Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis

Rheumatology ◽  
2020 ◽  
Vol 59 (6) ◽  
pp. 1416-1425
Author(s):  
Hua-Zhi Ling ◽  
Shu-Zhen Xu ◽  
Rui-Xue Leng ◽  
Jun Wu ◽  
Hai-Feng Pan ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Logistic Regression ◽  
Differential Diagnosis ◽  
Healthy Volunteers ◽  
Lupus Erythematosus ◽  
Clinical Characteristics ◽  
Systemic Lupus ◽  
Control Groups ◽  
Systematic Screening ◽  
Systemic Lupus Erythematosus Diagnosis

Abstract Objective Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis. Methods Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies. Results A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A. Conclusion The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases.

scholarly journals POS0765 LABORATORY RATIOS: A SUBROGATE BIOMARKER FOR DETECTION OF INFECTION IN SLE PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 636.1-636
Author(s):  
Y. Santamaria-Alza ◽  
J. Sanchez-Bautista ◽  
T. Urrego Callejas ◽  
J. Moreno ◽  
F. Jaimes ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Logistic Regression ◽  
Roc Curve ◽  
Lupus Erythematosus ◽  
Statistical Significance ◽  
C Reactive Protein ◽  
Systemic Lupus ◽  
Predictive Capacity ◽  
Cross Sectional ◽  
Reactive Protein

Background:The most common complication in patients with SLE is infection, and its clinical presentation is often indistinguishable from SLE flares. Therefore, laboratory ratios have been evaluated to differentiate between those events. Among them, ESR/CRP1, neutrophil/lymphocyte (NLR)2, and platelet/lymphocyte (PLR)3 ratios have been previously assessed with acceptable performance; however, there is no validation of those ratios in our SLE population.Objectives:To examine the predictive capacity of infection of the lymphocyte/C4 (LC4R), lymphocyte/C3 (LC3R), and ferritin/ESR (FER) ratios in SLE patients, and to evaluate the performance of ESR/CRP, NLR, AND PLR ratios in our SLE population.Methods:We conducted a cross-sectional study of SLE patients admitted to the emergency service at Hospital San Vicente Fundación (HSVF). The HSVF ethics committee approved the execution of the project.Patients were categorized into four groups according to the main cause of hospitalization: (1) infection, (2) flare, (3) infection and flare and, (4) neither infection nor flare.We calculated the median values of the ratios and their respective interquartile ranges for each group. Then, we compared those summary measures using the Kruskal-Wallis test. Subsequently, we assessed the predictive capacity of infection of each ratio using ROC curve. Finally, we carried out a logistic regression model.Results:A total of 246 patients were included, among them 90.7% were women. The median age was 28 years (IQR: 20-35 years). Regarding the outcomes, 37.0% of the patients had flares, 30.9% had neither infection nor flare, 16.7% had an infection and, 15.5% had simultaneously infection and flare. When compared the four groups, statistical significance (p<0.05) was observed. Area under the ROC curve (AUC) for infection prediction was as follows: 0.752 (sensitivity 60.5%, specificity 80.5%) for LC4R, 0.740 (sensitivity 73.2%, specificity 68.3%) for FER, 0.731 (sensitivity 77.6%, specificity 80.5%) for LC3R.In the logistic regression modeling, we observed that an increase in the risk of infection was associated with an LC4R below 66.7 (OR: 6.3, CI: 2.7 – 14.3, p <0.0001), a FER greater than 13.6 (OR: 5.9, CI: 2.8 – 12.1, p <0.0001) and an LC3R below 11.2 (OR: 4.9, CI: 2.4 – 9.8, p <0.0001).The ESR/CRP and PLR performed poorly with an AUC of 0.580 and 0.655, respectively. In contrast, the NLR showed better performance (AUC of 0.709, with a sensitivity of 80.2% and specificity of 55.7%).Figure 1.ROC curves of the evaluated ratiosConclusion:These laboratory ratios could be easy to assay and inexpensive biomarkers to differentiate between infection and activity in SLE patients. The LC4R, FER, and LC3R have a significant diagnostic performance for detecting infection among SLE patients. Of the ratios previously evaluated, ESR/CRP, LPR, NLR, only the latest has an adequate performance in our population.References:[1]Littlejohn E, Marder W, Lewis E, et al. The ratio of erythrocyte sedimentation rate to C-reactive protein is useful in distinguishing infection from flare in systemic lupus erythematosus patients presenting with fever. Lupus. 2018;27(7):1123-1129.[2]Broca-Garcia BE, Saavedra MA, Martínez-Bencomo MA, et al. Utility of neutrophil-to-lymphocyte ratio plus C-reactive protein for infection in systemic lupus erythematosus. Lupus. 2019;28(2):217-222.[3]Soliman WM, Sherif NM, Ghanima IM, EL-Badawy MA. Neutrophil to lymphocyte and platelet to lymphocyte ratios in systemic lupus erythematosus: Relation with disease activity and lupus nephritis. Reumatol Clin. 2020;16(4):255-261s.Disclosure of Interests:None declared

scholarly journals Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus (NPSLE): Can They Be Used as Biomarkers for the Differential Diagnosis of This Disease?

2021 ◽  
Author(s):  
Elias Manca
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Central Nervous System ◽  
Nervous System ◽  
Differential Diagnosis ◽  
Human Body ◽  
Lupus Erythematosus ◽  
Neuropsychiatric Symptoms ◽  
Systemic Lupus ◽  
Neuropsychiatric Systemic Lupus Erythematosus ◽  
The Central Nervous System

AbstractSystemic lupus erythematosus is a complex immunological disease where both environmental factors and genetic predisposition lead to the dysregulation of important immune mechanisms. Eventually, the combination of these factors leads to the production of self-reactive antibodies that can target any organ or tissue of the human body. Autoantibodies can form immune complexes responsible for both the organ damage and the most severe complications. Involvement of the central nervous system defines a subcategory of the disease, generally known with the denomination of neuropsychiatric systemic lupus erythematosus. Neuropsychiatric symptoms can range from relatively mild manifestations, such as headache, to more severe complications, such as psychosis. The evaluation of the presence of the autoantibodies in the serum of these patients is the most helpful diagnostic tool for the assessment of the disease. The scientific progresses achieved in the last decades helped researchers and physicians to discover some of autoepitopes targeted by the autoantibodies, although the majority of them have not been identified yet. Additionally, the central nervous system is full of epitopes that cannot be found elsewhere in the human body, for this reason, autoantibodies that selectively target these epitopes might be used for the differential diagnosis between patients with and without the neuropsychiatric symptoms. In this review, the most relevant data is reported with regard to mechanisms implicated in the production of autoantibodies and the most important autoantibodies found among patients with systemic lupus erythematosus with and without the neuropsychiatric manifestations.

AB0522 Clinical Characteristics of Muscular Symptoms in Patients with Systemic Lupus Erythematosus

2014 ◽  
Vol 73 (Suppl 2) ◽  
pp. 979.1-979
Author(s):  
K. Noda ◽  
M. Yoshiga ◽  
K. Otani ◽  
H. Ito ◽  
K. Hirai ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Characteristics ◽  
Systemic Lupus

TNF-related apoptosis-inducing ligand is involved in neutropenia of systemic lupus erythematosus

Blood ◽  
2004 ◽  
Vol 104 (1) ◽  
pp. 184-191 ◽  
Author(s):  
Wataru Matsuyama ◽  
Masuki Yamamoto ◽  
Ikkou Higashimoto ◽  
Ken-ichi Oonakahara ◽  
Masaki Watanabe ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Healthy Volunteers ◽  
Lupus Erythematosus ◽  
Laboratory Finding ◽  
Significant Negative Correlation ◽  
Trail Receptor ◽  
Death Domain ◽  
Systemic Lupus ◽  
Inhibitory Protein

Abstract Neutropenia is a common laboratory finding in systemic lupus erythematosus (SLE). However, the molecular mechanism of SLE neutropenia has not been fully explained. In this study, we examined whether TNF-related apoptosis-inducing ligand (TRAIL) is involved in the pathogenesis of SLE neutropenia using samples from SLE patients. Serum TRAIL levels in SLE patients with neutropenia were significantly higher than those of SLE patients without neutropenia and healthy volunteers. Serum TRAIL levels showed a significant negative correlation with neutrophil counts in SLE patients. The expression of TRAIL receptor 3 was significantly lower in SLE patients with neutropenia than in patients without neutropenia or in healthy volunteers. Treatment with glucocorticoids negated the decrease of TRAIL receptor 3 expression on neutrophils of SLE patients. TRAIL may accelerate neutrophil apoptosis of neutrophils from SLE patients, and autologous T cells of SLE patients, which express TRAIL on surface, may kill autologous neutrophils. Interferon gamma and glucocorticoid modulated the expression of TRAIL on T cells of SLE patients and also modulated the expression of cellular Fas-associating protein with death domain–like interleukin-1β–converting enzyme (FLICE)–inhibitory protein (cFLIP), an inhibitor of death receptor signaling, in neutrophils. Thus, our results provide a novel insight into the molecular pathogenesis of SLE neutropenia.

scholarly journals AB0302 FACTORS ASSOCIATED WITH GESTATIONAL DIABETES MELLITUS (GDM) IN A MULTI-ETHNIC SYSTEMIC LUPUS ERYTHEMATOSUS (SLE) COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1177.1-1177
Author(s):  
S. S. Shaharir ◽  
R. Mustafar ◽  
M. S. Mohamed Said ◽  
R. Abd Rahman
Keyword(s):  
Diabetes Mellitus ◽  
Systemic Lupus Erythematosus ◽  
Logistic Regression ◽  
Gestational Diabetes ◽  
Gestational Diabetes Mellitus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Factors Associated ◽  
In Pregnancy

Background:The risks of insulin resistance and diabetes mellitus are elevated in systemic lupus erythematosus (SLE) patients. The use of glucocorticoid and anti-double stranded DNA antibodies positive are among the factors reported to be associated with the risk of gestational diabetes mellitus (GDM) in SLE patients. However, the relationship between GDM in Asian SLE patients is still obscure.Objectives:To determine the prevalence of gestational diabetes mellitus (GDM) in a multi-ethnic SLE cohort in Malaysia and the associated risk factors.Methods:This was a retrospective study of SLE pregnant women who have completed their antenatal care in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) from 2004 until 2019. Screening and diagnosis of gestational diabetes mellitus (GDM) were as recommended in the guidelines by the Ministry of Health Malaysia. Information on SLE disease activity and treatment at 6 months before pregnancy and during pregnancy were determined from the medical records. Univariate and multi-variable logistic regression analyses were performed to determine the factors associated with GDM in the SLE patients.Results:A total of 89 patients with 202 pregnancies were included in the study. Malay was the predominant ethnic in this cohort (n=82, 67.2%), followed by Chinese (n=33,27.0%) and Indian (n=7, 5.7%). The most common system involvement of SLE was musculoskeletal (n=91, 74.6%), followed by haematological (n=78, 63.9%), lupus nephritis (54.9%, n=67) and mucocutaneous (n=66, 54.1%). The prevalence of GDM was 8.9% (n=18). More patients with GDM had positive anti-cardiolipin IgG antibody (aCL IgG) and lupus anticoagulant (LA) antibody as compared to the patients with no GDM, (55.6% vs 25.8%, p=0.01) and (50.0% vs 25.4%, p=0.05) respectively. On the other hand, the use of hydroxychloroquine (HCQ) in pregnancy was significantly lower in GDM patients (11.1%) as compared to no GDM group (39.1%), p=0.02. There was no significant difference in the ethnicity, SLE system involvement, disease activity status and immunosupressant use including steroid, azathioprine and cyclosporine A at 6 months before and during pregnancy between the GDM and non-GDM group. A forward logistic regression which include aCL IgG, LA and HCQ use in pregnancy, only the HCQ use remained significantly associated with lower risk of GDM in the model with OR= 0.12, 95% C.I = 0.02-0.94, p=0.04.Conclusion:Our study demonstrates the potential benefit of hydroxychloroquine in reducing the risk of gestational diabetes mellitus in SLE patients. The prevalence of antiphospholipid antibodies particularly aCL IgG and LA was found to be higher among patients with GDM. Further prospective studies are needed to confirm this association.References:[1]Dong Y, Dai Z, Wang Z, et al. Risk of gestational diabetes mellitus in systemic lupus erythematosus pregnancy: a systematic review and meta-analysis. BMC Pregnancy and Childbirth. 2019 May;19(1):179. DOI: 10.1186/s12884-019-2329-0.Disclosure of Interests:None declared

Prognostic nutritional index is correlated with disease activity in patients with systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1697-1705 ◽  
Author(s):  
S S Ahn ◽  
S M Jung ◽  
J J Song ◽  
Y-B Park ◽  
S-W Lee
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Lymphocyte Count ◽  
Prognostic Nutritional Index ◽  
Systemic Lupus ◽  
Nutritional Index ◽  
Laboratory Variables

The prognostic nutritional index (PNI), which is calculated using serum albumin level and total lymphocyte count in the peripheral blood, is regarded as an index that reflects the immunonutritional status of patients. PNI was calculated in 217 systemic lupus erythematosus (SLE) patients according to the following formula: 10 × serum albumin value (g/dL) + 0.005 × peripheral lymphocyte count (/mm3). Pearson’s correlation analysis was used to elucidate the correlation between continuous variables. Linear and logistic regression analyses were performed to assess the correlation between laboratory variables and SLE Disease Activity Index-2000 (SLEDAI-2 K) and to differentiate between active and inactive SLE. Ninety-three patients were classified as active SLE (SLEDAI-2 K ≥ 5) and 124 as inactive SLE. Patients with active SLE exhibited lower median PNI than those with inactive SLE (39.0 vs. 49.1, p < 0.001). Multivariable logistic regression analysis revealed PNI as an independent predictor of active SLE. Multivariable linear regression analysis revealed that PNI was significantly correlated with laboratory variables of SLEDAI-2 K, erythrocyte sedimentation rate, C-reactive protein and SLEDAI-2 K. Furthermore, in patients who switched from active to inactive SLE after treatment ( n = 55), PNI increased as disease activity improved ( p < 0.001), which suggests that PNI may be useful for estimating SLE activity.

scholarly journals PSEUDOTUMOR CEREBRI AS A DIFFERENTIAL DIAGNOSIS FOR VISION LOSS IN SYSTEMIC LUPUS ERYTHEMATOSUS: CASE REPORT

2019 ◽  
Author(s):  
MARCO FELIPE MACÊDO ALVES ◽  
CAIO FELIPE FARIAS BARROS ◽  
JARDELINA BRENA ROCHA LEITE ◽  
MARINA ACEVEDO ZARZAR DE MELO ◽  
PEDRO JOSÉ GALVÃO FREIRE ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Differential Diagnosis ◽  
Case Report ◽  
Lupus Erythematosus ◽  
Vision Loss ◽  
Pseudotumor Cerebri ◽  
Systemic Lupus ◽  
Systemic Lupus Erythematosus Case
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