scholarly journals AB0013 ASSOCIATION BETWEEN STAT4 POLYMORPHISM AND MANIFESTATIONS OF SLE

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

scholarly journals Association of Elevated Serum Soluble Cd226 Levels With the Disease Activity and Flares of Systemic Lupus Erythematosus

2021 ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Laboratory Data ◽  
Elevated Serum ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cumulative Probability ◽  
Systemic Lupus ◽  
Dsdna Antibody

Abstract Background: CD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. A soluble form of CD226 (sCD226) is known to be shed from the membrane type of CD226 (mCD226). Although CD226 polymorphism and mCD226 are known to be involved in systemic lupus erythematosus (SLE), the involvement of sCD226 in SLE is still unknown. Therefore, we aimed to reveal the association of sCD226 with SLE.Methods: We measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, and laboratory data. We defined the maximum values of sCD226 in HCs as a cut-off level and compared the cumulative probability of flare for patients with high and low sCD226 levels. Results: Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. Conclusion: Serum sCD226 levels were associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.

scholarly journals Association of elevated serum soluble CD226 levels with the disease activity and flares of systemic lupus erythematosus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miki Nakano ◽  
Masahiro Ayano ◽  
Kazuo Kushimoto ◽  
Shotaro Kawano ◽  
Kazuhiko Higashioka ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Laboratory Data ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cumulative Probability ◽  
Systemic Lupus ◽  
Dsdna Antibody

AbstractCD226 is an activating receptor expressed on the cell surface of natural killer cells and T cells. Although CD226 polymorphism is known to be involved in systemic lupus erythematosus (SLE), the involvement of soluble CD226 (sCD226) in SLE is still unknown. In the present study, we measured serum sCD226 levels using an enzyme-linked immunosorbent assay in 58 SLE patients and 33 healthy controls (HCs) and evaluated their associations with SLE Disease Activity Index 2000 (SLEDAI-2K), clinical manifestations, laboratory data, and the cumulative probability of flare. Serum sCD226 levels showed no significant differences between SLE patients and HCs. However, sCD226 levels were significantly elevated in active SLE patients with a SLEDAI-2K score of ≥ 20 compared with HCs. In SLE patients, sCD226 levels were significantly correlated with SLEDAI-2K scores and anti-dsDNA antibody titers. Moreover, the cumulative probability of flare was markedly higher in patients with high sCD226 than in those with low sCD226. In patients with neuropsychiatric involvement, sCD226 levels were elevated and reflected neuropsychiatric disease activity. These findings indicate that serum sCD226 levels are associated with disease activity and flares of SLE. Thus, it may be a useful biomarker for SLE, and its monitoring allows for more precise SLE management.

Elevated Serum Levels of Syndecan-1 Are Associated with Renal Involvement in Patients with Systemic Lupus Erythematosus

2014 ◽  
Vol 42 (2) ◽  
pp. 202-209 ◽  
Author(s):  
Ki-Jo Kim ◽  
Ji-Young Kim ◽  
In-Woon Baek ◽  
Wan-Uk Kim ◽  
Chul-Soo Cho
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Elevated Serum ◽  
Clinical Manifestations ◽  
Major Constituent ◽  
Systemic Lupus ◽  
Filtration Barrier ◽  
Dsdna Antibody

Objective.Syndecan-1 (SDC-1) is a major constituent of the endothelial glycocalyx, which plays a role in maintaining vascular homeostasis and functions as a glomerular filtration barrier. SDC-1 is readily shed into the blood under various conditions, but the clinical implication of circulating SDC-1 in patients with systemic lupus erythematosus (SLE) remains unclear. We aimed to investigate the association of serum SDC-1 level with certain clinical manifestations of SLE.Methods.We measured serum SDC-1 levels by ELISA in 111 patients with SLE, 18 with rheumatoid arthritis (RA), and 20 healthy subjects, and investigated its association with clinical manifestations and laboratory variables.Results.Serum SDC-1 levels were higher in patients with SLE than in those with RA and healthy controls (both p < 0.001) and were positively correlated with SLE Disease Activity Index (SLEDAI; r = 0.367, p < 0.001) and anti-dsDNA antibody level (r = 0.259, p = 0.007), but inversely correlated with serum C3 and CH50 levels (r = −0.305, p = 0.001 and r = −0.244, p = 0.012). Patients with active nephritis had higher serum SDC-1 levels than patients with inactive nephritis and those without nephritis (both p < 0.001). In addition, serum SDC-1 levels were correlated with renal SLEDAI score (r = 0.540, p < 0.001) and excretion of proteinuria as measured by spot urine protein/creatinine ratio (r = 0.538, p < 0.001). In 14 patients with lupus nephritis (LN) whose serum samples were obtained at the time of renal biopsy, there was a positive correlation between serum SDC-1 levels and activity index (r = 0.632, p = 0.015).Conclusion.Serum SDC-1 levels are increased in SLE patients with nephritis, indicating that SDC-1 might be a useful serum biomarker for active LN.

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

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.

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

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.

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 THU0017 ATTEMPTS TO LINK EXONIC GENE POLYMORPHISMS TO SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)-ASSOCIATED PROTEIN MODIFIED FUNCTIONALITY: A STRUCTURAL BIOLOGY APPROACH

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 221.1-222
Author(s):  
E. Eliopoulos ◽  
G. Goulielmos ◽  
M. Matalliotakis ◽  
D. Vlachakis ◽  
T. Niewold ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Protein Structure ◽  
Molecular Modeling ◽  
Nucleic Acid ◽  
Molecular Mechanics ◽  
Lupus Erythematosus ◽  
Gene Polymorphisms ◽  
Association Studies ◽  
Systemic Lupus ◽  
Molecular Graphics

Background:Gene association studies and genome wide association studies (GWAS) have played a primary role in depicting genetic contributions to systemic lupus erythematosus (SLE) development, while accommodating the exonic polymorphisms on the protein structure level, when available, enhances our understanding of protein function modification or depletion. Linking human genetics with therapeutic targets requires the biological function of the causal gene and variant to be known.Objectives:To investigate recently identified SLE-associated functional gene polymorphisms, such asPARP1,ITGAM, TNFAIP3, NCF1, PON1, IFIH1, SH2B3andTYK2[1-4] by correlation to protein structure and function.Methods:Three-dimensional (3D) homology modeling and molecular mechanics/dynamics studies were applied for the localization of the polymorphisms under study on the respective proteins. The mutants were constructed using molecular modeling with the program Maestro (Schrodinger, LLC), which was also used to analyze the conformational changes caused by the mutation. All figures depicting 3D models were created using the molecular graphics program PyMOL V.2.2 [5].Results:Modeling revealed that rs1136410 SNP encodes the less common polymorphism Val762Ala onPARP1that reduces enzymatic activity of Poly(ADP-ribose) polymerase 1 (Figure 1),ITGAMpolymorphism rs1143679 (Arg77His) on Integrin alpha M, component of the macrophage-1 antigen complex affects protein surface recognition,TNFAIP3rs2230926 polymorphism encodes Cys instead of Phe at residue 127 of the ubiquitin editing A20 protein, while rs201802880 polymorphism of the neutrophil cytosolic factor 1 (NCF1) gene modifies the function of the cytosolic subunit of neutrophil NADPH oxidase with the mutation Arg90His.PON1is involved in the oxidative stress process that cause tissue damage observed in SLE and anti-phospholipid syndrome (APS). ThePON1Gln192Arg mutation (rs662 SNP) affects shape and recognition of the ligand recognition site as part of the evolutionary process, whileIFIH1(rs35667974) helicase C domain1 mutant I923V is located on an essential RNA beta loop interacting directly with the nucleic acid (Figure 2). Finally, the rs3184504 SNP ofSH2B3gene generates mutant Arg262Trp on SH2 adapter protein 3, acting as a signaling pathway involved in autoimmune disorders, while inTYK2 gene, one of the Janus kinases, the rs35018800 producing mutant Ala928Val modifies the ADP binding site.Figure 1.Details of the Val762 interaction where V762A mutation occurs in PARP1protein.Figure 2.Nucleic acid interacting IFIH1 helicase beta-loop where I923V mutation occurs (in purple).Conclusion:Based on several examples, we have tried to define a rational link from SLE-associated gene polymorphisms to structure and to modified function, including metagenomic analysis of SNPs, protein crystallography, protein molecular modeling, molecular mechanics and dynamics. Locating, shaping and understanding the target protein interaction interface plays a decisive role in most cases and provides clues for further pharmacological or medical actions [6].References:[1]Hur JW et al (2006). Rheumatology 45:711-7[2]Maiti AK et al (2014). Hum Mol Genet 23:4161-76[3]Shimane K et al (2010). Arthritis Rheum. 62:574-9[4]Linge P et al (2019). Ann Rheum Dis. 2019 Nov 8. pii: annrheumdis-2019-215820[5]Schrödinger LLC: The PyMOL Molecular Graphics System 2016 version 2.2. Available from: pymol.org/2/support.html[6]Plenge RM et al (2013). Nat Rev Drug Discov 12:581–94Disclosure of Interests:None declared

scholarly journals Sustained high expression of multiple APOBEC3 cytidine deaminases in systemic lupus erythematosus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Danielle Perez-Bercoff ◽  
Hélène Laude ◽  
Morgane Lemaire ◽  
Oliver Hunewald ◽  
Valérie Thiers ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cell Death ◽  
Lupus Erythematosus ◽  
Immunosuppressive Treatment ◽  
Elevated Serum ◽  
Serum Levels ◽  
Chronic Inflammatory Disease ◽  
Mrna Levels ◽  
Systemic Lupus ◽  
Inflammatory Conditions

AbstractAPOBEC3 (A3) enzymes are best known for their role as antiviral restriction factors and as mutagens in cancer. Although four of them, A3A, A3B, A3F and A3G, are induced by type-1-interferon (IFN-I), their role in inflammatory conditions is unknown. We thus investigated the expression of A3, and particularly A3A and A3B because of their ability to edit cellular DNA, in Systemic Lupus Erythematosus (SLE), a chronic inflammatory disease characterized by high IFN-α serum levels. In a cohort of 57 SLE patients, A3A and A3B, but also A3C and A3G, were upregulated ~ 10 to 15-fold (> 1000-fold for A3B) compared to healthy controls, particularly in patients with flares and elevated serum IFN-α levels. Hydroxychloroquine, corticosteroids and immunosuppressive treatment did not reverse A3 levels. The A3AΔ3B polymorphism, which potentiates A3A, was detected in 14.9% of patients and in 10% of controls, and was associated with higher A3A mRNA expression. A3A and A3B mRNA levels, but not A3C or A3G, were correlated positively with dsDNA breaks and negatively with lymphopenia. Exposure of SLE PBMCs to IFN-α in culture induced massive and sustained A3A levels by 4 h and led to massive cell death. Furthermore, the rs2853669 A > G polymorphism in the telomerase reverse transcriptase (TERT) promoter, which disrupts an Ets-TCF-binding site and influences certain cancers, was highly prevalent in SLE patients, possibly contributing to lymphopenia. Taken together, these findings suggest that high baseline A3A and A3B levels may contribute to cell frailty, lymphopenia and to the generation of neoantigens in SLE patients. Targeting A3 expression could be a strategy to reverse cell death and the generation of neoantigens.

scholarly journals New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond

2020 ◽  
Vol 9 (3) ◽  
pp. 712 ◽  
Author(s):  
Erkan Demirkaya ◽  
Sezgin Sahin ◽  
Micol Romano ◽  
Qing Zhou ◽  
Ivona Aksentijevich
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Current Knowledge ◽  
Association Studies ◽  
Severe Disease ◽  
Genetic Diagnosis ◽  
Genome Wide Association Studies ◽  
Systemic Lupus ◽  
Degree Relative ◽  
Adult Age

Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it’s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes.

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