Genetic polymorphisms of dsRNA ligating pattern recognition receptors TLR3, MDA5, and RIG-I. Association with systemic lupus erythematosus and clinical phenotypes

Systemic lupus erythematosus (SLE) is an autoimmune disease with unknown etiology affecting more than one million individuals each year. It is characterized by B- and T-cell hyperactivity and by defects in the clearance of apoptotic cells and immune complexes. Understanding the complex process involved and the interaction between various cytokines, chemokines, signaling molecules, and pattern-recognition receptors (PRRs) in the immune pathways will provide valuable information on the development of novel therapeutic targets for treating SLE. In this paper, we review the immunopathological roles of novel cytokines, chemokines, signaling molecules, PRRs, and their interactions in immunoregulatory networks and suggest how their disturbances may implicate pathological conditions in SLE.

Download Full-text

SAT0240 THE PROGNOSIS OF TWO DISTINCT CLINICAL PHENOTYPES OF SLE-PAH

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4520 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1063.2-1063

Author(s):

J. Wang ◽

Y. Feng ◽

Y. Lei ◽

X. Zhang

Keyword(s):

Systemic Lupus Erythematosus ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Lupus Erythematosus ◽

Right Heart Catheterization ◽

Heart Catheterization ◽

Systemic Lupus ◽

Clinical Phenotypes ◽

Weighted Score ◽

Pulmonary Arterial

Background:Based on the characteristics of systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH), Sunet alhas put forward a scoring system to distinguish two clinical phenotypes as vasculitic and vasculopathic subtypes[1]. A weighted score ≥2 suggested a vasculitic subtype by combining two factors: The time interval between SLE and PAH diagnosis <2 years and ≥2 years were 1 and 0 point; SLE Disease Activity Index (SLEDAI) >9, 5-9 and <5 were 2, 1, 0 point, respectively. While the vasculitic subtype seemed to have poorer prognosis in Sun’s research, other study has shown controversial result[2].Objectives:To find out the prognosis of two distinct clinical phenotypes of SLE-PAH.Methods:Between 2008 and 2019, a SLE-PAH cohort confirmed by right heart catheterization (RHC) from Guangdong Provincial People’s Hospital was included. Other groups of pulmonary hypertension were excluded. Based on the scoring system, patients were divided into vasculitic (weighted score≥2) and vasculopathic subtypes (weighted score<2). The endpoint was PAH-related mortality. Survival status were confirmed by clinic follow-up data or phone call.Results:A total of 53 SLE-PAH patients were enrolled. The cases of vasculitic and vasculopathic subtype were 14 and 39, respectively. Ten endpoint events occurred. Eight attributed to PAH and the cause could not be traced in two which were still included in study. The pooled 1-, 3-, 5-year survival rates were 85.7%, 78.6%, 65.5% in vasculitic subtype, and 93.9%, 87.5%, 87.5% in vasculopathic subtype, respectively. Kaplan-Meier analysis showed vasculitic subtype tended to have a poorer prognosis than vasculopathic subtype (p=0.16, HR 2.4, 95%CI 0.5-13.8, figure 1).Figure 1.Survival curves for patients with systemic lupus erythematosus-pulmonary arterial hypertension (SLE-PAH) in two distinct subtypes. RHC, Right Heart Catheterization.Conclusion:The prognosis of the two phenotypes of SLE-PAH was statistically indifferent while the vasculitic subtype showed a trend of worse prognosis. Further studies are needed.References:[1]F. Sun, Y. Lei, W. Wu, L. Guo, K. Wang, Z. Chen, W. Xu, X. Wang, T. Li, X. Zhang, S. Ye, Two distinct clinical phenotypes of pulmonary arterial hypertension secondary to systemic lupus erythematosus, Ann Rheum Dis 78(1) (2019) 148-150.[2]J. Qian, M. Li, J. Zhao, Q. Wang, Z. Tian, X. Zeng, Inflammation in SLE-PAH: good news or not?, Ann Rheum Dis (2018).0:1–2. doi:10.1136/annrheumdis-2018-214605Disclosure of Interests:None declared

Download Full-text

Genetic Polymorphisms in Patients With Systemic Lupus Erythematosus and Jaccoud Arthropathy

JCR Journal of Clinical Rheumatology ◽

10.1097/rhu.0000000000001653 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Anna Paula Mota Duque Sousa ◽

Giselle Calasans de Souza Costa ◽

Gustavo Nunes de Oliveira Costa ◽

Lúcio Macedo Barbosa ◽

Maria Fernanda Rios Grassi ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Genetic Polymorphisms ◽

Lupus Erythematosus ◽

Systemic Lupus

Download Full-text

CLINICAL PHENOTYPES OF SYSTEMIC LUPUS ERYTHEMATOSUS WITH REGARD TO AGE AT DISEASE ONSET

Traditional medicine and pharmacology. Achievements, innovations, and alternatives ◽

10.46299/isg.2021.mono.med.ii-56-61 ◽

2021 ◽

pp. 56-61

Author(s):

Oleg Iaremenko ◽

◽

Daria Koliadenko

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Disease Onset ◽

Systemic Lupus ◽

Clinical Phenotypes

Download Full-text

The Lectin Pathway of Complement Activation in Patients with Systemic Lupus Erythematosus

The Journal of Rheumatology ◽

10.3899/jrheum.171033 ◽

2018 ◽

Vol 45 (8) ◽

pp. 1136-1144 ◽

Cited By ~ 13

Author(s):

Anne Troldborg ◽

Steffen Thiel ◽

Marten Trendelenburg ◽

Justa Friebus-Kardash ◽

Josephine Nehring ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Pattern Recognition ◽

Disease Activity ◽

Lupus Erythematosus ◽

Complement Activation ◽

Lectin Pathway ◽

Classical Pathway ◽

Systemic Lupus ◽

Over Time ◽

Repeated Samples

Objective.The pathogenesis of systemic lupus erythematosus (SLE) involves complement activation. Activation of complement through the classical pathway (CP) is well established. However, complement activation through pattern recognition not only happens through the CP, but also through the lectin pathway (LP). We investigated the hypothesis that the LP is activated in SLE and involved in the pathogenesis of the disease.Methods.Using immunoassays developed in-house, we measured concentrations of LP proteins in a cohort of 372 patients with SLE and 170 controls. We estimated complement activation measuring total C3, and investigated whether LP protein concentrations were associated with complement activation and disease activity. Protein changes and disease activity over time were assessed in a cohort of 52 patients with SLE followed with repeated samples over a 5-year period.Results.Concentrations of LP proteins in SLE were altered compared with controls. The differences observed in LP proteins associated with complement activation were reflected by a decrease in total C3. The pattern recognition molecules (M-ficolin, CL-L1, and CL-K1), the serine protease (MASP-3), and the associated protein (MAp19) displayed a negative correlation with disease activity. Changes in MASP-2 concentrations over time correlated significantly with increased disease activity. Association between active proteinuria and serum concentration was observed for MASP-3 and MAp19.Conclusion.In patients with SLE, we measured specific changes in LP proteins that are associated with complement activation and disease activity, indicating that the LP is activated in patients with SLE. These novel findings substantiate the involvement of the LP in SLE.

Download Full-text

Association study of glucocorticoid receptor genetic polymorphisms with efficacy of glucocorticoids in systemic lupus erythematosus: A prospective cohort study

Autoimmunity ◽

10.3109/08916934.2013.830714 ◽

2013 ◽

Vol 46 (8) ◽

pp. 531-536 ◽

Cited By ~ 24

Author(s):

Yan-Feng Zou ◽

Jian-Hua Xu ◽

Fen Wang ◽

Shuang Liu ◽

Jin-Hui Tao ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Cohort Study ◽

Glucocorticoid Receptor ◽

Association Study ◽

Genetic Polymorphisms ◽

Prospective Cohort Study ◽

Lupus Erythematosus ◽

Prospective Cohort ◽

Systemic Lupus

Download Full-text

Effect of genetic polymorphisms on effectiveness of low-dose azathioprine in Japanese patients with systemic lupus erythematosus

American Journal of Health-System Pharmacy ◽

10.2146/ajhp120179 ◽

2012 ◽

Vol 69 (23) ◽

pp. 2072-2078 ◽

Cited By ~ 4

Author(s):

Ayumu Nagamine ◽

Miki Takenaka ◽

Tohru Aomori ◽

Yuko Okada ◽

Keiju Hiromura ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Genetic Polymorphisms ◽

Lupus Erythematosus ◽

Low Dose ◽

Japanese Patients ◽

Systemic Lupus

Download Full-text

Prospective Study of Clinical Phenotypes in Neuropsychiatric Systemic Lupus Erythematosus; Multidisciplinary Approach to Diagnosis and Therapy

The Journal of Rheumatology ◽

10.3899/jrheum.120545 ◽

2012 ◽

Vol 39 (11) ◽

pp. 2118-2126 ◽

Cited By ~ 36

Author(s):

ELISABETH J.M. ZIRKZEE ◽

GERDA M. STEUP-BEEKMAN ◽

ROOS C. van der MAST ◽

EDUARD L.E.M. BOLLEN ◽

NIC J.A. van der WEE ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Symptomatic Treatment ◽

Anticardiolipin Antibodies ◽

Experimental Science ◽

Pathogenetic Mechanism ◽

Systemic Lupus ◽

Clinical Phenotypes ◽

Neuropsychiatric Systemic Lupus Erythematosus ◽

Therapeutic Decisions

Objective.To describe clinical phenotypes in neuropsychiatric systemic lupus erythematosus (NPSLE).Methods.Data were prospectively collected in the Leiden NPSLE referral clinic, where patients suspected of having NPSLE are assessed in a standardized multidisciplinary manner. In consensus meetings, all medical specialists agreed on therapeutic strategy based on the suspected pathogenetic mechanism of NPSLE in the individual patient. An algorithm illustrates the process of decision-making during the consensus meeting. Clinical phenotypes are described, classified by pathogenetic mechanism.Results.One hundred consecutive patients were evaluated, of whom 71 had SLE (29 patients did not fulfill ≥ 4 American College of Rheumatology criteria) and 46 had NPSLE. Primary NPSLE was diagnosed in 38 patients (53%) and could be differentiated in 21 patients (55%) with inflammatory NPSLE who were advised on immunosuppressive therapy, 12 patients (32%) with ischemic NPSLE who were advised on anticoagulant therapy, and 5 patients (13%) with undefined NPSLE who were advised symptomatic treatment only. Cognitive dysfunction and higher level of disease activity were associated with inflammatory NPSLE. Although presence of immunoglobulin G anticardiolipin antibodies and abnormalities on magnetic resonance imaging (MRI) were associated with ischemic NPSLE, abnormalities on MRI lacked specificity to distinguish phenotypes. A history of renal disease and use of corticosteroids were associated with secondary NPSLE.Conclusion.We describe multidisciplinary consensus as a standard for diagnosing and defining phenotypes in NPSLE. These phenotypes show specific characteristics, which can be used to support diagnosis and guide therapeutic decisions. Clinical phenotyping and selection of patients becomes increasingly important when advances in experimental science lead to new targets for therapy in NPSLE.

Download Full-text

Correlation Between Mex-Sledai and Mean Platelet Volume In Systemic Lupus Erythematosus Patients

Indonesian Journal of Rheumatology ◽

10.37275/ijr.v12i2.158 ◽

2021 ◽

Vol 12 (2) ◽

pp. 293-301

Author(s):

Dr. Ayu Paramaiswari,SpPD, K-R ◽

Dody Hendro Susilo ◽

Deddy Nur Wachid Achadiono

Keyword(s):

Systemic Lupus Erythematosus ◽

Negative Correlation ◽

Lupus Erythematosus ◽

Mean Platelet Volume ◽

Previous History ◽

Platelet Activity ◽

Systemic Lupus ◽

Platelet Volume ◽

Early Detection Of Disease ◽

Clinical Phenotypes

A B S T R A C TBackground. Systemic lupus erythematosus (SLE) is a chronic autoimmunedisease which has a variety of clinical phenotypes with a complex clinical course.The clinical phenotypes are highly variable which can be characterized by acuteattacks, active periods, controllable or remission. Mean platelet volume (MPV) is astraightforward accessible indicator of platelet activity and is associated withsystemic inflammation. The routine usage of MPV as markers for disease activityin SLE remains problematic. Early detection of disease progression is pivotal in themanagement of SLE for obtaining better outcomes. Objective. The study aimed toconfirm that the measurement of the disease severity in patients with SLE usingMex-SLEDAI has a negative correlation with the decrease of MPV value. Methods.This cross-sectional analytic descriptive study was conducted using secondary datafrom the medical records of patients with SLE older than 18 years of age who werenot taking antiplatelets in the Internal Medicine policlinic of Dr. Sardjito GeneralHospital in 2018. Patients with a previous history of cardiovascular andcerebrovascular events, malignancies, receiving a treatment for infections,including sepsis, chronic infections (i.e. tuberculosis, cytomegalovirus, herpessimplex, herpes zoster), HIV, hepatitis B or hepatitis C, and incomplete data ofmedical record were excluded. The correlation between SLEDAI Mex and MPVvalues was evaluated using the Spearman's correlation test. Results. Sixty-sevensubjects (65 women, 2 men) aged 34 ± 11 years were recruited in the study. Themedian duration of diagnosis was 38,2 ± 45,7 months. Arthritis, skin rash andphotosensitivity were identified in 81,1%, 53,7%, and 46,3% of patients,respectively. The Mex-SLEDAI score ranged from 0 to 16. The average of MPV valueis 9.73 ± 1.21 fL. A significant correlation between MPV and SLEDAI Mex wasobserved (p = 0.03 (p <0.05), r = -0.255). Conclusion. The more severe SLE diseaseactivity (based on the Mex-SLEDAI scoring), the more negative correlation with theMPV value.

Download Full-text