed and reported significant life-stressors. Over three-quarters of patients had evidence of prior infection.Most of the lupus males had multiorgan involvement and over two-thirds had renal involvement, proliferative class-III/IV. There was a high prevalence of dsDNA, ENA (anti-Ro) and APL. Disclosure H. Aldeyarbi: None. S. George: None. G. Marchan: None. R. Rajakariar: None. A. Cove-Smith: None. A. Pakozdi: None. M. Cunningham: None. M. Lewis: None. B. Turner: None. D. Pyne: None.

P094 Comprehensive comparison of juvenile-onset systemic lupus erythematosus guidelines for diagnosis and management to those used in adult-onset disease

Abstract Background/Aims Juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune disorder that causes multisystem damage. Paucity of data limits the evidence upon which to base recommendations for diagnosis, monitoring, and management of JSLE. JSLE patients often present more acutely, with more severe complications and greater need for corticosteroids and disease-modifying therapies earlier in life when compared to those with adult-onset SLE (aSLE). The SHARE initiative generated a set of guidelines to standardise JSLE care across Europe. This aim was to undertake a comprehensive comparison aimed at comparing the SHARE guidelines to those developed by the BSR (for aSLE) to identify similarities, differences, and areas in which more research was needed. Methods The SHARE evidence-based, consensus-derived recommendations were established by a European wide panel of paediatric rheumatologists according to EULAR standard operating procedures using a systematic literature search with strict inclusion criteria. Adult-derived evidence was included when lack of paediatric literature existed but reviewed to adapt adult guidelines to be more suitable for paediatric use. The BSR guidelines built upon existing EULAR guidelines, selecting specific recommendations by prioritisation. Both SHARE and BSR used the same method of validating guidelines using Level of Evidence, grade of recommendation and strength of agreement by the panel (SOA) to support their recommendations. A systematic comparison was performed by identifying specific subgroups of recommendations related to: diagnosis, background, neuropsychiatric and monitoring and management guidelines. These subgroups were then compared by assessing the number of guidelines related to each group and the average SOA for each. A detailed comparison into the specific guidelines was then performed to provide in depth analysis of the similarities and differences between the groups and identify areas missing and where more work was needed. Results There are many similarities between the two sets of recommendations. Although some of these are a result of the manifestations being the same in adults and children, a significant proportion of these similarities were due to the lack of background data to base recommendations on for JSLE. Therefore, adult-derived guidelines, particularly the EULAR guidelines have been used which were also used as background for BSR recommendations. A key difference was the lack of recommendations regarding neuropsychiatric manifestations (NP-aSLE) in adult-onset disease. A detailed comparison between individual guidelines has been generated and potential reasons for the discrepancies between the guidelines identified. Conclusion The results demonstrate the need for significantly more research to inform generation of more specific JSLE guidelines, particularly in management of the disease manifestations specific to children. Many similarities between these adult and paediatric guidelines underline the importance of generating common guidelines where possible for JSLE and aSLE. More work is needed in NP-aSLE to produce more balanced generalised results. Disclosure T.E. Kelly: None. M.W. Beresford: None.

Systemic lupus erythematosus with juvenile onset: current status of the problem (literature review)

Patients with juvenile-onset systemic lupus erythematosus (jSLE) account for up to 25% of all SLE patients. The main difference between jSLE and SLE in adults is the greater role of genetic factors in the pathogenesis, higher activity, earlier development of complications and the need for more aggressive immunosuppressive therapy, which allows us to consider the onset of the disease in childhood as a special phenotype of SLE. The relevance of the study of jSLE arises from the variability of clinical manifestations and the unpredictability of the course, the difficulty of early diagnosis, the rapid development of organ damage and the unfavorable life prognosis.The article presents the most important modern data on the diagnosis, classification, features of the clinical picture and treatment approaches of jSLE from a practical point of view.

Assessment of hematologic indices for diagnosis in juvenile systemic lupus erythematosus.

The aim was to present effective approaches utilizing novel hematological parameters for early diagnosis of juvenile-onset systemic lupus erythematosus (jSLE). Our study at Umraniye Training and Research Hospital involved a jSLE patient cohort from 2016 to 2022 and matched healthy controls aligning with sex and age. We use the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) for disease activity. Our approach was to analyze leukocyte, neutrophil, lymphocyte, monocyte, and platelet counts, along with ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and monocyte-to-platelet ratio (MPR). We also explored novel indices: the systemic inflammatory index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) to identify relationships between systemic indices and jSLE activity. Upon comparative analysis with the healthy control group, systemic lupus erythematosus (SLE) patients exhibited significantly elevated levels of the hematological parameters NLR, SII, and SIRI (p-values: 0.010, 0.048, 0.025, respectively). Among SLE patients, neutrophil, lymphocyte, and platelet distribution width (PDW) values were notably higher, while hemoglobin, red blood cell distribution width (RDW), and procalcitonin (PCT) values were significantly lower. In comparison, C-reactive protein (CRP) and sedimentation values were markedly elevated in the SLE group in contrast to the healthy control cohort. Patients with significantly elevated disease activity had notably higher values of NLR (p = 0.010) and SII (p = 0.048). Among patients with positive antinuclear antibodies (ANA), elevated levels of NLR, SII, and SIRI were noted (p-values: 0.018, 0.021, 0.035). In this study, the novel hematological markers SII, SIRI, and AISI were found to effectively reflect inflammation in SLE patients, exhibit associations with high disease activity, and demonstrate heightened sensitivity in detecting cases with high disease activity.

Reduced expressions of apoptosis-related proteins TRAIL, Bcl-2, and TNFR1 in NK cells of juvenile-onset systemic lupus erythematosus patients: relations with disease activity, nephritis, and neuropsychiatric involvement.

Lupus pathogenesis is mainly ascribed to increased production and/or impaired clearance of dead cell debris. Although self-reactive T and B lymphocytes are critically linked to lupus development, neutrophils, monocytes, and natural killer (NK) cells have also been implicated. This study assessed apoptosis-related protein expressions in NK cells of patients with juvenile-onset systemic lupus erythematosus (jSLE) and relations to disease activity parameters, nephritis, and neuropsychiatric involvement. Thirty-six patients with jSLE, 13 juvenile dermatomyositis (JDM) inflammatory controls, and nine healthy controls had Fas, FasL, TRAIL, TNFR1, Bcl-2, Bax, Bim, and caspase-3 expressions in NK cells (CD3-CD16+CD56+) simultaneously determined by flow cytometry. Disease activity parameters included Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score, erythrocyte sedimentation rate, C-reactive protein level, anti-double strain DNA antibody level, complement fractions C3 and C4 levels. Patients with jSLE had a profile of significantly reduced expression of TRAIL, Bcl-2, and TNFR1 proteins in NK cells when compared to healthy controls. Similar profile was observed in patients with jSLE with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. Patients with jSLE with positive anti-dsDNA also had reduced expression of Bax in NK cells when compared healthy controls and to those with negative anti-dsDNA. Yet, patients with jSLE with negative anti-dsDNA had reduced mean fluorescence intensity (MFI) of Bim in NK cells compared to healthy controls. Patients with jSLE with nephritis also had reduced MFI of Fas in NK cells when compared to those without nephritis. In addition, in patients with jSLE, the proportion of FasL-expressing NK cells directly correlated with the SLEDAI-2K score (rs = 0.6, p = 0.002) and inversely correlated with the C3 levels (rs = -0.5, p = 0.007). Moreover, patients with jSLE had increased NK cell percentage and caspase-3 protein expression in NK cells when compared to JDM controls. This study extends to NK cells an altered profile of TRAIL, Bcl-2, TNFR1, Fas, FasL, Bax, Bim, and caspase-3 proteins in patients with jSLE, particularly in those with active disease, positive anti-dsDNA, nephritis, and without neuropsychiatric involvement. This change in apoptosis-related protein expressions may contribute to the defective functions of NK cells and, consequently, to lupus development. The full clarification of the role of NK cells in jSLE pathogenesis may pave the way for new therapies like those of NK cell-based.

Mental disorders in children with rheumatic diseases

The prevalence of concomitant mental disorders in children with rheumatic diseases is notably higher than in the overall population. However, psychiatric comorbidity in pediatric rheumatology remains poorly understood, whereas approaches to mental disorders therapy in children with rheumatic diseases are not clearly defined. The review article considers currently available data on the mental disorders prevaling in patients with juvenile idiopathic arthritis, juvenile-onset systemic lupus erythematosus and juvenile primary fibromyalgia. The article provides data on the efficacy and safety studies of psychotherapy and psychopharmacotherapy. It also discusses application prospects of biological disease-modifying antirheumatic drugs for treatment of comorbid depression in children with rheumatic diseases.

Lymphocyte apoptosis and its association with the inflammatory markers and disease severity in juvenile-onset systemic lupus erythematosus patients

BackgroundThe defective clearance of apoptotic bodies in juvenile-onset systemic lupus erythematosus (jSLE) potentially leads to the persistence of autoreactive lymphocytes and the perpetuation of the autoimmune response. These factors contribute to the disturbance in lymphocyte apoptosis and show potential as key determinants in the clinical course and severity of jSLE. This study evaluates the role of peripheral blood (PB) lymphocyte apoptosis in prognosis of jSLE and as a predictor for disease activity.MethodsThe study involved 100 jSLE patients and 50 healthy controls. Flow cytometry was used to analyze percentages of lymphocyte apoptosis in PB of all study participants. Plasma levels of pro-inflammatory cytokines were determined using ELISA.ResultsOur results showed that percentages of lymphocyte apoptosis in PB of jSLE patients are significantly higher than those of healthy controls. These percentages are significantly positively associated with disease activity of patients (SLEDAI-2 K). Furthermore, plasma cytokine levels (IL-17, IFN-γ and TNF-α) are significantly elevated in jSLE patients compared to their levels in healthy controls. Also, there are weak significant positive correlations between percentages of PB lymphocyte apoptosis and each of IL-17 and IFN-γ plasma levels in jSLE patients. Moreover, PB lymphocyte apoptosis percentages among jSLE patients are higher in the presence of some clinical and laboratory features than those in their absence.ConclusionPeripheral apoptotic lymphocytes could contribute to the prognosis of jSLE and could be used as a predictor for disease activity in jSLE patients.

Abstract 13 — Comparison of Clinical and Serological Features in Juvenile and Adult-Onset Systemic Lupus Erythematosus

Background Systemic lupus erythematosus (SLE) has varying clinical and serological features in juvenile and adult-onset disease groups, depending on the ethnicity. Objectives: To compare the disease characteristics of patients with adult-onset (ASLE) and juvenile-onset systemic lupus erythematosus (JSLE). Methods It is a cross-sectional study, carried out at Rheumatology department Fauji Foundation Hospital. 184 SLE patients were included. They were divided into adult (n=152) and juvenile (n=32) group. The clinical and serological features at the time of disease onset were compared between the two groups. Statistical analysis was done using chi square and t-test. Results The mean age was 36.22 ± 11.48 in adults and 19.94 ± 7.17 in the juvenile group (t = 7.71, p<0.001). The duration of disease was 46.05 ± 45.74 months(adult) and 62.43 ± 84.00 months (juvenile). There was no significant difference in disease activity, SLE disease activity index (SLEDAI) was 13 in adult lupus patients and 14.5 in the juvenile, t-value=1.1 and p-value=0.39. Sicca symptoms were significant in the ASLE (p=0.004). Neuropsychiatric manifestations (p=0.03), thrombocytopenia (p=0.048) and low complement levels (0.02) were significantly higher in JSLE. Serological profiles did not differ significantly in the two groups. Conclusion The features of SLE differ in adult and juvenile patients. Neurological involvement and thrombocytopenia were more prevalent in JSLE, whereas sicca symptoms were more frequently found in ASLE.

Persisting mortality gap in systemic lupus erythematosus; a population-based study on juvenile- and adult-onset SLE in Norway 1999-2022.

To estimate mortality and survival rates of systemic lupus erythematosus (SLE) in a contemporary, population-based setting and assess potential influences by time, sex, ethnicity, classification criteria and age at diagnosis. We assessed mortality and survival in the Nor-SLE cohort, which includes all chart-review confirmed SLE cases resident in Southeast Norway (population 2.9 million) 1999-2017. Study end was at death, emigration, or 1 October 2022. We defined juvenile SLE by age <16 years at diagnosis. For standardized mortality rate (SMR) estimates, we applied 15 population controls per case, all matched for age, sex, residency, and ethnicity. We analyzed survival by Kaplan-Meier and risk factors by cox regression. The Nor-SLE cohort included 1558 SLE cases, of whom 749 were incident and met the 2019 European Alliance of Associations for Rheumatology and American College of Rheumatology (2019-EA) classification criteria. SMR was increased to 1.8 (95% CI 1.6-2.2) in incident adult-onset SLE but did not differ between females and males. Survival rates at 5-, 10-, 15 and 20-years were lower in incident adult-onset SLE than in matched controls. In multivariable analysis, lupus nephritis associated with decreased survival, while sex did not. Separate, long-term mortality analyses in the total Nor-SLE cohort showed that SMR peaked at 7.2 (95% CI 3.3-14) in juvenile-onset SLE (n = 93) and fell gradually by increasing age at SLE diagnosis. This study shows persistence of a mortality gap between adult-onset SLE and controls at population level and provides indications of worryingly high mortality in juvenile-onset SLE.

Musculoskeletal symptoms in juvenile onset systemic lupus erythematosus

In juvenile onset systemic lupus erythematosus (SLE), musculoskeletal involvement is one of the most common manifestations. Musculoskeletal symptoms may be due to disease activity itself, organ damage due to SLE activity, drug exposure, or comorbidities. Although they are not life-threatening, they still have a significant impact on disability severity and social exclusion. This article discusses the clinical features of various causes of musculoskeletal manifestations in SLE with onset in childhood and adolescence, the adequate interpretation of which is important for diagnosing and evaluating SLE activity and for correcting the treatment of the disease, thereby improving the long-term prognosis and quality of life of patients.

IL12B and IL17 genes polymorphisms associated with differential susceptibility to juvenile idiopathic arthritis and juvenile-onset systemic lupus erythematosus in Chinese children

Genetic factors play a crucial role in the immune response of juvenile idiopathic arthritis (JIA) and juvenile-onset systemic lupus erythematosus (JSLE). This study aimed to investigate the association of IL12B (rs3212227, rs6887695) and IL17 (rs2275913, rs763780) gene polymorphisms with the susceptibility of JIA and JSLE in Chinese children. A total of 303 healthy controls and 304 patients including 160 JIA and 144 patients were analyzed, and the genetic polymorphisms were genotyped by using a Sequenom MassArray system. There was a significant association between the IL12B rs3212227 genotype and the increased risk of JSLE (P = .01). For rs6887695, the minor allele C was significantly associated with the increased risk of JIA (odds ratio = 1.48, 95% confidence interval [CI] = 1.12–1.95, P = .005). Moreover, rs6887695 genotype was significantly associated with both JIA and JSLE susceptibility (P &lt; .05). Besides, IL12B haplotype GC significantly associated with the increased risk of JIA (P = .016). However, no significant difference was found between the IL17 (rs2275913, rs763780) gene polymorphisms and JIA or JSLE susceptibility (P &gt; .05). And similar genotype distributions of IL12B and IL17 polymorphisms were found between the patients with nephritis and without nephritis in JSLE (P &gt; .05). Our results indicated that IL12B polymorphisms was associated with an increased risk for the development of JIA and JSLE in Chinese children, highlighting the involvement of inflammation in the pathogenesis of JIA and JSLE. Moreover, there was a risk haplotype in IL12B which could increase the risk of JIA.

Health Related Quality of Life in Juvenile-Onset Systemic Lupus Erythematosus: A Questionnaire-Based Study

ObjectivesThis study aimed to evaluate health related quality of life (HRQOL) in Egyptian children with systemic lupus erythematosus (SLE) using 3 different tools.MethodsIn this questionnaire-based study, 100 children with SLE were included. HRQOL was assessed using the Pediatric Quality of Life Inventory Generic Core Scales (PedsQL™ 4.0 GCS), PedsQL™ 3.0 Rheumatology Module (PedsQL3-RM) and the Simple Measure of the Impact of Lupus Erythematosus in Youngsters (SMILEY). SLE disease activity index (SLEDAI) was used to evaluate activity and SLE International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) was used to evaluate chronic damage.ResultsAll mean scores of PedsQLTM4.0 GCS domains in SLE patients were lower than published normative data and previously published results of Egyptian healthy controls (p < 0.001). All mean scores of PedsQL-3RM domains were significantly lower than published normative data except for the treatment and pain and hurt domains (p = 0.1, 0.2 respectively). SMILEY scores were low and the lowest domain scores was “Burden of SLE”. Longer duration of illness, higher cumulative steroid doses, higher SLEDAI and SDI scores and presence of obesity were associated with lower scores for all 3 tools (p < 0.001).Conclusion for PracticeThe Arabic copies of PedsQL™ 4.0 GCS, PedsQL3-RM and SMILEY are easily used for Arabic speaking subjects and easily interpreted by physician and can be implemented for frequent monitoring of SLE HRQOL. Controlling the disease activity and using lowest doses of steroids and other immunosuppressive drugs are the corner stone strategies for improving HRQOL in SLE children.

Juvenile-onset systemic lupus erythematosus and MEFV polymorphism: A case–control association study among Iranian children

Introduction and objectivesThis study is designed to evaluate the potential influences of Mediterranean fever gene (MEFV) gene polymorphism on systemic lupus erythematosus (SLE) in a cohort of juvenile patients. A case–control study was performed on Iranian patients with a mixed ethnicity population. Patients and methodsGenotypes of 50 juvenile cases, and 85 healthy controls were investigated for identifying M694V and R202Q polymorphism. Genotyping was done utilizing amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to detect M694V and R202Q mutations, respectively. Main findingsOur study indicates significant differences in the alleles and genotypes frequencies of MEFV polymorphism between SLE patients and healthy controls (P<0.05). Also, an association was found between renal involvement (50% vs. 8.3%, P=0.000, OR=0.91, 95% CI=0.30–0.278) in juvenile SLE patients and M694V polymorphism incident; But there was no association with other clinical manifestations. Principal conclusionWe found a significant association between R202Q and M694V polymorphism of the MEFV gene and susceptibility to SLE in the studied population; However, further studies on detailed characterization of these polymorphisms’ impacts on the key elements responsible for SLE pathogenesis is of great importance.

Juvenile-onset systemic lupus erythematosus and MEFV polymorphism: A case–control association study among Iranian children

Juvenile-onset systemic lupus erythematosus and MEFV polymorphism: A case–control association study among Iranian children

The role of hsa_circ_0008945 in juvenile-onset systemic lupus erythematosus

Backgroundcircular RNAs (circRNAs) play a crucial role in many physiological and pathological processes including juvenile-onset systemic lupus erythematosus (JSLE). The aim of this study is to investigate the role of circRNA hsa_circ_0008945 in JSLE and evaluate its significance as diagnosing biomarker.MethodsRT-qPCR was applied to detect the level of circ_0008945 in JSLE and controls. The Spearman correlation test assessed the correlation between circ_0008945 and clinical variables. The receiver operating characteristic (ROC) curve was calculated for evaluating the diagnostic value. Overexpression or knockdown of circ_0008945 in primary peripheral blood mononuclear cells (PBMCs) was performed to further examine its function in apoptosis.ResultsRT-qPCR revealed that there were significantly higher levels of hsa_circ_0008945 in PMBCs from JSLE patients (p < 0.001) compared to healthy controls. In addition, there were significant associations between hsa_circ_0008945 level and the level of C3, C4, anti-ds DNA, IgG, CRP and ESR (p < 0.05) but not associated with the level of Ig A and Ig M. ROC curve of the circ_0008945 showed that the AUC was 0.790 and it may potentially be used as a novel biomarker for the diagnosis of JSLE. The results showed that overexpression of circ-0008945 increased the apoptosis of PBMCs while knockdown of circ-0008945 by siRNA decreased the apoptosis of PBMCs, supporting that circ-0008945 promoted the apoptosis in PBMCs and contributed to the pathogenesis of JSLE.ConclusionThe role of circ_0008945 was first investigated in JSLE and proposed herein their possible contribution to the pathogenesis of JSLE. This study provides not only novel insight into the pathological mechanisms but also the potential value as a useful biomarker for JSLE.

OA40 Predicting cardiovascular disease risk in children and adolescents with juvenile-onset systemic lupus erythematosus using the APPLE (Atherosclerosis Prevention in Paediatric Lupus Erythematosus) clinical trial cohort

Abstract Background/Aims The risk of developing cardiovascular disease (CVD) through atherosclerosis in juvenile-onset systemic lupus erythematosus (JSLE) patients is significantly increased. This study aimed to stratify and characterise JSLE patients at elevated CVD risk using patient/disease-related factors and metabolomic data from patients recruited to the APPLE (Atherosclerosis Prevention in Paediatric Lupus Erythematosus) clinical trial, designed to assess atherosclerosis development. Methods Unsupervised hierarchical clustering was performed to stratify patients by arterial intima-media thickness (IMT) measurements at baseline (N = 151) and carotid (c)IMT progression over 36 months (placebo arm only, N = 60). Baseline metabolomic profiles (∼250 serum metabolites) were compared between clusters using conventional statistics, univariate logistic regression, sparse Partial Least-Squares Discriminant Analysis (sPLS-DA) and random forest classifier. An independent cohort (UCL-JSLE cohort, N = 89) with matching metabolomics, immunophenotyping and proteomics, was used to validate the discovered CVD risk-related signatures from the APPLE cohort. Results Baseline IMT stratification identified 3 clusters with high, intermediate, and low baseline IMT measurements and progression trajectories over 36 months, each having distinct racial/BMI/household education/income characteristics. Analysis of cIMT progression over 36 months identified 2 patient groups with high and low IMT progression. Unique metabolomic profiles differentiated high and low cIMT progression groups, with a good discriminatory ability (0.81 AUC in ROC analysis) using the top 6 metabolites (total cholesterol esters, total cholesterol, phospholipids in small LDL particles, total cholesterol in small LDL particles, free cholesterol in medium LDL particles, and total lipids in small LDL particles) selected from the analysis. cIMT progression over 36 months in the placebo group correlated positively with baseline disease activity (SLEDAI), damage score (SLICC), white blood cell count, serum complement C3, blood pressure (both systolic and diastolic) and BMI. Metabolomics signatures discovered from the APPLE cohort were applied to stratify JSLE patients in the validation cohort (UCL-JSLE), where 3 groups were identified with distinct metabolomics profiles indicating JSLE patients with high risk (N = 20), intermediate risk (N = 43) and low risk (N = 26) CVD-risk. Significant differences were observed in the frequency of classical monocytes (p = 0.015) and nonclassical monocytes (p = 0.005) when comparing the high and low CVD risk groups in the UCL-JSLE cohort. Conclusion Complex analysis of IMT patterns and progression in the APPLE trial cohort identified novel key determinants that could guide further research for CVD-risk stratification in JSLE. Disclosure J. Peng: None. G.A. Robinson: None. S.P. Ardoin: None. L.E. Schanberg: None. O. Carra: None. E. Jury: None. C. Ciurtin: None.

OA12 Comparing disease manifestations and outcomes in juvenile-onset SLE and adult-onset SLE patients: a nested case-control study within a Singapore cohort

Abstract Background/Aims To compare disease manifestations and outcomes of juvenile-onset SLE (jSLE) and adult-onset SLE (aSLE) patients using a nested case-control study of patients in a Singapore cohort. Methods A prospective cohort of SLE patients was established at Tan Tock Seng Hospital from 1 January 2002 to 31 December 2017. Sociodemographic, clinical, laboratory and treatment data were collected according to a standardised protocol. jSLE patients (≤18 years old) were selected from this cohort and matched for gender and disease duration in a 1:1 ratio with aSLE patients. Data from the enrolment visit (V0) and last visit (VL) were analysed in this study. Results There were 148 jSLE patients with sufficient information for analysis who were matched with 148 aSLE patients. Fever and lymphadenopathy (p &amp;lt; 0.001) and hypocomplementemia (p = 0.002 at V0) were significantly more common in jSLE, while cardiovascular manifestations were significantly more common in aSLE patients (p = 0.008 at VL). Disease activity measured by the SLE Disease Activity Index (SLEDAI) was higher in the jSLE group at V0 (median SLEDAI 4 vs 2, p=0.05) and at VL (median SLEDAI 2.5 vs 0, p = 0.007). A significantly higher proportion of jSLE patients received immunosuppressants (intravenous cyclophosphamide, mycophenolate mofetil, azathioprine and ciclosporin) (p = 0.003 at V0, p &amp;lt; 0.001 at VL) and intravenous methylprednisolone (p &amp;lt; 0.001 at V0 and VL) compared to aSLE patients. Conclusion A higher proportion of jSLE patients have fever, lymphadenopathy, hypocomplementemia, or more active disease requiring greater use of immunosuppressants compared to aSLE patients. Early diagnosis and treatment of jSLE may prevent development of major organ involvement, in particular renal and neuropsychiatric. Disclosure B.Y. Thong: None. Y. Khong: None. X. Lim: None. H. Howe: None.

Significance of the weighted complement domain of the EULAR/ACR classification criteria in juvenile onset systemic lupus erythematosus.

We aimed to compare the clinical and laboratory characteristics of patients with SLE according to the weighted complement status of the EULAR/ACR criteria and investigate whether different weighting of the complement status at disease onset is associated with outcomes. Patients diagnosed with juvenile onset SLE who fulfilled the 2019 EULAR/ACR classification criteria were retrospectively analyzed. Among 43 patients included, hypocomplementemia was observed in 37 (86%), mostly with a low level of both complement C3 (C3) and complement C4 (C4) (53.5%). In patients with low levels of both C3 and C4, more common cutaneous (65.2% vs 28.6%, p: 0.045), musculoskeletal involvement (78.3% vs 42.9%, p: 0.039), autoimmune hemolytic anemia (52.2% vs 14.3%, p: 0.035), positive anti-dsDNA (65.2% vs 21.4%, p: 0.017) and anti-Sm antibodies (60.9% vs 21.4%, p: 0.04) were observed. In addition these patients had higher scores from the 2019 EULAR/ACR classification criteria (26 vs 15.5, p: < 0.0001). Remission and flare rates, and SLE associated damage were not differed according to the complement status in patients with hypocomplementemia. Observation of more frequent clinical and serological activity with higher total scores from the EULAR/ACR classification criteria supported the higher scoring of patients with low C3 and C4 in the weighted criteria. However, since significant number of patients did not exhibit low complement C4, and the frequency of kidney involvement did not differ according to the weighted complement status, complement C3 might be suggested as a more important diagnostic tool in patients with juvenile onset SLE. Also, weighted complement status at onset did not seem to affect the disease outcomes.

Anorexia Nervosa in Juvenile Systemic Lupus Erythematosus (SLE): A Causality Dilemma.

Juvenile-onset systemic lupus erythematosus (jSLE) is an autoimmune disorder with multifaceted clinical findings in different organ systems. Neuropsychiatric manifestations affect more than half of SLE patients, and there is increasing evidence that anorexia nervosa (AN), a feeding and eating disorder (FED) characterized by significantly reduced energy intake, is among them. Herein, a review of the literature on the potential association between jSLE and AN was performed. Reported clinical cases were identified, and putative pathophysiological mechanisms were sought that could potentially explain the observed relationship between these two pathological entities. Four reports of isolated cases and a case series including seven patients were identified. In this limited patient pool, the diagnosis of AN preceded that of SLE in the majority of cases, whereas in all cases both entities were diagnosed within a time span of two years. Many explanations for the observed relationships have been proposed. AN has been associated with the stress of chronic disease diagnosis; on the other hand, the chronic inflammation associated with AN may contribute to the development/appearance of SLE. Adverse childhood experiences, concentrations of leptin, shared autoantibodies, and genetic traits appear to be important factors in this well-established interplay. In essence, it seems important to increase clinician awareness of the concomitant development of AN and SLE and invite further research on the subject.

Autoantibody-based subgroups and longitudinal seroconversion in juvenile-onset systemic lupus erythematosus

ObjectiveTo explore the clinical value of autoantibody-based subgroup framework and the trend of autoantibody fluctuation in juvenile-onset SLE (JSLE).MethodsEighty-seven patients with JSLE were retrospectively collected and divided into subgroups via...