SLE Patients Research Articles

Evaluation of lipid profile in systemic lupus erythematosus and relation with interleukin-10

Objectives: To detect pattern of dyslipidemia in patients of SLE and clarify the correlation between lipid profile with disease activity, inflammatory factors, and cytokines. Materials and Methods: Blood collected from 65 SLE patients and 30 healthy controls measured Th-17, IL-17, IL-10 by flow cytometer. Statistical analysis: The relationship of lipid profile with various parameters was analyzed and stepwise logistic regression was used to assess the predictors of dyslipidemia. Results: The unique pattern of dyslipidemia in high disease activity was a significant decline in high density lipoprotein (HDL) and apolipoprotein A1 when compared to low disease activity. IL-10 was the strongest predictor for HDL (CI: -0.31 to -0.20, p=0.000). This is the first time a relation of IL-10 with HDL has been determined in SLE patients. Conclusions: IL-10 elevation is associated with decline in HDL. Since IL-10 appears to be a potential modulator of dyslipidemia in SLE, it can serve a new target for lipid metabolism to reduce cardiovascular risk in SLE.

#3019 Hepcidin and erythropoietin along with iron indices to asses anemia in lupus nephritis population

Abstract Background and Aims There is a broad spectrum of hematologic manifestations in SLE including lymphopenia, anemia, thrombocytopenia, or pancytopenia. lymphadenopathy and splenomegaly are also identified especially with high disease activity. Anemia of chronic disease, representing approximately one third of the cases in patients with SLE. Santacruz et al, also reported that iron deficiency anemia is also a common cause, usually caused by blood loss. serum hepcidin levels are high in patients with CKD, and are associated with erythropoiesis stimulating agent resistant anemia due to the inability of stored iron to be accessed for erythropoiesis, they are also high in autoimmune diseases as SLE. we evaluated anaemia in lupus nephrites population by assessing the level of hepcidin, erythropoietin along with iron study Method in this observational study We identified 100 patients with SLE and diagnosed as lupus nephritis by means of renal biopsy ISN/RPS classification 2004 with some missed data about biopsy details, the patients assessed for anaemia by haemoglobin level, iron study (TSAT, ferritin), hepcidin (10-120 μg/L) and erythropoietin level (3-36 IU/L). Demographics, disease characteristics and comorbidities were ascertained and adjusted for. Results 52 % of patients with SLE, LN (mean age 37.85 (9.40) years, 94 % female,) had Hgb<12 g/dl. The two groups of patient were comparable in disease duration but anemia had higher disease activity than patients with normal Hgb (p. value 0.9, 0.001 ). Furthermore, incidence of DM and HTN wasn't have statical significant, laboratory investigation showed anemia is microcytic hypochromic with low TSAT, hepcidin is almost high in 72% of all patients but wasn't significantly different between the two groups but erythropoietin level was normal in 100% of patients in both groups. Conclusion Patients with SLE and LN have an increased prevalence of anemia due to different factors. Our data suggest that iron deficiency anaemia was prevalent in the study group which may be due to high hepcidin level in those group of patient or blood loses especially the majority were females, erythropoietin level as marker of anaemia in lupus nephritis patient had been found to be not an indicator, its receptor resistance or antibodies found in SLE patients.

#610 Alterations in frequency and function exhausted memory B cells in lupus nephritis and systemic lupus erythematosus

Abstract Background and Aims Various B cell abnormalities have been implicated in the pathogenesis of LN, and our previous studies have demonstrated that memory B cells assume pathogenic relevance in disease relapse. Memory B cell exhaustion is a B lymphocyte aberration initially reported in chronic human immunodeficiency virus (HIV) infection, and was later also observed in chronic graft versus host disease (cGVHD) and autoimmune disorders. The pathogenic roles of exhausted memory B cells in LN and disease relapse remains unclear. We will validate the significance role of exhausted B cell in the pathogenesis of LN. Method Classical memory (CD19 + CD21 + CD27+) and exhausted B cells (CD19 + CD21 – CD27–) were measured in LN patients with multiple relapses (MR) (n=15) or no relapse (NR) (n=15) during disease remission. B cell-related cytokines, homing and inhibitory receptors, proliferation and calcium mobilization in classical and exhausted memory B cells were also assessed. Using single-cell RNA sequencing data from NIH and GEO, we also performed bioinformatics analysis to identify genes and pathways relevant to memory and exhausted B cells in SLE, LN and healthy controls. Results The MR group exhibited higher proportion of circulating exhausted memory B cells compared to NR. Blood levels of IL-6, BAFF and IL-21 in MR patients were higher than the NR group. The MR had higher blood levels of Siglec-6, CXCR3 and CD62L than the NR group. Expression of inhibitory receptors CD22, CD85j, CD183 and FCRL4 in exhausted B cells were increased in the MR group compared to the NR group. Exhausted B cells from MR patients also showed decreased proliferation compared to NR patients and impaired calcium mobilization in response to B-cell receptor triggering. STAT1, XAF1, MX1, IFI44L, EPSTI1, LCP1, OAS1, NEAT1, IFI16, IFI44 in exhausted B cells and XAF1, MX1, IFI44L in memory B cells play a pathogenic role in LN patients (Figs. 1 and 2). SLE patients also show increased proportion of exhausted B cells compared to healthy control and the expression of STAT1, XAF1, MX1, IFI44L correlate positively with the proportion of exhausted B cells. Conclusion Our results suggested that altered numbers and function of exhausted B cells may have pathogenic significance in SLE and LN.

Efficacy and safety of telitacicept therapy in systemic lupus erythematosus with hematological involvement.

To evaluate the efficacy and safety of telitacicept in SLE patients specifically with hematological involvement. A total of 22 patients with SLE and hematological involvement were included in this study. These patients received telitacicept in addition to standard therapy. We compared their demographic characteristics, clinical manifestations, and laboratory indicators before and after the administration of telitacicept. A total of 22 patients received telitacicept treatment for a median duration of 10.4months (ranging from 6 to 19months). Following telitacicept therapy, significant improvements were observed in various parameters compared to baseline. Specifically, white blood cell count increased from (3.98 ± 1.80) 109/L to (6.70 ± 2.47) 109/L, (P = 0.002), hemoglobin levels increased from (100 ± 19) g/L to (125 ± 22) g/L, (P < 0.001), and platelet count increased from (83 ± 60) 109/L to (161 ± 81) 109/L, (P = 0.004). SLE Disease Activity Index (SLEDAI) scores decreased from 12(5,15) to 0(0,4), (P < 0.001). Additionally, C3 and C4 levels showed improvement. Telitacicept treatment also resulted in a significant reduction in serum IgG levels and daily prednisone dosage. Only one adverse event (4.5%) was reported during the treatment, which was a urinary tract infection. The combination of telitacicept and standard treatment demonstrated significant improvements in anemia, as well as increased leukocyte and platelet levels in patients with SLE and hematological involvement. Importantly, the observed adverse events were manageable and controllable. Key Points • Telitacicept effectively improves anemia, clinical outcomes, and increases leukocyte and platelet counts. • Treatment with telitacicept leads to decreased levels of lgG, IgA, anti-dsDNA, and SLEDAI scores, while serum complement C3 and C4 returned to normal. • During the follow-up period there were observed changes in individual parameters, clinical symptoms, and organ involvement, all without significant adverse events.

Treatment Patterns for End-Stage Kidney Failure in Patients With Systemic Lupus Erythematous.

This study aims to examine the treatment patterns of end-stage kidney disease (ESKD) among SLE patients and to compare the outcome of hemodialysis (HD) and peritoneal dialysis (PD). SLE patients identified from the national administration dataset in 2005-2021 were linked to the Australia and New Zealand Dialysis and Transplant Registry to identify ESKD cases. The adjusted odds ratio of having PD instead of HD as the first treatment for ESKD for Asian, Māori, and Pacific compared with European/others was estimated with the logistic regression model. The adjusted hazards ratio of all-cause mortality for patients having PD first compared with HD first was calculated. Two hundred ten ESKD patients with SLE were identified. Two thirds (137/210) of the ESKD patients had HD as the first treatment, and one third (68, 32.4%) had PD first. Around 60% of Asian patients had PD as the first treatment, compared with 30% in other ethnic groups. The adjusted odds ratio of having PD as the first treatment for Asian patients compared with European/others was 3.00 (95% confidence interval, 1.16-7.73). The adjusted hazards ratio of all-cause mortality for patients in the PD group compared with the HD group was 0.60 (95% confidence interval, 0.37-0.97). Asian patients with ESKD were more likely to have PD as the first treatment. The optimal dialysis type for ESKD patients with SLE might be different from ESKD patients caused by other diseases. ESKD patients with SLE receiving PD first had superior outcomes than patients receiving HD first.

Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Clinical characteristics of systemic lupus erythematosus patients with adrenal hemorrhage.

Adrenal hemorrhage (AH) is a rare condition and severe cases can lead to acute adrenal insufficiency with potentially life-threatening consequences. AH can be caused by a variety of etiologic factors, including systemic lupus erythematosus and antiphospholipid syndrome (APS). The early identification and treatment of these patients improves their prognosis. The aims of this study were to analyze and summarize the clinical characteristics of systemic lupus erythematosus patients with AH. The clinical characteristics of 6 systemic lupus erythematosus patients complicated with AH admitted to Peking Union Medical College Hospital and Beijing Shijitan Hospital from May 2004 to April 2022 were retrospectively analyzed. The diagnosis of AH was based on computed tomography (CT) findings. Two patients had bilateral lesions, and the other 4 patients had unilateral lesions. The symptoms of adrenal insufficiency were observed in 2 patients. The frequent presenting symptoms were abdominal pain, lower abdominal distension, vomiting, weakness, fever, arthrodynia, and skin rash. Four patients had APS. Five patients (4 patients with APS and 1 patient without APS) had thromboembolic events. All patients received glucocorticoid and immunosuppressant therapy. Five patients were treated with anticoagulant therapy. Follow-up imaging examinations showed a partial or total regression of the lesions after treatment. In the proper clinical setting, having high clinical suspicion for AH, early diagnosis and timely management is crucial to avoid life-threatening adrenal insufficiency. Key Points • AH is a rare condition and severe cases may lead to death. It can be caused by a variety of etiologic factors, including SLE. • In patients with SLE, especially combined with APS, if they complain of abdominal pain, particularly when common gastrointestinal involvement is difficult to explain, a high index of clinical suspicion is needed for the diagnosis of AH. • Early identification of AH in SLE patients can improve their prognosis.

Association between systemic lupus erythematosus and osteoporosis: a mendelian randomization analysis

BackgroundSystemic Lupus Erythematosus (SLE) and Osteoporosis are two prevalent medical conditions. Previous studies have suggested a possible correlation between SLE and osteoporosis, though the underpinning causal relationship remains largely unknown. The current study aimed to elucidate the causal association between SLE and osteoporosis by employing a Mendelian randomization (MR) approach.MethodsWe performed two-sample MR analysis using the inverse variance-weighted (IVW), weighted median, and MR-Egger methods on publicly available summary statistics datasets using a SLE genome-wide association study (GWAS) as an exposure and osteoporosis GWASs in people with East Asia ancestry as outcomes. The pleiotropy and heterogeneity were examined using a variety of techniques, including the MR-Egger intercept, the MR-PRESSO approach, and the Cochran’s Q test.ResultsWe selected 26 single-nucleotide polymorphisms from a SLE GWAS as instrumental variables for osteoporosis. The IVW (p < 0.05) method results support a potential association between SLE and osteoporosis. MR-Egger intercept (p = 0.82) and MR-PRESSO global test (p = 0.80) did not suggest evidence of horizontal or directional pleiotropy. Cochran’s Q test (p = 0.78) showed that there was no heterogeneity between IVs.ConclusionThe results of MR analysis indicated that SLE is likely associated with an increased risk of osteoporosis incidence. Our findings highlight the need for increased awareness the potential risk of osteoporosis among SLE patients.

Neuropsychiatric prodromes and symptom timings in relation to disease onset and/or flares in SLE: results from the mixed methods international INSPIRE study

Neuropsychiatric symptoms in SLE and other systemic autoimmune rheumatic diseases (SARDs) are challenging to diagnose, attribute and manage. We investigated the timings of onset of a broad range of neuropsychiatric (NP) symptoms in relation to timing of SLE onset. In addition, we explored whether NP symptoms may be a prodrome to SARD onset and to subsequent flares. We collected patient reports of the timing of their first episode of 29 NP symptoms relative to SLE non-NP symptom onset. Surveys (n=676 SLE patients and n=400 clinicians) and interviews (n=50 clinicians; and n=69 SARD patients, including 27 SLE patients) were completed from 2022 to 2023, and analysed using mixed methods. The majority of NP symptoms did not first present around the time of SLE onset, contrary to the prevailing view among many rheumatology participants and in the literature. For example, among patients who experienced hallucinations, 54% reported first presentation >1 year after disease onset. Patient interviews also revealed that a range of NP symptoms may be a prodrome to SLE/SARDs onset and later flares, including symptoms not represented in existing classification criteria. Evidence of a possible prodromal syndrome was elicited from those patients who experienced hallucinations. Of these, 61% (SLE) and 34% (other SARDs) reported increasingly disrupted dreaming sleep (usually nightmares) prior to their hallucinations. In-depth interviews revealed that progression of symptoms in flares showed a high degree of inter-patient variation, whilst symptom progression was often similar in individual patient's recurrent flares. Neuropsychiatric symptoms can first present at any stage in the SLE disease course. Attributional decisions should evaluate timings of NP symptoms in relation to timing of SLE/SARD symptom onset rather than time of diagnosis due to frequent diagnostic delays. Greater recognition of prodromal/early NP symptoms indicating impending SLE flares (and potentially other SARD flares) could enable quicker flare identification and treatment. The Lupus Trust.

Prevalence of major adverse cardiovascular events among Saudi patients with systemic lupus erythematosus compared with the general population: updates from the national SLE and PURE cohorts

ObjectiveThis study examined the prevalence of major adverse cardiovascular events (MACE) among Saudi patients with SLE and the general population and considered factors associated with such outcomes were taken into...

Prediction model for developing neuropsychiatric systemic lupus erythematosus in lupus patients.

This study aimed to construct a predictive model for assessing the risk of development of neuropsychiatric systemic lupus erythematosus (NPSLE) among patients with SLE based on clinical, laboratory, and meteorological data. A total of 2232 SLE patients were included and were randomly assigned into training and validation sets. Variables such as clinical and laboratory data and local meteorological data were screened by univariate and least absolute shrinkage and selection operator (LASSO) logistic regression modelling. After 10-fold cross-validation, the predictive model was built by multivariate logistic regression, and a nomogram was constructed to visualize the risk of NPSLE. The efficacy and accuracy of the model were assessed by receiver operating characteristic (ROC) curve and calibration curve analysis. Net clinical benefit was assessed by decision curve analysis. Variables that were included in the predictive model were anti-dsDNA, anti-SSA, lymphocyte count, hematocrit, erythrocyte sedimentation rate, pre-albumin, retinol binding protein, creatine kinase isoenzyme MB, Nterminal brain natriuretic peptide precursor, creatinine, indirect bilirubin, fibrinogen, hypersensitive C-reactive protein, CO, and mild contamination. The nomogram showed a broad prediction spectrum; the area under the curve (AUC) was 0.895 (0.858-0.931) for the training set and 0.849 (0.783-0.916) for the validation set. The model exhibits good predictive performance and will confer clinical benefit in NPSLE risk calculation. Key Points • Clinical, laboratory, and meteorological data were incorporated into a predictive model for neuropsychiatric systemic lupus erythematosus (NPSLE) in SLE patients. • Anti-dsDNA, anti-SSA, LYM, HCT, ESR, hsCRP, IBIL, PA, RBP, CO, Fib, NT-proBNP, Crea, CO, and mild contamination are predictors of the development of NPSLE and may have potential for research. • The nomogram has good predictive performance and clinical value and can be used to guide clinical diagnosis and treatment.

P152 Very Late Onset Systemic Lupus Erythematosus - Comparison with Younger Patients

Abstract Background/Aims Age has a significant impact on SLE. However, data on very late onset SLE (vlSLE) patients are scarce. We have characterized a large SLE patient cohort, followed for up to 45 years and compared the clinical and serological features at the different ages at diagnosis, focusing on those whose disease began at 60 or later. Methods We conducted an observational cross-sectional study at our SLE clinic. All patients with an SLE diagnosis evaluated from January 1978 to May 2023 were included. Patients were divided into four groups according to age at diagnosis: juvenile SLE (jSLE - &amp;lt;18 years); adult SLE (aSLE - 18-49 years); late SLE (lSLE - 50-59 years); vlSLE (≥ 60 years). Proportions and median values were compared using the X2 and Kruskall-Wallis tests, respectively. The probability of survival was estimated using the Kaplan-Meier method. Results 845 patients were enrolled. jSLE, aSLE, lSLE, and vlSLE groups included 153 (18.1%), 630 (74.6%), 47 (5.56%), and 15 (1.78%) patients, respectively. The mean age at diagnosis in vlSLE patients was 66.7 years. The female-to-male ratio tended to fall in the vlSLE group (4:1; p=0.282). vlSLE patients were mainly caucasian (93.3%; p&amp;lt;0.001) and had the lowest survival time (20.3 years; p&amp;lt;0.001). The most frequent clinical feature at follow-up in all groups was arthritis. Nevertheless, arthritis was least common among vlSLE patients (73.3%; p=0.043). Although malar and/or discoid rash, photosensitivity, and alopecia were less frequent among lSLE and vlSLE patients, the difference was not statistically significant. In contrast, oral ulcers tended to be more frequent in vlSLE patients (33.3%; p=0.537). vlSLE patients more commonly developed Sjögren’s syndrome (SS - 33.3%; p&amp;lt;0.001) and rheumatoid arthritis (RA - 13.3%; p&amp;lt;0.001). The prevalence of anti-phospholipid syndrome did not differ significantly between age groups. Neuropsychiatric involvement, and myositis did not occur among vlSLE patients. At diagnosis, vlSLE patients had the lowest prevalence of positive anti-dsDNA antibodies (26.7%; p=0.010) and low C3 levels (13.3%; p&amp;lt;0.001). Anti-SSA/Ro antibody positivity was also least common among vlSLE patients (26.7%; p=0.045). Although vlSLE patients also tended to have the lowest levels of ANA and anti-SSB/La antibody positivity, the difference was not statistically significant. Rheumatoid factor levels tended to increase with increasing age (p=0.066). Conclusion We report a detailed analysis of a large SLE under long term follow-up focusing on age at diagnosis related differences. Elderly patients differ from younger patients in clinical presentation. In vlSLE, female predominance is less pronounced; arthritis, anti-dsDNA antibodies and low C3 levels are less frequent. Concomitant SS and RA are more common. Our results confirm that older-onset SLE patients have lower disease activity. Nevertheless, these patients have the lowest survival rate. While very uncommon, SLE should not be excluded as a possible diagnosis in the elderly. Disclosure L. Viveiros: None. A. Neves: None. D.A. Isenberg: None.

P159 Development of digital neuropsychological battery: a use case in Indian SLE patients

Abstract Background/Aims While cognitive dysfunction and mood disorders are frequently reported as adverse effects of SLE, there is a scarcity of neuropsychological (NP) data for Asian SLE patients. Existing English-centric NP tests are inadequate for the linguistic and culturally diverse population. This study examines SLE's effects on mood and cognitive functions using an indigenously developed language-neutral digital NP test battery and validated anxiety, stress, depression and quality of life instruments. Methods We recruited SLE patients fulfilling 2012 SLE classification criteria as cases and caregivers (CG) and college students (CS) as controls aged above 18 years and at least 10th standard education. All participants provided written informed consent. Institutional ethics committees approved the study. The NP battery comprised five cognitive tasks: Montreal Cognitive Assessment (MoCA) and modified versions of attention network test (ANT), sustained attention to response task (SART), picture naming and N-back, and five psychological tests (PHQ-9, GAD-7, STAI-T, PSS-4 and WHOQOL-BREF). Mann-Whitney test with conditional Bonferroni's corrections was used to compare cases with CG and CS. Results Total of 142 volunteers (age: median = 25.0, IQR = 9.0, cases [n = 82], CG [n = 40] and CS [n = 20]) participated in the study. Cases exhibited delayed response latencies in N-back, SART, and picture naming tasks compared to controls. They demonstrated reduced accuracy in all N-back conditions, with significant differences observed in hit rate, miss rate, false alarms, and d-prime scores compared to CS with effect size ranging from 0.298 to 0.736 (Table 1). However, the difference was only significant in the 2-back condition compared to CG. Cases displayed lower accuracy in SART Go trials (higher omission errors) than controls but better inhibition in SART No-Go trials (lower commission errors). No differences were observed in alerting, orienting and executive control functions. Cases showed significantly lower scores in MOCA than controls. Cases reported poorer psychological health through increased anxiety and stress levels and reduced WHO-quality of life scores compared to CG. Conclusion Contrary to earlier research that often relied on isolated cognitive assessments, our pioneering approach introduces a tailored test battery to establish cognitive baselines for Indian SLE patients. Disclosure P. Singhal: None. P. Srivastava: None. L. Rajasekhar: None. N. Samhitha: None.

P160 High levels of CD19 expression is a characteristic feature of age-associated B cells in ageing and autoimmunity

Abstract Background/Aims Recent evidence implicates an important role for age-associated B cells (ABCs), defined as CD19+IgD-CD27-T-bet+ B cells, in healthy ageing, following viral infection and in active SLE. We know that co-receptors of the B cell receptor (BCR) such as CD19 and other activating receptors can influence B cell activation through distinct pathways. Therefore, we compared the expression of CD19 in B cell subpopulations including ABCs in ageing and SLE. Methods Peripheral blood was obtained from six young (&amp;lt;45 years) healthy participants, seven elderly (&amp;gt;65 years) healthy participants and eight patients with SLE (25-65 years). We performed flow cytometry on peripheral blood mononuclear cells to analyse the expression of extracellular and intracellular markers. We performed statistical analysis using GraphPad Prism v7. Results CD19hi B cell frequency was at least 10-fold higher in T-bet+ cells as a whole and particularly enriched in IgD-CD27-T-bet+, ABCs, in all groups, p &amp;lt; 0.05. The geometric mean fluorescent intensity (gMFI, expression) of CD40 was significantly lower in IgD-CD27-T-bet+ subpopulations compared to IgD-CD27-T-bet- B cell subpopulations in all groups (Table). In all groups, in CD19+T-bet+ cells, compared to CD19+T-bet- cells, there was a significantly increased frequency of IFNγR+ cells, TLR4+ cells, TLR7+ cells and TLR9+ cells (p &amp;lt; 0.05 for all) with remarkable difference noted in SLE patients for TLR7 and TLR9, p &amp;lt; 0.01 (Table). In the switched memory IgD-CD27+ and ABCs, TLR7 expression was significantly higher (p &amp;lt; 0.01) in SLE patients (mean 43.8% and 18.5% respectively) compared to elderly participants (mean 13.5% compared to 4.3% respectively). Conclusion High levels of expression of CD19 is a characteristic feature of ABCs and CD19hiT-bet+ cells predominantly belong to the IgD-CD27-T-bet+ ABC subpopulation. CD19hi IgD-CD27-T-bet+ cells also had significantly lower expression of CD40 and higher expression of IFNγR and TLR7 and TLR9, suggesting that CD19 plays a significant role in moderating activation of ABCs triggered through T-independent, IFNγR-TLR-T-bet pathway. Taken together with the significant role of CD19 in regulating signalling threshold of B cell activation, and its stable expression across different B cell developmental stages, these data provide compelling mechanistic rationale for targeting CD19 to deplete B cells, including potentially pathogenic age-associated, in autoimmune disease such as SLE. Disclosure K. Shah: None. V. Poon: None. S.J. Taylor: None. C. Klein: Corporate appointments; CK is employed by Roche. Shareholder/stock ownership; CK has patents and stock ownership at Roche. F. Kollert: Corporate appointments; FK is employed by Roche. Shareholder/stock ownership; FK has stock ownership at Roche. F. Schuler: Corporate appointments; FS is employed by Roche. Shareholder/stock ownership; FS has patents and stock ownership at Roche. S. Mathur: None. M. Castelino: None. D. Sen: None. J. Cambridge: None. M. Cragg: None. M. Leandro: None. A. Akbar: None. V. Reddy: None.

P026 Neurofascin antibodies complicating a case of severe systemic lupus erythematosus

Abstract Background/Aims Juvenile-onset systemic lupus erythematosus (jSLE) is an autoimmune disease that results in increased disease activity and damage compared to adult-onset SLE. There is increased medication burden, severe organ manifestations and higher incidence of renal, cardiovascular and neuropsychiatric (NP) involvement. Anti-nervous system (NS) antibodies are seen across immune mediated diseases including SLE. Myelin oligodendrocyte glycoprotein (MOG) and neurofascin (NF) 186 antibodies are particularly associated with higher frequencies of NP-SLE. These patients can present with the distinct clinical phenotype associated with that antibody (i.e., demyelination with MOG, neuropathy with NF186). Methods We present an SLE patient with progressive neurological features and anti-NF antibodies who responds well to ocrelizumab after modest response to initial immunotherapy. Results An 18 year old female has active jSLE including malar rash, alopecia, arthralgia, aphthous ulcers, headaches. She presents with lower limb and ascending abdominal paraesthesia and left 6th cranial nerve palsy alongside a recent respiratory tract infection. ANA 1:5120 homogenous pattern, high dsDNA, low C3 and C4, thrombocytopenia and antibodies to Sm, Ro, RNP, anti-Rib-P and strongly positive lupus anticoagulant antibodies and low titre anti-cardiolipin (aCL) IgG and IgM. Lumbar puncture is unremarkable. Nerve conduction studies (NCS) demonstrate progressive predominant motor inflammatory neuropathy without demyelination. CT, MRI brain and MRI spine are normal. She is treated as atypical Guillain-Barre Syndrome (GBS)/ Miller-Fischer with 5 days IV immunoglobulin 2g/kg and also for active SLE with 3 days 500mg IV methylprednisolone. She is intubated following worsening dysphagia, dysarthria, muscle weakness and reduced consciousness. Plasma exchange and pulsed cyclophosphamide are subsequently given. Eye and facial movements worsen with NCS showing worsening patchy axonal sensorimotor polyneuropathy. Serial MRI brain is suggestive of posterior reversible encephalopathy syndrome (PRES). Autonomic instability is seen with labile blood pressure and tachycardia. Given the unusual presentation, anti-NF antibodies are tested and identified at 1:3200 positive, NF155 and 186, both IgG1 and IgG2. Given previous adverse reaction to rituximab, she received ocrelizumab which lead to a marked improvement in her sensorimotor symptoms and functionality. C3 and C4 levels show considerable improvement which is sustained and dsDNA levels normalise. B cell depletion therapy was chosen following a small case series of patients with neurofascin antibodies who developed severe autoimmune neuropathies. Half of these patients responded well to rituximab. One proposed mechanism being the targeting of immature CD20+ B cells inhibits plasmablast generation, which may be responsible for neurofascin antibody production early on in the disease. Conclusion Anti-NS antibodies are seen in SLE patients and their presence can suggest increased frequency of NP-SLE suggesting a potential future role as a biomarker. One should consider anti-NF antibody testing in patients with a GBS-like illness with progressive neuropathy, respiratory involvement and autonomic dysfunction despite standard immunotherapy. Disclosure P. Yee: None. M. Mouyis: None.

P060 Multi-targeted therapy better in achieving a complete response in Lupus Nephritis: A systematic review and meta-analysis

Abstract Background/Aims Overall management of SLE and Lupus Nephritis (LN) has significantly improved over the last four decades. Recently great therapeutic strides have been made in management of LN using newer agents alone or combination of older therapies. With the availability of increased number of options choosing the optimal treatment regimen for LN has become challenging. Identifying the treatment regimen most effective in achieving complete response while minimizing adverse events is crucial for improving patient outcomes. We performed a systematic review and meta-analysis of clinical trials to explore optimal treatment regimen for LN. Methods The systematic review and meta-analysis were performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The literature search was conducted using public databases, such as the Cochrane Library, Web of Science and PubMed. Only randomized controlled clinical trials with either active comparator or placebo arms were included. Studies were excluded if they were retrospective, with no comparative drug arm, or less than 20 subjects per treatment response arm. Due to lack of agreed upon outcome measures, complete response (CR) and partial response (PR) criteria were determined as per the definition used by individual studies. Severe adverse reaction (SAE) frequencies were determined for each study for safety evaluation. Publication bias was detected by using funnel plots. Forest plots were used to summarize data, generate frequencies, odds ratio (OR), relative risks (RR) and corresponding 95% confidence intervals (CI) for each subgroup. Heterogeneity was evaluated using the I2 statistic, and labelled as low (25%), moderate (50%) and high (75%). All analyses were performed using R Statistical Software meta package (v4.2.1; R Core Team 2022). Results 31 eligible studies comprising 5495 SLE patients were included in analyses, the study characteristic features are shown in Table 1. Overall significant OR for achieving CR was reported by 10 studies (Figure 1). The highest effect was reported from study by Bao et.al using a combination of tacrolimus(TAC) and mycophenolate mofetil (MMF) compared to cyclophosphamide (CYC) (OR = 10.5, 95% CI 2.27; 48.76), another study using TAC+MMF combo reported OR = 2.49, 95% CI 1.59;3.88. The study by Ginzler et.al reported OR = 5.06 (95% CI 1.6:16.02) in favor of using MMF. Studies using CYC, voclosporin + MMF, and belimumab also reported significant OR for achieving CR. Data for the frequency of SAE were available in 22 studies. The frequency of SAE was not significantly different between treatments arms (OR: 1.07, 95%CI: 0.93-1.23, p &amp;gt; 0.05) Conclusion Our meta-analysis suggests multi-target treatment strategies, by adding calcineurin inhibitors to MMF may be better for achieving complete response in LN. Furthermore, using this combination treatment did not seem to increase the risk of side effects. Heterogenous treatment response criteria and variable comparator arms were major limiting factors of this study. Disclosure O. Pamuk: None. B. Shaikh: None. S. Khan: None. S. Abi Doumeth: None. S. Hasni: None.

ChatGPT4's proficiency in addressing patients' questions on systemic lupus erythematosus: a blinded comparative study with specialists.

The efficacy of artificial intelligence (AI)-driven chatbots like ChatGPT4 in specialized medical consultations, particularly in rheumatology, remains underexplored. This study compares the proficiency of ChatGPT4' responses with practicing rheumatologists to inquiries from patients with SLE. In this cross-sectional study, we curated 95 frequently asked questions (FAQs), including 55 in Chinese and 40 in English. Responses for FAQs from ChatGPT4 and five rheumatologists were scored separately by a panel of rheumatologists and a group of patients with SLE across six domains (scientific validity, logical consistency, comprehensibility, completeness, satisfaction level and empathy) on a 0-10 scale (a score of 0 indicates entirely incorrect responses, while 10 indicates accurate and comprehensive answers). Rheumatologists' scoring revealed that ChatGPT4-generated responses outperformed those from rheumatologists in satisfaction level and empathy, with mean differences of 0.537 (95% CI, 0.252-0.823; P < 0.01) and 0.460 (95% CI, 0.227-0.693; P < 0.01), respectively. From the SLE patients' perspective, ChatGPT4-generated responses were comparable to the rheumatologist-provided answers in all six domains. Subgroup analysis revealed ChatGPT4 responses were more logically consistent and complete regardless of language and exhibited greater comprehensibility, satisfaction and empathy in Chinese. However, ChatGPT4 responses were inferior in comprehensibility for English FAQs. ChatGPT4 demonstrated comparable, possibly better in certain domains, to address FAQs from patients with SLE, when compared with the answers provided by specialists. This study showed the potential of applying ChatGPT4 to improve consultation in SLE patients.

T cell expressions of aberrant gene signatures and Co-inhibitory receptors (Co-IRs) as predictors of renal damage and lupus disease activity

BackgroundSystemic lupus erythematosus (SLE) is distinguished by an extensive range of clinical heterogeneity with unpredictable disease flares and organ damage. This research investigates the potential of aberrant signatures on T cell genes, soluble Co-IRs/ligands, and Co-IRs expression on T cells as biomarkers for lupus disease parameters.MethodsComparative transcriptome profiling analysis of non-renal and end-stage renal disease (ESRD) phenotypes of SLE was performed using CD4 + and CD8 + cDNA microarrays of sorted T cells. Comparing the expression of Co-IRs on T cells and serum soluble mediators among healthy and SLE phenotypes.ResultsSLE patients with ESRD were downregulated CD38, PLEK, interferon-γ, CX3CR1, FGFBP2, and SLCO4C1 transcripts on CD4 + and CD8 + T cells simultaneously and NKG7, FCRL6, GZMB/H, FcγRIII, ITGAM, Fas ligand, TBX21, LYN, granulysin, CCL4L1, CMKLR1, HLA-DRβ, KIR2DL3, and KLRD1 in CD8 T cells. Pathway enrichment and PPI network analyses revealed that the overwhelming majority of Differentially Expressed Genes (DEGs) have been affiliated with novel cytotoxic, antigen presentation, and chemokine-cell migration signature pathways. CD8 + GZMK + T cells that are varied in nature, including CD161 + Mucosal-associated invariant T (MAIT) cells and CD161- aged-associated T (Taa) cells and CD161-GZMK + GZMB + T cells might account for a higher level of GZMK in CD8 + T cells associated with ESRD. SLE patients have higher TIGIT + , PD1 + , and lower CD127 + cell percentages on CD4 + T cells, higher TIM3 + , TIGIT + , HLA-DR + cell frequency, and lower MFI expression of CD127, CD160 in CD8 T cells. Co-IRs expression in T cells was correlated with soluble PD-1, PDL-2, and TIM3 levels, as well as SLE disease activity, clinical phenotypes, and immune-therapy responses.ConclusionThe signature of dysfunctional pathways defines a distinct immunity pattern in LN ESRD patients. Expression levels of Co-IRs in peripheral blood T cells and serum levels of soluble PD1/PDL-2/TIM3 can serve as biomarkers for evaluating clinical parameters and therapeutic responses.

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.

Musculoskeletal symptoms in systemic lupus erythematosus patients and their impact on health-related quality of life.

To evaluate the musculoskeletal (MSK) symptoms experienced by SLE patients and determine how those symptoms relate to their health-related quality of life (HRQoL). This is a cross-sectional study that was carried out on 103 adult SLE patients. sociodemographic, clinical, and therapeutic data were recruited. They were asked to complete the following: Nordic Musculoskeletal, Short-Form McGill Pain, and Lupus QoL Questionnaires. The mean age was 30.81 ± 9.44 years. There was a total of 86 females and 17 males (F: M:5:1). Almost all the patients reported MSK symptoms (96.1%). The maximum number of patients reported pain in the right and left wrist and hand (64.1%, 63.1%, respectively). One-fourth (25.2%) described at least five bodily sites of MSK symptoms, while 70.9% had more than five sites of MSK symptoms. Most of the patients described the pain as discomforting (40.8%). Patients with MSK symptoms scored significantly worse in all domains. In addition, the QoL scores of patients with more than 5 body sites of MSK symptoms were significantly lower than those of patients with fewer than 5 sites of MSK symptoms. SLE patients have a high MSK burden, and MSK symptoms have a negative impact on HRQoL in these patients.