Gender differences in disease activity and clinical features in newly diagnosed systemic lupus erythematosus patients

Objective.To compare clinical features and mortality between childhood-onset systemic lupus erythematosus (cSLE) and adult-onset SLE (aSLE) in a prospective single-center cohort.Methods.A total of 1112 patients with SLE (133 cSLE and 979 aSLE) were enrolled and followed from 1998 to 2012. The 2 groups were compared regarding American College of Rheumatology (ACR) classification criteria for SLE, autoantibodies, disease activity measured by the Adjusted Mean SLE Disease Activity Index (AMS), damage measured by the Systemic Lupus International Collaborating Clinics/ACR Damage Index (SDI), and medication. The standardized mortality ratio (SMR) was calculated. Predictors of mortality in SLE were evaluated using Cox proportional hazard models.Results.After a mean followup of 7.6 years, patients with cSLE had a higher number of cumulative ACR criteria and a higher AMS (p < 0.001 each), but there was no difference in SDI (p = 0.797). Immunosuppressants were used more frequently by patients with cSLE (p < 0.001). The SMR of cSLE was 18.8 (95% CI 8.6–35.6), significantly higher than that of aSLE (2.9, 95% CI 2.1–3.9). We found cSLE to be an independent predictor of mortality (HR 3.6, p = 0.008). Moreover, presence of hemolytic anemia (7.2, p = 0.034) and antiphospholipid antibody (aPL; 3.8, p = 0.041) increased the magnitude of risk of early mortality more in the patients with cSLE than in those with aSLE.Conclusion.The clinical course of cSLE as measured by number of clinical manifestations and disease activity is worse than that of aSLE. Also, cSLE patients with hemolytic anemia and aPL are at greater risk of death than patients with aSLE who have those features.

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Clinical Features and Prognosis of Late-onset Systemic Lupus Erythematosus: Results from the 1000 Faces of Lupus Study

The Journal of Rheumatology ◽

10.3899/jrheum.080957 ◽

2009 ◽

Vol 37 (1) ◽

pp. 38-44 ◽

Cited By ~ 64

Author(s):

SHELIZA LALANI ◽

JANET POPE ◽

FAYE de LEON ◽

CHRISTINE PESCHKEN

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Clinical Features ◽

Lupus Erythematosus ◽

Late Onset ◽

Control Group ◽

Systemic Lupus ◽

Damage Accrual ◽

Onset Group ◽

Onset Systemic Lupus Erythematosus

Objective.There is controversy whether older-onset systemic lupus erythematosus (SLE) is associated with a different, more benign disease course than in younger-onset SLE. Our objective was to characterize the clinical features and prognosis of late-onset SLE in a large, multicenter cohort.Methods.We studied adult-onset lupus in the 1000 Canadian Faces of Lupus cohort (n = 1528) of whom 10.5% had onset at age ≥ 50 years versus a control group with onset at < 50 years.Results.Disease duration was different in early- and late-onset groups (15 yrs in early vs 9.3 yrs in late; p < 0.001). Caucasians were represented more in the later-onset SLE group (55.6% vs 74.5%), while Asians and Blacks were more prevalent in the younger group. Younger-onset SLE subjects fulfilled more American College of Rheumatology criteria for SLE (< 50 yrs: 5.98 ± 1.68; ≥ 50 yrs: 5.24 ± 1.44; p < 0.0001). Despite an equal prevalence of anti-dsDNA, the younger-onset group more often had positive anti-Smith autoantibody, ribonucleoprotein, and hypocomplementemia, and more nephritis, rash, and cytopenias than the older-onset group. However, disease activity and damage accrual were higher in the older-onset group. The older patients received less prednisone and immunosuppressives (current and ever-use). As expected, comorbidity was higher in the older-onset SLE group.Conclusion.This study suggests that older age-onset SLE is not benign. There may be an interaction between lupus and age in which, although there is less lupus nephritis in the elderly, more disease activity and damage are present.

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Retinopathy in newly-diagnosed systemic lupus erythematosus: should we screen for ocular involvement?

BMC Rheumatology ◽

10.1186/s41927-021-00203-5 ◽

2021 ◽

Vol 5 (1) ◽

Author(s):

Hamidreza Bashiri ◽

Nooshin Karimi ◽

Shayan Mostafaei ◽

Azarakhsh Baghdadi ◽

Mohammad Nejadhosseinian ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

High Rate ◽

Common Finding ◽

Ocular Involvement ◽

Newly Diagnosed ◽

Systemic Lupus ◽

Laboratory Test Results

Abstract Background Ocular manifestations are common in systemic lupus erythematosus (SLE). Retinopathy has previously been linked to disease severity and might have a significant impact on the patient’s quality of life and has also been associated with a poor prognosis in SLE. This study aimed to determine the prevalence of retinopathy among patients who are newly diagnosed with SLE. Methods In a cross-sectional study, patients diagnosed with SLE at a tertiary referral clinic were assessed for inclusion between March 2016 and March 2017. Patients who had received treatment for SLE at any time were excluded, as well as patients with hypertension, diabetes mellitus, and coagulopathy. Clinical findings and laboratory test results were recorded, and patients were examined by an ophthalmologist for evidence of retinal pathologies. SLE disease activity index was also calculated for all patients. Results With 114 patients included in the final analysis, we found a prevalence of 15.8% for retinopathy among newly-diagnosed SLE patients. Cotton-wool spots were the most common finding (78%). Patients with retinopathy had significantly lower hemoglobin levels, C3 and C4 concentrations, and higher ANA and Anti-dsDNA levels. Also, patients with retinopathy had a significantly higher SLE DAI score. Conclusions We found a relatively high rate of retinopathy in SLE patients at the time of their initial diagnosis. Our findings suggest that retinopathy is an early manifestation of the disease. Ophthalmologic screening might be considered for SLE patients at the time of diagnosis, especially for those with severe disease. We also encourage researchers to further evaluate the correlation between retinopathy and disease activity, and the prognosis of ocular involvement.

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Altered Profile of Fecal Microbiota in Newly Diagnosed Systemic Lupus Erythematosus Egyptian Patients

International Journal of Microbiology ◽

10.1155/2021/9934533 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Marian A. Gerges ◽

Noura E. Esmaeel ◽

Wafaa K. Makram ◽

Doaa M. Sharaf ◽

Manar G. Gebriel

Keyword(s):

Systemic Lupus Erythematosus ◽

Gut Microbiota ◽

Disease Activity ◽

Lupus Erythematosus ◽

Healthy Subjects ◽

Fecal Microbiota ◽

Healthy Controls ◽

Newly Diagnosed ◽

Systemic Lupus ◽

Egyptian Patients

Background. Dysbiosis of gut microbiota could promote autoimmune disorders including systemic lupus erythematosus (SLE). Clarifying this point would be of great importance in understanding the pathogenesis and hence the development of new strategies for SLE treatment. Aim. This study aimed to determine the fecal microbiota profile in newly diagnosed SLE patients compared to healthy subjects and to investigate the correlation of this profile with disease activity. Methods. Newly diagnosed SLE patients who fulfilled at least four of the American College of Rheumatology (ACR) criteria were enrolled during the study period. Patients with lupus were matched to healthy subjects. SLE activity was evaluated using the Systemic Lupus Disease Activity Index (SLEDAI-2K). Fresh fecal samples were collected from each subject. Genomic DNA was extracted from fecal samples. Quantitative real-time PCR was applied for quantitation of Firmicutes phylum, Bacteroidetes phylum, and Lactobacillus genus in comparison to the total fecal microbiota. Results of patients’ samples were compared to those of healthy subjects and were correlated to patients’ SLEDAI-2K score. Results. Twenty SLE patients’ samples were compared with 20 control samples. There was a significant alteration in SLE patients’ gut microbiota. A significantly lower ( p ≤ 0.001 ) Firmicutes/Bacteroidetes (F/B) ratio in SLE patients (mean ratio: 0.66%) compared to healthy subjects (mean ratio: 1.79%) was found. Lactobacillus showed a significant decrease in SLE patients ( p = 0.006 ) in comparison to healthy controls. An inverse significant correlation between SLEDAI-2K scores for disease activity and F/B ratio (r = −0.451; p = 0.04 ) was found. However, an inverse nonsignificant correlation between SLEDAI-2K scores for disease activity and Lactobacillus (r = −0.155; p = 0.51 ) was detected. Conclusion. Compared to healthy controls, recently diagnosed SLE Egyptian patients have an altered fecal microbiota profile with significant lowering of both F/B ratio and Lactobacillus abundance, which is weakly correlated with disease activity.

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FRI0183 DISTINCTIVE TRAITS OF MYOCARDIAL INFLAMMATION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: A MULTICENTRE STUDY

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4653 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 675.2-675

Author(s):

G. A. Ramirez ◽

M. Gerosa ◽

G. De Luca ◽

L. Beretta ◽

S. Sala ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Clinical Features ◽

Lupus Erythematosus ◽

Early Onset ◽

Disease Duration ◽

Late Onset ◽

Myocardial Inflammation ◽

Systemic Lupus ◽

Research Support

Background:Myocarditis is an infrequent but potentially life-threatening inflammatory disorder and might be part of the spectrum of systemic lupus erythematosus (SLE). Little is known about the clinical and histologic features of myocarditis in SLE, especially compared to other forms of myocarditis.Objectives:to test for potential distinctive traits among myocarditis in SLE (MyoSLE), SLE without myocarditis (OnlySLE) and myocarditis without SLE (OnlyMyo)Methods:Patients with MyoSLE were identified from three centres and compared with 231 cross-sectionally enrolled patients with OnlySLE and 87 patients with OnlyMyo. MyoSLE patients were split into two groups based on myocarditis onset within (early onset) vs after (late onset) the first year from SLE diagnosis. OnlySLE patients were dichotomised in the same way based on disease duration at time of enrolment. Demographics and general clinical features were collected retrospectively. SLE disease activity index 2000 (SLEDAI-2K), SLE International Collaborating Clinics/American College of Rheumatology damage index (SDI), clinical and laboratory features were collected at time of myocarditis onset in MyoSLE and at enrolment in OnlySLE. Quantitative data are expressed as median [interquartile range].Results:Fourteen MyoSLE patients were identified, 50% with early onset. Women were equally frequent among MyoSLE (71%) and OnlySLE patients (87%) and less frequent in the OnlyMyo group (43%; p<0.001). Age was comparable among groups. Clinical features at presentation, including left ventricular ejection fraction, were similar between MyoSLE and OnlyMyo, although the former had higher levels of pro-brain natriuretic peptide (1.1 [0.4-1.8] vs 0.1 [0.1-0.5] ng/ml; p=0.004). Patients with MyoSLE also had a lower frequency of left ventricle lateral wall involvement (36 vs 68%; p=0.035) and of oedema (20 vs 71%; p=0.036) and necrosis (0 vs 64%; p=0.009) at biopsy. Antiphospholipid antibodies (aPL) were more frequent in MyoSLE (57%) compared to both OnlyMyo (16%; p=0.003) and OnlySLE (28%; p=0.031). Compared to OnlySLE, patients with MyoSLE also had a higher prevalence of aPL-syndrome (APS: 36 vs 7%; p=0.003), neuropsychiatric (NPSLE: 43 vs 19%; p=0.039) and gastrointestinal manifestations (21 vs 5%; p=0.045). Early and late onset patients had similar demographics and clinical features and did not differ from patients with OnlySLE with similar disease duration in terms of SLEDAI-2K and SDI. Late onset MyoSLE patients had a higher prevalence of NPSLE (57 vs 18%; p=0.026) and APS (57 vs 7%; p=0.001) and higher C-reactive protein levels (6 [2-12] vs 1[0-4] mg/l; p=0.024) compared to OnlySLE patients with the same disease duration.Conclusion:Demographics of patients with MyoSLE are more similar to patients with OnlySLE than to OnlyMyo patients. MyoSLE might have distinct histological and pathogenic features compared to OnlyMyo. Patients with MyoSLE show similar patterns of disease activity and accrued damage at time of myocarditis onset compared to patients with OnlySLE with the same disease duration but might diverge later on in SLE course. aPL are frequent in MyoSLE and might both contribute to the pathogenesis of myocardial inflammation and account for the high prevalence of NPSLE and APS, especially in late onset cases.References:[1]Gartshteyn Y et al., Lupus, 2020[2]Thomas G et al., J Rheumatol, 2017[3]Peretto G et al., Int J Cardiol, 2019[4]McDonnell T et al., Blood Rev, 2019Disclosure of Interests:Giuseppe Alvise Ramirez: None declared, Maria Gerosa: None declared, Giacomo De Luca Speakers bureau: SOBI, Novartis, Celgene, Pfizer, MSD, Lorenzo Beretta Grant/research support from: Pfizer, Simone Sala: None declared, Giovanni Peretto: None declared, Luca Moroni: None declared, Francesca Mastropaolo: None declared, adriana cariddi: None declared, Silvia Sartorelli: None declared, Corrado Campochiaro Speakers bureau: Novartis, Pfizer, Roche, GSK, SOBI, Enrica Bozzolo: None declared, Roberto Caporali Consultant of: AbbVie; Gilead Sciences, Inc.; Lilly; Merck Sharp & Dohme; Celgene; Bristol-Myers Squibb; Pfizer; UCB, Speakers bureau: Abbvie; Bristol-Myers Squibb; Celgene; Lilly; Gilead Sciences, Inc; MSD; Pfizer; Roche; UCB, Lorenzo Dagna Grant/research support from: The Unit of Immunology, Rheumatology, Allergy and Rare Diseases (UnIRAR) received unresctricted research/educational grants from Abbvie, Bristol-Myers Squibb, Celgene, Janssen, Merk Sharp & Dohme, Mundipharma Pharmaceuticals, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI., Consultant of: Prof Lorenzo Dagna received consultation honoraria from Abbvie, Amgen, Biogen, Bristol-Myers Squibb, Celltrion, Novartis, Pfizer, Roche, Sanofi-Genzyme, and SOBI.

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THU0237 UNCOVERING DIFFERENCES BETWEEN THE SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) AND HEALTHY IMMUNOMES USING MULTI-PARAMETRIC INTERROGATION

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.2855 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 345.2-346

Author(s):

K. Nay Yaung ◽

J. G. Yeo ◽

M. Wasser ◽

P. Kumar ◽

S. P. Tang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Activity Index ◽

Disease Activity Index ◽

Healthy Controls ◽

Newly Diagnosed ◽

Systemic Lupus ◽

Immune System Dysfunction ◽

Holistic Understanding

Background:Systemic lupus erythematosus (SLE) is a complex, systemic autoimmune disease that interferes with the balance between regulation and immunity, resulting in immune system dysfunction. Disease course is unpredictable due to alternating remissions and flares1.Disease activity and treatment response are measured with composite scores such as the SLE Disease Activity Index (SLEDAI)2. However, disease heterogeneity can impede reliable patient assessments. Mechanistic insights into SLE are required for better assessment.Current studies are mainly descriptive, and a complex disease like SLE is best interrogated with multi-parametric, holistic approaches such as mass cytometry (CyTOF).Objectives:(1)To characterise immune signatures of newly diagnosed SLE patients and in the process:a.Study the roles of B and T cells in SLEb.Gain a holistic understanding of the adaptive immune response(2)To compare immunological profiles of newly diagnosed SLE patients with age-matched healthy controlsWe hypothesise that significant differences exist between immunomes of newly diagnosed SLE and healthy subjects.Methods:Peripheral blood mononuclear cells (PBMCs) of 5 SLE subjects (median age 125 months) were tested with CyTOF. Data was uploaded to an online analytical platform, the Extended Polydimensional Immunome Characterization (EPIC) discovery tool, for comparison with 51 age-matched controls in its database.Subsequently, normalization and FlowSOM (Flow cytometry analysis by Self-Organising Maps) clustering to 50 nodes were performed with 37 functionally and phenotypically important immune markers. The Mann-Whitney U test identified significantly different cluster frequencies.Results:Correspondence analysis comparing global differences in cluster frequencies showed segregation of SLE subjects away from healthy controls. Multiple significant differences were identified (p < 0.05). Notably, a memory CD4+CD152+PD1+T cell subset (CD4+CD152+PD1+CD45RO+CD25-FoxP3-) was enriched in SLE (median: 2.17%, interquartile range: 1.66 to 7.74% of CD45+ PBMCs) versus control (1.34%, 1.06 - 1.58%; p = 0.00267). Expression of these known checkpoint inhibitors (PD1, CD152) could be important for SLE immunopathogenesis.Secondly, the innate lymphoid cell 2 (ILC2) subset (Lin-CD7+CD25+CD127+GATA3+) was markedly depressed in SLE (0.11%, 0.1 - 0.255%) versus control (0.41%, 0.25 - 0.55%; p = 0.0293). ILC2s protect epithelial integrity; a reduction suggests impaired protective roles in SLE.Supervised cell frequencies from bivariate analysis correlate strongly with unsupervised cell frequencies, validating these results (Pearson’s correlation coefficient r = 0.9926, p < 0.001 (CD4+CD152+PD1+CD45RO+CD25-FoxP3-); r = 0.8863, p < 0.05 (ILC2)).Conclusion:With a multi-parametric, unbiased approach comparing SLE subjects to a large database of age-matched healthy controls, we identified two immune subsets of potential immunopathogenic importance. With this information, the CyTOF panel can be redesigned to probe more specifically into the SLE immunome, facilitating disease-specific interrogation.References:[1]Tsokos,G.C. (2011). Systemic lupus erythematosus.N Engl J Med365(22), 2110-2121.[2]Bombardier, C., Gladman, D.D., Urowitz, M.B., Caron, D., Chang, C.H. (1992). Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE.Arthritis Rheum35(6), 630-640.Disclosure of Interests: :None declared

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