A polymorphism upstream MIR1279 gene is associated with pericarditis development in Systemic Lupus Erythematosus and contributes to definition of a genetic risk profile for this complication

Lupus ◽  
2016 ◽  
Vol 26 (8) ◽  
pp. 841-848 ◽  
Author(s):  
C Ciccacci ◽  
C Perricone ◽  
C Politi ◽  
S Rufini ◽  
F Ceccarelli ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Genetic Risk ◽  
Risk Profile ◽  
Systemic Lupus ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Profile Model ◽  
Risk Alleles ◽  
Definition Of ◽  
Gene Variability

Recently, a study has shown that a polymorphism in the region of MIR1279 modulates the expression of the TRAF3IP2 gene. Since polymorphisms in the TRAF3IP2 gene have been described in association with systemic lupus erithematosus (SLE) susceptibility and with the development of pericarditis, our aim is to verify if the MIR1279 gene variability could also be involved. The rs1463335 SNP, located upstream MIR1279 gene, was analyzed by allelic discrimination assay in 315 Italian SLE patients and 201 healthy controls. Moreover, the MIR1279 gene was full sequenced in 50 patients. A case/control association study and a genotype/phenotype correlation analysis were performed. We also constructed a pericarditis genetic risk profile for patients with SLE. The full sequencing of the MIR1279 gene in patients with SLE did not reveal any novel or known variation. The variant allele of the rs1463335 SNP was significantly associated with susceptibility to pericarditis ( P = 0.017 and OR = 1.67). A risk profile model for pericarditis considering the risk alleles of MIR1279 and three other genes (STAT4, PTPN2 and TRAF3IP2) showed that patients with 4 or 5 risk alleles have a higher risk of developing pericarditis ( OR = 4.09 with P = 0.001 and OR = 6.04 with P = 0.04 respectively). In conclusion, we describe for the first time the contribution of a MIR1279 SNP in pericarditis development in patients with SLE and a genetic risk profile model that could be useful to identify patients more susceptible to developing pericarditis in SLE. This approach could help to improve the prediction and the management of this complication.

scholarly journals AB0006 GENETIC RISK PROFILE FOR PSORIATIC ARTHRITIS PREDISPOSITION IN ITALIAN PATIENTS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1038.1-1038
Author(s):  
M. S. Chimenti ◽  
C. Ciccacci ◽  
G. De Benedittis ◽  
A. Latini ◽  
P. Conigliaro ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Psoriatic Arthritis ◽  
Candidate Genes ◽  
Genetic Risk ◽  
Protective Role ◽  
Risk Profile ◽  
Joint Disease ◽  
Taqman Assay ◽  
Allelic Discrimination ◽  
Risk Alleles

Background:Psoriatic arthritis (PsA) is a chronic inflammatory joint disease typically associated with psoriasis and classified in the group of spondyloarthritis (1). The pathogenesis is based on an interplay of different genes interacting with several environmental factors including stress, trauma, infections, triggering an inflammatory response related to the activation of innate and acquired immunity in different tissues and organs (2). However, the risk for the development of PsA is not clearly understood.Objectives:The aim of this study was to evaluate, in a cohort of Italian PsA out-patients of the Rheumatology Unit of the University of Rome Tor Vergata, the association of genetic variants in candidate genes for PSA susceptibility and their possible contribute in the modulation of clinical and laboratory features.Methods:The genes were selected according to previous studies describing these genes as involved in susceptibility to rheumatoid arthritis (RA) (3), since a common genetic background can be shared between these diseases. Nine SNPs (single nucleotide polymorphism) in eight candidate genes were analysed: STAT4 (rs7574865), TRAF3IP2 (rs33980500), TNFAIP3 (rs6920220 and rs2230926), MIR146A (rs2910164), PSORS1C1 (rs2233945), IL-10 (rs1800872), HCP5 (rs3099844) and ERAP1 (rs27524). Polymorphisms were analysed in 163 consecutive PsA out-patients and 198 healthy controls (HC). Genotyping was performed by allelic discrimination by TaqMan assay. Alleles frequencies differences between cases and controls or between phenotypic groups were compared using Pearson’s χ 2 test.Results:We have observed an association between PSA susceptibility and the variant alleles of STAT4 [OR= 1.60 (1.15-2.21), P= 0.005], TRAF3IP2 [OR= 1.65 (1.01-2.65), P= 0.04], ERAP1 [OR= 1.40 (1.05-1.85), P= 0.02] and TNFAIP3 (rs6920220) [OR= 1.75 (1.19-2.57), P= 0.004]. On the contrary, the variant allele of IL-10 polymorphism seems to play a protective role [OR= 0.74 (1.05-1.85), P= 0.05]. Moreover, in order to define a genetic risk profile, we have counted the total number of risk alleles in each subject, considering as risk alleles the allelic variant of rs7574865 (STAT4), rs33980500 (TRAF3IP2), rs6920220 (TNFAIP3) and rs27524 (ERAP1) SNPs. Then, we have compared the risk allele number distribution between patients and HC (Fig.1). Classes with 3 or more risk alleles are significantly more represented in patients than in HC (OR= 2.03, P=0.004). The risk to develop the disease increases significantly in subjects with at least four risk alleles (OR= 2.96, P=0.002).Figure 1.Number of risk alleles in patients and controls: rs7574865 (STAT4), rs33980500 (TRAF3IP2), rs6920220 (TNFAIP3) and rs27524 (ERAP1) SNPs.Conclusion:We confirm the associations between five SNPs, already studied in RA, and PSA susceptibility, suggesting a common inflammatory pathway in chronic inflammatory rheumatological diseases. Moreover, we show how the genotyping of only few associated SNPs could help to define a genetic risk profile for PSA development.References:[1]Calabresi E, et al. One year in review 2019: psoriatic arthritis. Clin Exp Rheumatol. 2020;38:1046-55.[2]Chimenti MS, Triggianese P, De Martino E, Conigliaro P, Fonti GL, Sunzini F, Caso F, Perricone C, Costa L, Perricone R. An update on pathogenesis of psoriatic arthritis and potential therapeutic targets. Expert Rev Clin Immunol. 2019 Aug;15(8):823-836.[3]Ciccacci C, et al. Polymorphisms in STAT-4, IL-10, PSORS1C1, PTPN2 and MIR146A genes are associated differently with prognostic factors in Italian patients affected by rheumatoid arthritis. Clin Exp Immunol. 2016;186:157-63.Disclosure of Interests:None declared

scholarly journals TNFAIP3 Gene Polymorphisms in Three Common Autoimmune Diseases: Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Primary Sjogren Syndrome—Association with Disease Susceptibility and Clinical Phenotypes in Italian Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
C. Ciccacci ◽  
A. Latini ◽  
C. Perricone ◽  
P. Conigliaro ◽  
S. Colafrancesco ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Systemic Lupus Erythematosus ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Variant Allele ◽  
Italian Population ◽  
Systemic Lupus ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Necrosis Factor Alpha

Autoimmune diseases (AIDs) are complex diseases characterized by persistent or recurrent inflammation, alteration of immune response, and production of specific autoantibodies. It is known that different AIDs share several susceptibility genetic loci. Tumor necrosis factor alpha inducible protein 3 (TNFAIP3) encodes the ubiquitin-modifying enzyme A20, which downregulates inflammation by restricting NF-κB, a transcription factor that regulates expression of various proinflammatory genes. Variants in TNFAIP3 gene have been described as associated with susceptibility to several AIDs. Here, we analyzed two TNFAIP3 polymorphisms in Italian patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and primary Sjogren’s syndrome (pSS), to verify if the genetic variability of TNFAIP3 gene is involved in genetic predisposition to AIDs also in the Italian population. We recruited 313 SLE patients, 256 RA patients, 195 pSS patients, and 236 healthy controls. Genotyping of rs2230926 and rs6920220 in TNFAIP3 gene was performed by an allelic discrimination assay. We carried out a case/control association study and a genotype/phenotype correlation analysis. A higher risk to develop SLE was observed for rs2230926 (P=0.02, OR=1.92). No association was observed between this SNP and the susceptibility to pSS or RA. However, the rs2230926 variant allele seems to confer a higher risk to develop lymphoma in pSS patients, while in RA patients, the presence of RF resulted significantly associated with the variant allele. Regarding the rs6920220 SNP, we observed a significant association of the variant allele with SLE (P=0.03, OR=1.53), pSS (P=0.016, OR=1.69), and RA (P=0.0001, OR=2.35) susceptibility. Furthermore, SLE patients carrying the variant allele showed a higher risk to develop pericarditis, pleurisy, and kidney complications. Our results support the importance of the TNFAIP3 gene variant role in the development of different autoimmune diseases in the Italian population and furtherly confirm a sharing of genetic predisposing factors among these three pathologies.

Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Enhances the Ability of SLE Responder Index to Identify Responders in Clinical Trials

2011 ◽  
Vol 38 (11) ◽  
pp. 2395-2399 ◽  
Author(s):  
ZAHI TOUMA ◽  
DAFNA D. GLADMAN ◽  
DOMINIQUE IBAÑEZ ◽  
SHAHRZAD TAGHAVI-ZADEH ◽  
MURRAY B. UROWITZ
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
Original Definition ◽  
Definition Of

Objective.To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders.Methods.Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician’s Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.Results.A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001).Conclusion.SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.

The Cancer Risk Profile of Systemic Lupus Erythematosus Patients

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Dylan Hardenbergh ◽  
Rakhi Naik ◽  
Rebecca Manno ◽  
Antoine Azar ◽  
Jose Manuel Monroy Trujillo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cancer Risk ◽  
Lupus Erythematosus ◽  
Risk Profile ◽  
Systemic Lupus

Lupus: the new epidemic

Lupus ◽  
2019 ◽  
Vol 28 (9) ◽  
pp. 1031-1050 ◽  
Author(s):  
M F Ugarte-Gil ◽  
L A González ◽  
G S Alarcón
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Secular Trends ◽  
Classification Criteria ◽  
Systemic Lupus ◽  
New Classification ◽  
Uniform Definition ◽  
Definition Of ◽  
Incomplete Lupus

Is systemic lupus erythematosus (SLE) is occurring more frequently now than in decades past? Despite improvements in the identification of patients with SLE, the development of new classification criteria, and the recognition of several biomarkers used alone or in combination, the diagnosis of SLE is still a challenge for clinicians, in particular early in the course of the disease, which makes the recognition of secular trends difficult to ascertain. Lacking a uniform definition of preclinical lupus or incomplete lupus, it is difficult to predict accurately which patients would go on to develop SLE. We will briefly review the classification criteria, early or preclinical SLE, the epidemiology of SLE, antinuclear antibodies-negative SLE, and biomarkers of the disease.

Sign in / Sign up

Export Citation Format

Share Document