Cohort Of Systemic Lupus Erythematosus Patients Research Articles

Cryptogenic Organizing Pneumonia Is Associated With Increased Mortality Risk in Hospitalizations for Systemic Lupus Erythematosus (SLE): A National Inpatient Sample Analysis.

Background This study analyzed the incidence, characteristics, and mortality risk associated with cryptogenic organizing pneumonia (COP) among hospitalizations for systemic lupus erythematosus (SLE) with lung involvement. Methods Adult hospitalizations from the 2016-2020 nationwide inpatient sample were analyzed using relevantInternational Classification of Diseases (ICD)-10 codes for SLE with lung involvement (M32.13) and COP (J84.116). We compared baseline characteristics of individuals with SLE and COP to those of other lung involvements using Chi-square tests for categorical variables and the Wilcoxon rank sum test for continuous variables. A Cox proportional hazards model was used to assess the risk of developing COP in the pooled cohort of SLE patients. The impact of COP on SLE mortality was assessed using multivariate logistic regression adjusting forillness severity, baseline risk of mortality at admission, and patient- and hospital-level covariates. Results Of 40,356 admissions for SLE, 3,175 (7.9%) were due to lung involvement, with COP identified in 570 cases (17.9%). Compared with otherlung involvement in SLE, individuals with COP were significantly older (mean age: 65 vs. 44.3 years; p<0.001), mostly female (515; 90.4% vs. 2,305 males; 88.5%; p=0.572), had a greater baseline risk of mortality [diagnosis-related groups (DRG) major or extreme likelihood of dying: 360; 63.1% vs. 1,133; 43.5%; p<0.001], and had a higher prevalence of peripheral vascular disease (25; 4.4% vs. 39; 1.5%; p<0.001), and lower prevalence of lymphocytopenia (45; 7.9% vs. 359; 13.8%; p=0.001), and hypothyroidism (44; 7.8% vs. 357; 13.7%; p=0.001). Predictors of COP included female sex [adjusted hazard ratio (AHR): 1.46; 95% confidence interval (CI): 1.12-2.96; p=0.022]; hospitalizations occurring in the third quarter of the year (AHR: 1.37; 95% CI: 1.05-2.23; p=0.038); hospital stays of six days or longer (AHR: 1.71; 95% CI: 1.06-2.77; p=0.029); undergoing five or more procedures during the same hospitalization (AHR: 1.56; 95% CI: 1.26-3.56; p=0.041); coexisting lymphocytopenia (AHR: 1.92; 95% CI: 1.16-3.19; p=0.011); need for mechanical ventilation (AHR: 1.60; 95% CI: 1.48-3.93; p=0.049), presence of another autoimmune disorder (AHR: 1.37; 95% CI: 1.15-4.29; p=0.040), and being hospitalized at private, investor-owned hospitals (AHR: 2.62; 95% CI: 1.03-6.64; p=0.043). Mortality in SLE with lung involvement was correlated with age ≥ 60 years [hazard ratio (HR) (95% CI) 1.16 (1.05-1.56); p=0.012], coexisting lupus nephritis [HR (95% CI), 2.44 (2.04-3.49); p=0.031], cancer [HR (95% CI), 3.49 (2.19-5.79); p<0.001], liver disease [HR (95% CI), 9.82 (4.79-12.57); p<0.001]; immune deficiency [HR (95% CI), 2.22 (2.02-3.11); p=0.031], hypothyroidism [HR (95% CI), 4.67 (1.47-7.75); p=0.009], and high blood pressure [HR (95% CI), 3.15 (2.83-4.51); p<0.001]. In the multivariable analysis, COP remained significantly associated with an increased risk of mortality [AHR (95% CI), 1.43 (1.16-2.74); p=0.031]. The incidence of COP did not significantly impact hospitalization costs ($US 94,772 ± 14,759 vs. 95,982 ± 32,625; p=0.954) or length of stay (mean length of hospital stay: 8.3 vs.6.8 days; p=0.147). Conclusion Cryptogenic organizing pneumoniawas associated with 1% of all hospitalizations for SLE and 18% of cases involving lung complications in SLE. The presence of COP significantly increased the risk of mortality in SLE patients with lung involvement.

Oculometric biomarkers of visuomotor deficits in clinically asymptomatic patients with systemic lupus erythematosus undergoing long-term hydroxychloroquine treatment.

This study examines a set of oculomotor measurements, or "oculometric" biomarkers, as potential early indicators of visual and visuomotor deficits due to retinal toxicity in asymptomatic Systemic Lupus Erythematosus (SLE) patients on long-term hydroxychloroquine (HCQ) treatment. The aim is to identify subclinical functional impairments that are otherwise undetectable by standard clinical tests and to link them to structural retinal changes. We measured oculomotor responses in a cohort of SLE patients on chronic HCQ therapy using a previously established behavioral task and analysis technique. We also examined the relationship between oculometrics, OCT measures of retinal thickness, and standard clinical perimetry measures of visual function in our patient group using Bivariate Pearson Correlation and a Linear Mixed-Effects Model (LMM). Significant visual and visuomotor deficits were found in 12 asymptomatic SLE patients on long-term HCQ therapy compared to a cohort of 17 age-matched healthy controls. Notably, six oculometrics were significantly different. The median initial pursuit acceleration was 22%, steady-state pursuit gain 16%, proportion smooth 7%, and target speed responsiveness 31% lower, while catch-up saccade amplitude was 46% and fixation error 46% larger. Excluding the two patients with diagnosed mild toxicity, four oculometrics, all but fixation error and proportion smooth, remained significantly impaired compared to controls. Across our population of 12 patients (24 retinae), we found that pursuit latency, initial acceleration, steady-state gain, and fixation error were linearly related to retinal thickness even when age was accounted for, while standard measures of clinical function (Mean Deviation and Pattern Standard Deviation) were not. Our data show that specific oculometrics are sensitive early biomarkers of functional deficits in SLE patients on HCQ that could be harnessed to assist in the early detection of HCQ-induced retinal toxicity and other visual pathologies, potentially providing early diagnostic value beyond standard visual field and OCT evaluations.

Study of Serum Complement 3 Split Product iC3b /C3 Ratio in a Cohort of Systemic Lupus Erythematosus Patients

Abstract Background Systemic lupus erythematosus (SLE) is a chronic autoimmune systemic disease that causes widespread multi organ inflammation. The exact cause of SLE remains unclear; however, genetic, hormonal, and environmental factors contribute to the development of the disease. Aim of the Work The aim of this study is to measure the ratio of complement split product iC3b to C3 and its relation to disease activity and lupus nephritis in a cohort of SLE patients. Patients and Methods This study is a Cross sectional case control study conducted in internal medicine and Rheumatology unit, Ain Shams university hospital and Rheumatology unit, Maadi military hospital. Our study included. Results The present study shows that female were (76%) in active group of SLE patients and (60%) in inactive group while male were (24%) and (40%) respectively. with no significant difference. The mean of Disease Duration was (5.66 ± 1.97) with a range from 3 and 10 years in active group of SLE patients and (5.08 ± 1.54) with a range from 3 and 9 years in inactive group. with no significant difference. Regarding clinical manifestations of SLE the present study shows that active group of SLE patients had statistically highly significant increase in incidence of lupus nephritis, arthritis, serositis, oral ulcers, malar rash (p &amp;lt; 0.001) with significant increase in incidence of alopecia and neurological manifestations (p &amp;lt; 0.05). The current study shows that active group of SLE patients had statistically significantly higher mean ESR, anti-DNA titre, 24hr urinary proteins, serum creatinine, serum urea, and GFR levels (p = 0.000) than inactive group, Also active group had significant leucopenia, anemia (p = 0.000, 0.005 respectively) and C3 was significantly more consumed than inactive group (p &amp;lt; 0.05) Conclusion The ratio of complement split product iC3b to C3 concentrations correlates with the extent of SLE disease activity more than C3 alone. Furthermore, the iC3b:C3 ratio may discriminate between patients with lupus nephritis and patients without lupus nephritis. Detection of SLE disease activity and lupus nephritis by iC3b/C3 ratio help to make a proper decision in management to induce remission.

Factor H-related protein 1 in systemic lupus erythematosus.

Factor H (FH) is a major soluble inhibitor of the complement system and part of a family comprising five related proteins (FHRs 1-5). Deficiency of FHR1 was described to be linked to an elevated risk of systemic lupus erythematosus (SLE). As FHR1 can partially antagonize the functionality of FH, an altered FHR1/FH ratio could not only enhance SLE vulnerability but also affect the disease expression. This study focuses on the analysis of FH and FHR1 at a protein level, and the occurrence of anti-FH autoantibodies (anti-FH) in a large cohort of SLE patients to explore their association with disease activity and/or expression. We assessed FH and FHR1 levels in plasma from 378 SLE patients compared to 84 healthy controls (normal human plasma, NHP), and sera from another cohort of 84 healthy individuals (normal human serum, NHS), using RayBio® CFH and CFHR1 ELISA kits. Patients were recruited by the Swiss SLE Cohort Study (SSCS). Unmeasurable FHR1 levels were all confirmed by Western blot, and in a subgroup of patients by PCR. Anti-FH were measured in SLE patients with non-detectable FHR1 levels and matched control patients using Abnova's CFH IgG ELISA kit. Overall, FH and FHR1 levels were significantly higher in healthy controls, but there was no significant difference in FHR1/FH ratios between SLE patients and NHPs. However, SLE patients showed a significantly higher prevalence of undetectable FHR1 compared to all healthy controls (35/378 SLE patients versus 6/168 healthy controls; p= 0.0214, OR=2.751, 95% CI = 1.115 - 8.164), with a consistent trend across all ethnic subgroups. Levels of FH and FHR1, FHR1/FH ratios and absence of FHR1 were not consistently associated with disease activity and/or specific disease manifestations, but absence of FHR1 (primarily equivalent to CFHR1 deficiency) was linked to the presence of anti-FH in SLE patients (p=0.039). Deficiency of FHR1 is associated with a markedly elevated risk of developing SLE. A small proportion of FHR1-deficient SLE patients was found to have autoantibodies against FH but did not show clinical signs of microangiopathy.

Diagnostic Values of METTL1-Related Genes and Immune Characteristics in Systemic Lupus Erythematosus.

Methyltransferase like 1 (METTL1) regulates epitranscriptomes via the m7G modification in mammalian mRNA and microRNA. Systemic lupus erythematosus (SLE) is caused by abnormal immune reactivity and has diverse clinical manifestations. RNA methylation as a mechanism to regulate gene expression is widely implicated in immune regulation. However, the role of m7G in immune response of SLE has not been extensively studied. Expression of METTL1 was identified in the public dataset GSE122459 and validated in an independent cohort of SLE patients. We investigated the association between METTL1-expression and clinical manifestations of SLE. Subsequently, differentially expressed genes (DEG) that were correlated with METTL1-expression in GSE122459 were used for functional enrichment analysis. The correlation between infiltrating immune cells and METTL1, as well as candidate biomarkers identified to be correlated with either METTL1 or immune cell infiltration were assessed by single-sample GSEA. Potential mechanisms were explored with Gene ontology and KEGG pathway enrichment. Diagnostic performances of candidate biomarkers in SLE were analyzed. The mRNA and protein expression of METTL1 in SLE patients were significantly decreased in both datasets. METTL1-coexpressed DEGs were enriched in several key immune-related pathways. Activated CD8 T cells, activated CD4 T cells, memory B cells and type 2 helper T cells were different between patients with high and low METTL1 expression. Further, activated CD8 T-cells, activated CD4 T-cells, memory B-cells were correlated with METTL1. The genes of LAMP3, CD83, PDCD1LG2, IGKVD3D-20, IGKV5-2, IGKV2D-30, IGLV3-19 and IGLV4-60 were identified as candidate targets that were correlated with immune cell proportion. Moreover, LAMP3, CD83, and PDCD1LG2 expression were of diagnostic value in SLE as indicated by ROC analysis. Our findings suggested that METTL1 and its candidate targets LAMP3, CD83, PDCD1LG2 may be used for diagnosing SLE and could be explored for developing targeted molecular therapy for SLE.

Fragility fractures in lupus patients: Associated factors and comparison of four fracture risk assessment tools.

Osteoporosis (OP) and fragility fractures (FF) are common comorbidities in patients with systemic lupus erythematosus (SLE). This study aimed to (1) assess the prevalence of these conditions in a cohort of SLE patients (2) evaluate the risk factors associated with FF, and (3) compare the accuracy of four different FF risk assessment algorithms to determine which performs better in this specific rheumatologic population. We conducted a cross-sectional study with SLE women who underwent bone mineral density assessment by dual-energy X-ray absorptiometry (DEXA) within 3months of their last visit. Conventional radiology methods were used to evaluate the presence of FF. The 10-year risk of osteoporotic fractures was estimated using four tools: DeFRA, FRAX (adjusted for GC dosage), GARVAN, and QFracture. The comparison of these computational tools was analyzed by the area under the receiver operating characteristic (ROC) curves. We analyzed 86 SLE patients with a median age of 56years (IQR 12.1) and a median age at diagnosis of 34years (IQR 17.2). The median T-score values at the femoral neck and lumbar spine were -1.6 (IQR 0.9) and -1.7 (IQR 1.1), respectively. Of the patients, 33 (38.4%) had OP, with 13 patients (15.1%) experiencing FF. Univariate analysis showed that the presence of FF was associated with thrombocytopenia (p = .01), hemolytic anemia (p = .0001), and the intake of cyclosporine A (p = .002), cyclophosphamide (p = .006), and rituximab (p = .001). The median 10-year risk of major FF for the four calculation tools were as follows: DeFRA 9.85 (IQR 8.6); FRAX GC 8.8 (IQR11.7); GARVAN 12 (IQR 8.2); QFracture 4.1 (IQR 5.8). We observed a significant correlation among all instruments evaluated (p < .0001); in particular, the best correlation was recorded between the FRAX GC and the DeFRA (r = 0.85). DeFRA was the best tool for this population with an AUC of 0.94 (p < .0001, CI 0.88-1). OP is a common comorbidity in SLE patients, even in younger patients. FF appears to be more frequent in patients with hematologic involvement. The comparison of the four algorithms shows that DeFRA is the most accurate tool and should be applied to SLE patients.

P165 The incidence of cancer in SLE patients receiving biologic therapy: Results from the British Isles Lupus Assessment Group Biologics Registry (BILAG-BR)

Abstract Background/Aims Patients with systemic lupus erythematosus (SLE) are known to have an increased risk of certain cancers, such as lymphoma, compared to the general population. We aimed to characterise the incidence of cancers in patients with moderate-severe SLE receiving biologic and standard of care (SoC) therapies. Methods The BILAG Biologics Registry (BILAG-BR) is a large prospective observational register of patients with SLE. Participants receiving rituximab, belimumab and SoC therapies from 2010-2021 were included. Data relating to malignancy were collected from study centres and the UK national cancer register. Overall cancer risk was assessed using a Cox proportional hazards model in Stata V14. Results There were 114 previous cancer diagnoses in 108 patients recorded. The most common cancer sites were cervical (43/114), non-melanoma skin cancer (20), breast (15) and lymphoma (13). All cervical neoplasms were carcinoma in situ. Five patients had more than one cancer diagnosis recorded; three had &amp;gt;1 non-melanoma skin cancer and two individuals had unrelated malignancies. During follow-up, (1437 patients with 5,738 person years [pys]), 33 incident cancers occurred in 32 individuals at a median of 477 (IQR 218-1265) days after registration. Incidence rates were 5.9 (95% CI 3.9-8.8) in rituximab, 7.8 (2.5-24.2) in belimumab and 4.16 (1.7-10.0) per 1,000 pys in the SoC group. Using rituximab as the comparator, the age and gender adjusted hazard ratio (HR) was 1.62 (0.48-5.52) for belimumab and 0.63 (0.24-1.65) for the SoC group. Patients who developed an incident cancer were older at registration (HR 1.07 [1.04-1.09] per year) and more likely to be of male sex (HR 2.95 [1.31-6.57]). Caucasian ethnicity was associated with increased risk in univariate analysis (HR 4.25 [1.46-12.32]), but not after adjusting for age and sex (HR 2.60 [0.86-7.83]). There were 6 cancer-related deaths which all occurred in the rituximab group a median of 2.3 (IQR 1.4-3.2) years from registration. Conclusion Although overall cancer numbers are low, the findings of this study are reassuring. The incidence of cancer in this cohort of SLE patients with moderate-to-severe disease appears to be broadly similar between those on biologic and standard of care therapies. Disclosure M. Rodziewicz: Grants/research support; North West England MRC Fellowship Scheme in Clinical Pharmacology and Therapeutics. Award Ref. MR/N025989/1, UCB. S. Dyball: Grants/research support; North West England Medical Research Council Fellowship Scheme in Clinical Pharmacology and Therapeutics. Award Ref. MR/N025989/1, UCB, Eli Lilly. E. Sutton: None. B. Parker: Honoraria; Fresenius-Kabi, AbbVie. Member of speakers’ bureau; Eli Lilly, Roche. Grants/research support; Genzyme/Sanofi, GSK. I.N. Bruce: Consultancies; AstraZeneca, Eli Lilly, ILTOO, GSK, Aurinia. Member of speakers’ bureau; GSK, UCB, AstraZeneca. Grants/research support; GSK, Roche, Janssen.

Risk of End-Stage Renal Disease in Patients With Systemic Lupus Erythematosus and Diabetes Mellitus: A Danish Nationwide Cohort Study.

The risk of end-stage renal disease (ESRD) is increased in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine whether diabetes mellitus (DM) increases ESRD risk in a large inception cohort of SLE patients. By means of the Danish National Patient Registry, we identified 3,178 adult patients diagnosed as having SLE between January 1, 1996, and July 31, 2018. DM was defined as the date of first hospital contact for DM or date of a first prescription of an antidiabetic drug. ESRD was defined as first registration of dialysis, renal transplant, or terminal renal insufficiency in the Danish National Patient Registry. ESRD incidence was compared between SLE patients with DM (SLE-DM) and those without DM (SLE-non-DM). Hazard ratios (HRs), adjusted for sex, age, educational level, and occupational status at baseline were calculated for sex, age, educational level, and hypertension (at baseline or during follow-up) strata. The overall hazard ratio (HR) was also adjusted for hypertension. The SLE-DM group included 290 patients, of whom 77% were female, compared with 85% of the 2,859 patients in the SLE-non-DM group. SLE-DM patients had a 3 times higher risk of ESRD compared with SLE-non-DM patients (multivariable-adjusted HR 3.3 [95% confidence interval 1.8-6.1]). In stratified multivariable-adjusted analyses, DM increased the rate of ESRD in women and men, patients ≥50 years old at baseline, those with low educational level at baseline, and those with concomitant hypertension. Our findings indicate that SLE patients with DM have a markedly higher risk of developing ESRD compared with SLE patients without DM.

A Flare Risk Index Informed by Select Immune Mediators in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is marked by immune dysregulation linked to varied clinical disease activity. Using a unique longitudinal cohort of SLE patients, this study sought to identify optimal immune mediators informing an empirically refined flare risk index (FRI) reflecting altered immunity prior to clinical disease flare. Thirty-seven SLE-associated plasma mediators were evaluated by microfluidic immunoassay in 46 samples obtained in SLE patients with an imminent clinical disease flare (preflare) and 53 samples obtained in SLE patients without a flare over a corresponding period (pre-nonflare). SLE patients were selected from a unique longitudinal cohort of 106 patients with classified SLE (meeting the American College of Rheumatology 1997 revised criteria for SLE or the Systemic Lupus International Collaborating Clinics 2012 revised criteria for SLE). Autoantibody specificities, hybrid SLE Disease Activity Index (hSLEDAI) scores, clinical features, and medication usage were also compared at preflare (mean ± SD 111 ± 47 days prior to flare) versus pre-nonflare (99 ± 21 days prior to nonflare) time points. Variable importance was determined by random forest analysis with logistic regression subsequently applied to determine the optimal number and type of analytes informing a refined FRI. Preflare versus pre-nonflare differences were not associated with demographics, autoantibody specificities, hSLEDAI scores, clinical features, nor medication usage. Forward selection and backward elimination of mediators ranked by variable importance resulted in 17 plasma mediator candidates differentiating preflare from pre-nonflare visits. A final combination of 11 mediators best informed a newly refined FRI, which achieved a maximum sensitivity of 97% and maximum specificity of 98% after applying decision curve analysis to define low, medium, and high FRI scores. We verified altered immune mediators associated with imminent disease flare, and a subset of these mediators improved the FRI to identify SLE patients at risk of imminent flare. This molecularly informed, proactive management approach could be critical in prospective clinical trials and the clinical management of lupus.

Co-occurrence of familial Mediterranean fever with systemic lupus erythematosus in South Asian population

Background and objectiveFamilial Mediterranean fever (FMF) and systemic lupus erythematosus (SLE) are autosomal recessive auto-inflammatory diseases, triggered by FMF-associated gene mutations and auto-antigens. The literature on the co-occurrence of these two disorders is limited to case reports and their correlation is considered rare. We investigated the proportion of FMF among SLE patients when compared with a healthy adult cohort in South Asia. MethodsFor this observational study, data from our institutional database were collected for the patients diagnosed with SLE. The control group was randomly selected from the database and were age- matched for SLE. The overall proportion of FMF among patients with and without SLE was considered. Student's t-test, Chi-square, and ANOVA were used for univariate analysis. ResultsThe study population included 3623 SLE patients and 14,492 controls. In the SLE group, there was a significantly higher proportion of FMF patients compared with the non-SLE group (1.29% vs. 0.79% respectively; p=0.015). SLE was prevalent in Pashtun's (50%) in the middle socioeconomic group while FMF was dominant in Punjabi's and Sindhi's (53%) in the low socioeconomic class. ConclusionThis investigation demonstrates that FMF is more prevalent in a South-Asian population cohort of SLE patients.

Salivary IgA subtypes as novel disease biomarkers in systemic lupus erythematosus.

Immunoglobulin A (IgA) is the main antibody isotype in body fluids such as tears, intestinal mucous, colostrum, and saliva. There are two subtypes of IgA in humans: IgA1, mainly present in blood and mucosal sites, and IgA2, preferentially expressed in mucosal sites like the colon. In clinical practice, immunoglobulins are typically measured in venous or capillary blood; however, alternative samples, including saliva, are now being considered, given their non-invasive and easy collection nature. Several autoimmune diseases have been related to diverse abnormalities in oral mucosal immunity, such as rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus (SLE). We decided to evaluate the levels of both IgA subtypes in the saliva of SLE patients. A light chain capture-based ELISA measured specific IgA1 and IgA2 levels in a cohort of SLE patients compared with age and gender-matched healthy volunteers. Surprisingly, our results indicated that in the saliva of SLE patients, total IgA and IgA1 subtype were significantly elevated; we also found that salivary IgA levels, particularly IgA2, positively correlate with anti-dsDNA IgG antibody titers. Strikingly, we also detected the presence of salivary anti-nucleosome IgA antibodies in SLE patients, a feature not previously reported elsewhere. According to our results and upon necessary validation, IgA characterization in saliva could represent a potentially helpful tool in the clinical care of SLE patients with the advantage of being a more straightforward, faster, and safer method than manipulating blood samples.

Features of clinical manifestations, course, outcomes and health related quality of life in patients with systemic lupus erythematosus in the Republic of Kazakhstan

Objective – to evaluate the features of clinical manifestations, course, outcomes and quality of life related to health in patients with systemic lupus erythematosus in the Republic of Kazakhstan.Patients and methods. The study included 102 patients with systemic lupus erythematosus (SLE) with a reliable diagnosis according to SLICC (2012). Disease activity was assessed by the SLEDAI 2K index, organ damage (IOD) by SLICC/ACR (2000). Statistical processing was carried out using SPSS 13 software (IBM Corp., USA). Variables with a parametric distribution are presented as М±SD, nonparametric – as a median (Me) [25th; 75th percentile].Results and discussion. The cohort was dominated by female patients (98%), Asians (83.33%), young patients (33.85±10.58 years) with a disease duration of 5 [2; 9] years with high (30.8%) and very high (39.2%) degree of activity (SLEDAI-2K – 17.64±8.80 points). The debut of the disease was in 18.6% of patients in adolescence, it was characterized by an unfavorable course. Clinical manifestations of the disease: skin lesions (acute active and chronic forms) (98%), joints (79.4%), non-scarring alopecia (75.5%), neuropsychiatric disorders (49%), mucous membranes (46.1%), hematological (54.9%) and immunological disorders (100%). IOD: low – in 20.6%, medium – in 59.8%, high – in 9.8% of patients, 0 – in 9.8%, Risk factors for poor outcome were in 93.1% of patients. Assessment of health-related quality of life (HRQOL) in SLE patients showed a significant decrease on all scales. Correction of the treatment program, taking into account the factors of adverse outcome (FRNI), consisted in strengthening therapy with the inclusion of genetically engineered biological drugs (GEBP).Conclusion. SLE is a socially significant disease in Kazakhstan with a high incidence rate (101%) over 10 years (2009–2018). The cohort of SLE patients is dominated by young people, females. The duration of the disease is up to 5 years with a delayed verification of the diagnosis of SLE. Organ damage is already in the onset of the disease and the presence of FRNI of the disease in 93.1% of patients, which indicates the severity of the course, which requires early diagnosis and active involvement of pathogenetic treatment, including GEBD.

Hydroxychloroquine Use and Cardiovascular Events Among Patients With Systemic Lupus Erythematosus and Rheumatoid Arthritis.

We evaluated the potential temporal association between hydroxychloroquine (HCQ) use and cardiovascular (CV) events among patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). We conducted a nested case-control study within inception cohorts of SLE and RA patients using administrative health databases including the entire population of British Columbia, Canada. We identified cases with incident CV events, including myocardial infarction (MI), stroke, or venous thromboembolism (VTE). We matched each case with up to 3 controls on age, sex, and rheumatic disease. HCQ exposure was categorized by the time between the last HCQ prescription date covered and the index date as current use, recent use, remote use, or never used. We used conditional logistic regression to assess the association between HCQ exposure and CV events, using remote use as the reference group. We identified 10,268 cases and 29,969 controls. Adjusted conditional odd ratios (cORs) and 95% confidence intervals (95% CIs) for current HCQ use relative to remote use were 0.86 (0.77-0.97) for combined CV events, 0.88 (0.74-1.05) for MI, 0.87 (0.74-1.03) for stroke, and 0.74 (0.59-0.94) for VTE. Recent HCQ users and nonusers had similar odds of combined CV events as remote users (cORs 0.93, 95% CI 0.77-1.13 and 0.96, 95% CI 0.88-1.04, respectively). In this nested case-control study of patients with SLE and RA, we found a reduced risk of overall CV events associated with current HCQ use, including reductions in VTE and trends toward reductions in MI and stroke. These findings suggest a possible cardiovascular preventative benefit of HCQ use.

Evaluation of Subclinical Retinal Disease in Patients Affected by Systemic Lupus Erythematosus with No Evidence of Ocular Involvement-An Optical Coherence Tomography Angiography Original Study.

Lupus retinopathy is the second most common eye involvement in systemic lupus erythematosus (SLE), associated with significant visual deterioration and well-known negative prognostic factor for survival. Ocular manifestation in SLE, relating the retina, ranges from asymptomatic vascular involvement to vision devastating vascular occlusions. Subclinical microvascular changes are undetectable in slit lamp examination, hence are underdiagnosed. Optical coherence tomography angiography (OCTA) is a novel, easy to interpret and non-invasive technique that allows retinal vessels visualization. OCTA simplifies clinical approach and measures the severity of decreased perfusion. The aim of the study was to demonstrate the retinal vascularization in a subclinical stage of ocular involvement in a cohort of SLE patients. Thirty-three patients (57 eyes) diagnosed with SLE were enrolled into the study group and 31 healthy individuals (56 eyes) into the control group. Vessel density reduction in parafovea, inferior and nasal quadrants of superficial retinal capillary plexus in a cohort of SLE patients was found. Among study group kidney involvement was associated with further microvasculature reduction. Knowing that retinal involvement may precede other organs impairment, early detection of retinal impairment and use of OCTA as a screening modality, may decrease overall disease morbidity.

Comparison of two anti-histones antibodies commercial assays in an immunology laboratory and systemic lupus erythematosus

BackgroundAnti-histones antibodies (AHAs) are antibodies directed against histone proteins – structural proteins that provides scaffolding for DNA to be wrapped around. AHAs, measured in the serum, are diagnostically helpful in cases of systemic lupus erythematosus (SLE) and drug-induced lupus erythematosus (DILE). In the diagnostic laboratory, they may be measured by enzyme-linked immune-sorbent assay (ELISA) or line immunoassays (LIA); however, the performance of these have never been directly compared in the literature. MethodsWe evaluated a commonly used commercial ELISA and LIA to compare the performance in our immunology laboratory. Retrospective and prospective analyses were undertaken over a 5.5-year period. We also examined their performance in the model disease of SLE and compared their performance to disease activity and the main clinical features. ResultsOne hundred and thirty-five patients were evaluated including 65 SLE patients. Based on the quantitative cut-offs, there was only moderate agreement between the two assays (κ = 0.444). Both assays only had modest agreement with the clinical situation of the evaluated patients. When considered within the SLE context, both assays were moderately correlated with disease activity. Positive AHAs by ELISA were associated with SLE cytopaenias, and both ELISA and LIA correlated with positive anti-double stranded DNA. ConclusionsModerate agreement analytically were seen between ELISA and LIA methods in a general laboratory cohort. Both assays were comparable in their diagnostic performance. ELISA detection of AHAs appears to have some clinical use in our cohort of SLE patients. Future studies are required to explore the clinical utility of AHAs in SLE and other disorders.

Rates of Pneumocystis jirovecii pneumonia and prophylaxis prescribing patterns in a large electronic health record cohort of patients with systemic lupus erythematosus

Objective No guidelines exist for Pneumocystis jirovecii pneumonia (PJP) prophylaxis in patients with systemic lupus erythematosus (SLE). Limited data are available on incidence of PJP infection and use of PJP prophylaxis. Using a real-world, electronic health record (EHR) cohort, we investigated the frequency of PJP infections as well as patient and provider factors that impacted use and type of PJP prophylaxis.Methods In a large, de-identified EHR, we identified possible SLE patients using a previously validated algorithm. PJP ICD-9 or ICD-10-CM billing codes and PJP keywords were used to identify possible PJP cases within this SLE cohort. We assessed for PJP prophylaxis prescribing in all SLE patients using keywords and reviewing medication lists for prophylactic agents. Chart review was used to confirm cases of SLE, PJP, and PJP prophylaxis and to obtain data on demographics, comorbidities, and immunosuppressants.Results Of 977 SLE patients, there were only four with confirmed PJP infection. Two of these patients had concurrent Acquired Immunodeficiency Syndrome, and none were on prophylaxis. Of 977 SLE patients, 132 (14%) were prescribed PJP prophylaxis. Of 617 SLE patients ever prescribed immunosuppressants, 128 (21%) were prescribed PJP prophylaxis. Sulfonamides were the most common prophylaxis prescribed (69%), and possible adverse events were documented in 22 out of 117 instances of being placed on a sulfonamide. Patients of younger age, Black race, nephritis, and renal transplant, and on chronic glucocorticoids were all more likely to have PJP prophylaxis prescribed. Patients who were on transplant induction medications, calcineurin/mTOR inhibitors, cyclophosphamide, and mycophenolate mofetil all were more likely to be prescribed PJP prophylaxis compared to other immunosuppressants.Conclusion PJP is a rare diagnosis among SLE patients, and prior studies may even overestimate its prevalence. PJP prophylaxis was less common in our cohort than previously described. Adverse events related to sulfonamides used for PJP prophylaxis were relatively rare with lower rates than previously reported. Our study demonstrates real-world PJP prophylaxis prescribing patterns in a large cohort of SLE patients.

CARDIOVASCULAR RISK STATUS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: COMPARISON OF FRAMINGHAM, ACC/AHA, AND QRISK3 SCORES

CARDIOVASCULAR RISK STATUS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: COMPARISON OF FRAMINGHAM, ACC/AHA, AND QRISK3 SCORES

Neuropsychiatric manifestations and their attribution to systemic lupus erythematosus: a retrospective single-center study in a Polish population.

Neuropsychiatric (NP) manifestations occur in patients with systemic lupus erythematosus (SLE), and it is challenging to distinguish these manifestations from other neuropsychiatric conditions. We aimed to assess the prevalence of primary neuropsychiatric SLE (NPSLE) in a Polish cohort of SLE patients. This retrospective, cross‑sectional study evaluated 164 patients with SLE. NP manifestations were attributed to SLE using the Italian model. Demographic and clinical data, including disease activity (measured by the Systemic Lupus Erythematosus Disease Activity Index version 2000 [SLEDAI‑2K] and the Physician Global Assessment) and organ damage (measured by the Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index), were obtained in patients with and without NP manifestations attributed to SLE. The final analysis set included 143 patients, 34 of whom (23.8%) had NP manifestations attributed to SLE. The age of the patients with NPSLE and the age of disease onset were significantly lower in comparison with those without NP symptoms attributed to SLE (median [interquartile range], 38 [29-45] vs 45 [32-55] years; P = 0.009, and 35 [24-38] vs 40 [25-48] years; P = 0.03, respectively). The disease activity and proportion of patients with active disease (SLEDAI‑2K ≥6) was significantly higher in the NPSLE patients than in those without NP symptoms attributed to SLE (P <0.005; 100% vs 85.3%; P = 0.01, respectively). NP manifestations in the central nervous system were the most frequent (91.5%). In the patients with NPSLE, cerebrovascular disease, seizures, cognitive dysfunction, psychosis, and cranial neuropathy occurred most often. NP manifestations occurred mainly in young patients with high disease activity. Cerebrovascular disease, seizures, psychosis, cognitive dysfunction, and cranial neuropathy were the most frequent manifestations of NPSLE.

Plasmablast-like Phenotype Among Antigen-Experienced CXCR5-CD19low B Cells in Systemic Lupus Erythematosus.

Altered composition of the B cell compartment in the pathogenesis of systemic lupus erythematosus (SLE) is characterized by expanded plasmablast and IgD-CD27- double-negative B cell populations. Previous studies showed that double-negative B cells represent a heterogeneous subset, and further characterization is needed. We analyzed 2 independent cohorts of healthy donors and SLE patients, using a combined approach of flow cytometry (for 16 healthy donors and 28 SLE patients) and mass cytometry (for 18 healthy donors and 24 SLE patients) and targeted RNA-Seq analysis. To compare B cell subset formation during the acute immune response versus that during autoimmune disease, we investigated healthy donors at various time points after receipt of the BNT162b2 messenger RNA COVID-19 vaccine and patients with acute SARS-CoV-2 infection, using flow cytometry. We found that IgD-CD27+ switched and atypical IgD-CD27- memory B cells, the levels of which were increased in SLE patients, represented heterogeneous populations composed of 3 different subsets each. CXCR5+CD19intermediate , CXCR5-CD19high , and CXCR5-CD19low populations were found in the switched memory and double-negative compartments, suggesting the relatedness of IgD-CD27+ and IgD-CD27- B cells. We characterized a hitherto unknown and antigen-experienced CXCR5-CD19low subset that was enhanced in SLE patients, had a plasmablast phenotype with diminished B cell receptor responsiveness, and expressed CD38, CD95, CD71, PRDM1, XBP1, and IRF4. Levels of CXCR5-CD19low subsets were increased and correlated with plasmablast frequencies in SLE patients and in healthy donors who received BNT162b2, suggesting their interrelationship and contribution to plasmacytosis. The detection of CXCR5-CD19low B cells among both CD27+ and CD27- populations calls into question the role of CD27 as a reliable marker of B cell differentiation. Our data suggest that CXCR5-CD19low B cells are precursors of plasmablasts. Thus, cotargeting this subset may have therapeutic value in SLE.

Differential impact of disease activity and damage on health-related quality of life in patients with systemic lupus erythematosus.

To study the association between disease activity, disease-related organ damage and health-related quality of life (HRQoL) among Asian patients with systemic lupus erythematosus (SLE). We prospectively recruited adult SLE patients from a single tertiary center and followed them three-monthly. We recorded the SLE Disease Activity Index 2000 (SLEDAI-2K) at each visit. SLICC-ACR damage index (SDI) and HRQoL (Medical Outcomes Survey Short Form 36 (SF-36)) were recorded annually. We evaluated the association between SLEDAI-2K and SDI with SF-36 physical (PCS) and mental (MCS) component scores using linear mixed effect models. We studied 198 patients, comprising Chinese, Malays and Indians. The mean (SD) age at enrollment was 47.1 (12.5) years. The baseline median (IQR) SLEDAI-2k was 2 (0-4). While the mean PCS improved significantly in the second and third year, MCS was unchanged. In the multivariable mixed model analysis, SDI, but not SLEDAI-2k, was significantly associated with poorer PCS (estimate of coefficient (SE) -0.81 (0.29), p < .01). Conversely, SLEDAI-2k, but not SDI, was negatively associated with MCS (estimate of coefficient (SE) -0.36 (0.17), p = .04). In this cohort of multi-ethnic Asian SLE patients, disease activity is associated with poorer mental, but not physical, HRQoL; whereas disease-related damage is associated with poorer physical, but not mental HRQoL. Our findings suggest a need to differentially approach the impaired HRQoL in SLE patients at different phases of disease; possibly by treating disease activity in patients with impaired mental HRQoL and addressing disease-related damage in patients with impaired physical functioning.