Naja naja atraVenom Protects against Manifestations of Systemic Lupus Erythematosus in MRL/lpr Mice

Systemic lupus erythematosus (SLE) is an autoimmune disease and effective therapy for this pathology is currently unavailable. We previously reported that oral administration ofNaja naja atravenom (NNAV) had anti-inflammatory and immune regulatory actions. We speculated that NNAV may have therapeutic effects in MRL/lpr SLE mice. Twelve-week-old MRL/lpr mice received oral administration of NNAV (20, 40, and 80 μg/kg) orTripterygium wilfordii polyglycosidium(10 mg/kg) daily for 16 weeks. The effects of NNAV on SLE manifestations, including skin erythema, proteinuria, and anxiety-like behaviors, were assessed with visual inspection and Multistix 8 SG strips and open field test, respectively. The pathology of spleen and kidney was examined with H&E staining. The changes in autoimmune antibodies and cytokines were determined with ELISA kits. The results showed that NNAV protected against the manifestation of SLE, including skin erythema and proteinuria. In addition, although no apparent histological change was found in liver and heart in MRL/lpr SLE mice, NNAV reduced the levels of glutamate pyruvate transaminase and creatine kinase. Furthermore, NNAV increased serum C3 and reduced concentrations of circulating globulin, anti-dsDNA antibody, and inflammatory cytokines IL-6 and TNF-α. NNAV also reduced lymphadenopathy and renal injury. These results suggest that NNAV may have therapeutic values in the treatment of SLE by inhibiting autoimmune responses.

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When systemic lupus erythematosus affects vision: a rare presentation of this condition

BMJ Case Reports ◽

10.1136/bcr-2019-229382 ◽

2020 ◽

Vol 13 (1) ◽

pp. e229382

Author(s):

Tiago Gama Ramires ◽

Luísa Vieira ◽

Nuno Riso ◽

Maria Francisca Moraes-Fontes

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Blurred Vision ◽

Rare Presentation ◽

Complement Components ◽

Oral Ulcers ◽

Dsdna Antibody ◽

Rare Manifestation ◽

Retinal Vascular Tortuosity

A 23-year-old woman with fever, oral ulcers, arthalgias and weight loss of 2-week duration suddenly developed blurred vision, with reduced visual acuity, cotton wool exudates and retinal vascular tortuosity. Laboratory testing revealed anaemia, lymphopaenia, positive antinuclear antibody and high anti-dsDNA antibody titre with low complement components. There was no evidence of infection, clinching the diagnosis of lupus retinopathy. Steroid therapy alone was highly effective and was also accompanied by a normalisation of haemoglobin and lymphocyte counts, after which azathioprine was added. Hydroxychloroquine was introduced after resolution of retinal changes. Immunosuppressive therapy was progressively tapered over the course of 12 months and then discontinued, and the patient remains in remission 48 months after the initial presentation. Our patient exemplifies a very rare manifestation of systemic lupus erythematosus. We emphasise the importance of its early detection and complexity of treatment in order to reduce visual morbidity.

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The expansion of activated naive DNA autoreactive B cells and its association with disease activity in systemic lupus erythematosus patients

Arthritis Research & Therapy ◽

10.1186/s13075-021-02557-0 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Kittikorn Wangriatisak ◽

Chokchai Thanadetsuntorn ◽

Thamonwan Krittayapoositpot ◽

Chaniya Leepiyasakulchai ◽

Thanitta Suangtamai ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

B Cells ◽

Disease Activity ◽

B Cell ◽

Lupus Erythematosus ◽

Systemic Lupus ◽

Autoreactive B Cells ◽

Dsdna Antibody ◽

Cell Subpopulations ◽

B Cell Subsets

Abstract Background Autoreactive B cells are well recognized as key participants in the pathogenesis of systemic lupus erythematosus (SLE). However, elucidating the particular subset of B cells in producing anti-dsDNA antibodies is limited due to their B cell heterogeneity. This study aimed to identify peripheral B cell subpopulations that display autoreactivity to DNA and contribute to lupus pathogenesis. Methods Flow cytometry was used to detect total B cell subsets (n = 20) and DNA autoreactive B cells (n = 15) in SLE patients’ peripheral blood. Clinical disease activities were assessed in SLE patients using modified SLEDAI-2 K and used for correlation analyses with expanded B cell subsets and DNA autoreactive B cells. Results The increases of circulating double negative 2 (DN2) and activated naïve (aNAV) B cells were significantly observed in SLE patients. Expanded B cell subsets and DNA autoreactive B cells represented a high proportion of aNAV B cells with overexpression of CD69 and CD86. The frequencies of aNAV B cells in total B cell populations were significantly correlated with modified SLEDAI-2 K scores. Further analysis showed that expansion of aNAV DNA autoreactive B cells was more related to disease activity and serum anti-dsDNA antibody levels than to total aNAV B cells. Conclusion Our study demonstrated an expansion of aNAV B cells in SLE patients. The association between the frequency of aNAV B cells and disease activity patients suggested that these expanded B cells may play a role in SLE pathogenesis.

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AB0013 ASSOCIATION BETWEEN STAT4 POLYMORPHISM AND MANIFESTATIONS OF SLE

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.3470 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 1041.1-1041

Author(s):

V. Agarwal ◽

S. Kakati ◽

P. Debbaruah

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Indian Population ◽

Association Studies ◽

Statistical Significance ◽

Elevated Serum ◽

Systemic Lupus ◽

Cutaneous Manifestations ◽

Genotype Group ◽

Dsdna Antibody

Background:SNP rs7574865, located within the third intron of STAT4 gene at chromosome 2, has been associated with susceptibility to SLE among different ethnic groups.1,2 Interestingly, we recently have documented an association between this gene and susceptibility to systemic lupus erythematosus (SLE) in Indian population.3Objectives:To determine whether the STAT4 (rs7574865) SNP is associated with clinical and immunological manifestations in SLE.Methods:The study was carried out on 100 unrelated SLE (SLICC criteria 2012) patients from North-East India. Genotyping of STAT4 rs7574865 SNP was done using Taqman probe and Real-Time Polymerase chain reaction. An association study was performed between the alleles and genotypes of STAT4 rs7574865 with the clinical and immunological manifestations included in the SLE SLICC classification criteria. For all analysis, the statistical significance was fixed at 5% level of significance (p < 0.05).Results:The mean duration of illness was 2.69±2.55 years. Cases and Controls remained in Hardy-Weinberg equilibrium.The occurrence of Photosensitivity and hyperpigmentation was significantly higher in TT genotype group (97.22% and 77.77%, respectively) with p <0.001 in each case.SLE patients with nephritis (Albuminuria >500mg/24 hours) and elevated serum creatinine were both significantly higher in TT genotype group as compared to GT and GG (p< 0.001 and p=0.001 respectively).The Anti-dsDNA antibody was significantly associated with TT genotype (p <0.001).Conclusion:Our study provides evidence regarding the association between STAT4 rs7574865 gene polymorphism is risk factor for cutaneous manifestations, Lupus nephritis and Anti ds-DNA positivity in SLE. So, our findings reinforce the need for further association studies including prospective studies with larger subjects in order to replicate such findings.References:[1]Graham RR, Ph D, Hom G, Ph D, Behrens TW, Bakker PIW De, et al. and the Risk of Rheumatoid Arthritis and Systemic Lupus Erythematosus. N Engl J Med. 2007;357(10):977–86.[2]Yuan H, Feng JB, Pan HF, Qiu LX, Li LH, Zhang N, et al. A meta-analysis of the association of STAT4 polymorphism with systemic lupus erythematosus. Mod Rheumatol. 2010;20(3):257–62.[3]Gupta V, Kumar S, Pratap A, Singh R, Kumari R, Kumar S, et al. Association of ITGAM, TNFSF4, TNFAIP3 and STAT4 gene polymorphisms with risk of systemic lupus erythematosus in a North Indian population. Lupus. 2018;27(12):1973–9.Disclosure of Interests:None declared

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Dysregulated T Cell Activation and Aberrant Cytokine Expression Profile in Systemic Lupus Erythematosus

Mediators of Inflammation ◽

10.1155/2019/8450947 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 4

Author(s):

Haiyan Zhou ◽

Bojiang Li ◽

Jing Li ◽

Tongqian Wu ◽

Xiaoqian Jin ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

T Cell ◽

Lupus Erythematosus ◽

Critical Role ◽

Cytokine Expression ◽

Healthy Controls ◽

Systemic Lupus ◽

Hla Dr ◽

Dsdna Antibody

Accumulating evidence indicates a critical role for T cells and relevant cytokines in the pathogenesis of systemic lupus erythematosus (SLE). However, the specific contribution of T cells together with the related circulating cytokines in disease pathogenesis and organ involvement is still not clear. In the current study, we investigated relevant molecule expressions and cytokine levels in blood samples from 49 SLE patients and 22 healthy control subjects. The expression of HLA-DR and costimulatory molecules on T cells was evaluated by flow cytometry. Concentrations of serum C-reactive protein, erythrocyte sedimentation rate, anti-double-stranded DNA (anti-dsDNA) antibody, total lgG, complement 3, and complement 4 were measured. Serum cytokines and chemokines were measured by a cytometric bead array assay. Elevated frequencies of HLA-DR+ T cells and ICOS+ T cells were observed in SLE patients with positive anti-dsDNA antibodies compared with those in healthy controls (P<0.001). The expression of HLA-DR+ T cells was positively correlated with SLEDAI (r=0.15, P<0.01). Furthermore, levels of serum IL-6, MCP-1, TNFRI, IL-10, IL-12, and CCL20 were higher in SLE patients compared with healthy controls. In addition, patients with hematologic manifestations displayed elevated frequencies of HLA-DR+ T cells and ICOS+ T cells. Patients with renal manifestations had a decreased frequency of TIGIT+ T cells. These results suggested a dysregulated T cell activity and cytokine expression profiles in SLE subjects. We also developed a chemokine and cytokine profiling strategy to predict the activity of SLE, which has clinical implication for better monitoring the flares and remission during the course of SLE and for assessing therapeutic interventions.

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Polymorphisms of MFGE8 are associated with susceptibility and clinical manifestations through gene expression modulation in Koreans with systemic lupus erythematosus

Scientific Reports ◽

10.1038/s41598-019-55061-6 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Wook-Young Baek ◽

Ji-Min Woo ◽

Hyoun-Ah Kim ◽

Ju-Yang Jung ◽

Chang-Hee Suh

Keyword(s):

Gene Expression ◽

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Milk Fat ◽

Clinical Manifestations ◽

Αvβ3 Integrin ◽

Apoptotic Cells ◽

Systemic Lupus ◽

Dsdna Antibody

AbstractSystemic lupus erythematosus (SLE) is characterized by impaired clearance of apoptotic cells. Milk fat globule epidermal growth factor 8 (MFGE8) is a protein that connects αvβ3 integrin on phagocytic macrophages with phosphatidylserine on apoptotic cells. We investigated whether genetic variation of the MFGE8 gene and serum MFGE8 concentration are associated with SLE. Single nucleotide polymorphisms (SNPs) were genotyped and serum concentrations were analyzed. The rs2271715 C allele and rs3743388 G allele showed higher frequency in SLE than in healthy subjects (HSs). Three haplotypes were found among 4 SNPs (rs4945, rs1878327, rs2271715, and rs3743388): AACG, CGCG, and CGTC. CGCG haplotype was significantly more common in SLE than in HSs. rs4945 was associated with the erythrocyte sedimentation rate and rs1878327 was associated with alopecia, C-reactive protein, complement 3, anti-dsDNA antibody, and high disease activity. rs2271715 and rs3743388 were associated with renal disease, cumulative glucocorticoid dose, and cyclophosphamide and mycophenolate mofetil use. Serum MFGE8 concentrations were significantly higher in SLE than in HSs. Furthermore, the levels of MFGE8 were significantly higher in SLE than HSs of the rs2271715 CC genotype. In conclusion, MFGE8 genetic polymorphisms are associated not only with susceptibility to SLE but also with disease activity through modulation of gene expression.

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Clinical evaluation of total and high-avidity anti-dsDNA antibody assays for the diagnosis of systemic lupus erythematosus

Lupus ◽

10.1177/0961203319877243 ◽

2019 ◽

Vol 28 (12) ◽

pp. 1387-1396 ◽

Cited By ~ 1

Author(s):

W Yuan ◽

H Cao ◽

P Wan ◽

R Shi ◽

S Zhou ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Clinical Manifestations ◽

Superior Performance ◽

High Avidity ◽

Systemic Lupus ◽

Dsdna Antibody ◽

In Vitro Diagnostic

Background This study evaluated the diagnostic performances of total and high-avidity (HA) anti-dsDNA enzyme immunoassays (EIA) in Chinese systemic lupus erythematosus (SLE) patients. Methods A total of 410 serum samples from 217 SLE patients, 54 patients with other systemic autoimmune diseases, and 139 healthy subjects were tested on total and HA anti-dsDNA EIA, as well as three commercial in vitro diagnostic kits: BioPlex 2200 ANA Screen, Kallestad anti-dsDNA EIA, and Crithidia Lucilae IFA. The disease activities of SLE patients were assessed using the modified SLE Disease Activity Index. The diagnostic performances of each assay were analyzed using Analyse-it software. Results The diagnostic performances of the total and HA anti-dsDNA EIA kits were comparable to other commercially available in vitro diagnostic assays. Receiver operating characteristic curve analysis demonstrated an area under the curve ranging from 0.85 to 0.89, with the total anti-dsDNA kit demonstrating the highest sensitivity and the HA kit showing higher specificity. An overall agreement of >90% was observed between the total and HA anti-dsDNA EIA kits and commercially available quantitative anti-dsDNA kits. The ratio of HA to total anti-dsDNA antibody was significantly higher among SLE patients with active disease status and/or kidney damage. All assays exhibited a significant correlation with disease activity and multiple clinical manifestations. Conclusions While the clinical performances of various anti-dsDNA assays showed adequate agreements, the BioPlex 2200 anti-dsDNA assay demonstrated the highest positive likelihood ratio and odds ratio. The HA anti-dsDNA EIA kit in association with the total anti-dsDNA kit provided superior performance in SLE diagnosis and monitoring disease activity.

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Galectin-9 is an easy to measure biomarker for the interferon signature in systemic lupus erythematosus and antiphospholipid syndrome

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2018-213497 ◽

2018 ◽

Vol 77 (12) ◽

pp. 1810-1814 ◽

Cited By ~ 20

Author(s):

Lucas L van den Hoogen ◽

Joël A G van Roon ◽

Jorre S Mertens ◽

Judith Wienke ◽

Ana Pinheiro Lopes ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Area Under The Curve ◽

Serum Levels ◽

Complement C3 ◽

Tumour Necrosis Factor Receptor ◽

Systemic Lupus ◽

Dsdna Antibody

ObjectiveThe interferon (IFN) signature is related to disease activity and vascular disease in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) and represents a promising therapeutic target. Quantification of the IFN signature is currently performed by gene expression analysis, limiting its current applicability in clinical practice. Therefore, the objective of this study was to establish an easy to measure biomarker for the IFN signature.MethodsSerum levels of galectin-9, CXCL-10 (IP-10) and tumour necrosis factor receptor type II (TNF-RII) were measured in patients with SLE, SLE+APS and primary APS (PAPS) and healthy controls (n=148) after an initial screening of serum analytes in a smaller cohort (n=43). Analytes were correlated to measures of disease activity and the IFN signature. The performance of galectin-9, CXCL-10 and TNF-RII as biomarkers to detect the IFN signature was assessed by receiver operating characteristic curves.ResultsGalectin-9, CXCL-10 and TNF-RII were elevated in patients with SLE, SLE+APS and PAPS (p<0.05) and correlated with disease activity and tissue factor expression. Galectin-9 correlated stronger than CXCL-10 or TNF-RII with the IFN score (r=0.70, p<0.001) and was superior to CXCL-10 or TNF-RII in detecting the IFN signature (area under the curve (AUC) 0.86). Importantly, in patients with SLE(±APS), galectin-9 was also superior to anti-dsDNA antibody (AUC 0.70), or complement C3 (AUC 0.70) and C4 (AUC 0.78) levels in detecting the IFN signature.ConclusionGalectin-9 is a novel, easy to measure hence clinically applicable biomarker to detect the IFN signature in patients with systemic autoimmune diseases such as SLE and APS.

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