scholarly journals Antiphospholipid Antibody Profiles and Thrombotic Outcomes in the Starlet Cohort of Patients with Systemic Lupus Erythematosus

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2126-2126
Author(s):  
Alistair Murray ◽  
Eric J. Campbell ◽  
Ann E. Clarke ◽  
Megan R.W. Barber ◽  
Tania Pannu ◽  
...  
Keyword(s):  
Decision Making ◽  
Multivariate Analysis ◽  
Lupus Erythematosus ◽  
Thrombotic Event ◽  
Individual Risk ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Superficial Vein Thrombosis ◽  
First Time

Abstract Introduction Antiphospholipid syndrome (APS) is an autoimmune condition characterized by the presence of antiphospholipid antibodies (aPL) and clinical outcomes of thrombosis and obstetric morbidity. APS is more common in patients with systemic lupus erythematous (SLE), with persistently positive aPLs being found in 20-30% of SLE patients. The revised Sapporo lab criteria for APS includes one or more of a positive lupus anticoagulant (LAC), anti-beta 2 glycoprotein 1 (aβ2GP1), or anticardiolipin (aCL). Antibodies must be persistently positive at >99 th percentile over at least 12 weeks (Miyakis et al. J Thromb Haemost, 2006). IgG anti-phosphatidylserine/prothrombin complex (aPS/PT), IgM aPS/PT, and IgG anti-domain 1β2GP1 (aD1β2GP1) are novel aPLs that have been associated with thrombosis, however, conclusive data is still lacking, and it remains unclear how best to incorporate these novel autoantibodies into clinical decision making. The aims of this study were to assess whether the non-criteria IgG aPS/PT, IgM aPS/PT, or IgG aD1 β2GP1 were associated with an increased risk of a first-time thrombotic event in SLE patients. By better understanding the risk of thrombosis in patients with novel aPLs, independent of their association with established criteria aPLs, we can better counsel patients on individual risk of thrombosis. Methods A retrospective chart review was performed on all participants enrolled in the SouThern Alberta Registry for Lupus EryThematosus (STARLET) database. STARLET is a prevalent cohort of 348 adult patients fulfilling American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) classification criteria for SLE. Serology results for LAC, IgG aCL, IgG aβ2GP1, IgG aPS/PT, IgM aPS/PT, and IgG aD1β2GP1 were recorded over the patient's disease course. Anti-PS/PT antibodies were measured by an enzyme-linked immunosorbent assay and IgG aD1β2GP1 by a chemiluminescence immunoassay. Electronic medical records were reviewed from March 2006 to January 2021 for first-time objectively confirmed venous, arterial, and small vessel thrombotic events, as defined by the revised Sapporo criteria. Libman-Sacks endocarditis, livedo reticularis, superficial vein thrombosis and transient ischemic attacks were not included as thrombotic events. Discrepancies in outcomes were resolved by consensus. Results Among patients in the STARLET database, 91.8% were women, 65.5% were White, and the mean age was 42.7 (SD 15). Of 348 patients, 60 (17%) met the revised Sapporo lab criteria, and of those 30 (50%) had a thrombotic event. Among patients who met the revised Sapporo lab criteria, there was an increased risk of thrombosis (OR 3.7, 95% CI, 2.1-6.6). Among the 143 patients that had at least one positive non-criteria autoantibody, 46 (32.2%) had a thrombotic event (OR 1.6, 95% CI 0.97-2.6) (Table 1). Univariate analysis for the association between each non-criteria antibody type and thrombosis are presented in Table 1. There were statistically significant correlations between the revised Sapporo criteria aPLs and non-criteria aPLs; the IgG aPS/PT had a stronger correlation to LAC (Spearman=0.47) than the IgM aPS/PT (Spearman=0.38) (Table 2). In a multivariate analysis that controlled for age, sex, and meeting the revised Sapporo lab criteria, only the non-criteria antibody IgG aPS/PT was associated with an increased risk of thrombosis with an OR of 2.8 (95% CI, 1.3-6.0) (Table 3). There were 35 patients in our cohort that did not meet revised Sapporo lab criteria that had a positive IgG aPS/PT and of these patients 8 (22.9%) had a thrombotic event. Conclusions In this cohort of SLE patients, IgG aPS/PT and IgG aD1 β2GP1 were associated with an increased risk of thrombosis, and both antibodies were correlated with previously established aPLs. In our multivariate analysis, only the IgG aPS/PT non-criteria antibody was associated with an increased risk of thrombosis, independent of revised Sapporo criteria aPLs, with an OR of 2.8 (95% CI, 1.3-6.0). Not all patients in the STARLET database had non-criteria aPL autoantibodies measured, and so a smaller sample size may have affected our ability to detect associations with thrombosis. Given the limited data in the area, this valuable information can help inform clinician and patient decision making and provide further guidance on the role of non-criteria antibody testing for patients with SLE. Figure 1 Figure 1. Disclosures Barber: AbbVie: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; GlaxoSmithKline: Consultancy, Honoraria; Sanofi Genzyme: Consultancy, Honoraria. Fritzler: MitogenDx Laboratory: Current Employment; Werfen International: Consultancy; Aesku Group: Consultancy; Alexion Canada: Consultancy. Skeith: CSL Behring: Research Funding; Leo Pharma: Honoraria; Sanofi: Honoraria.

scholarly journals The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus

Reumatismo ◽  
2016 ◽  
Vol 68 (3) ◽  
pp. 137 ◽  
Author(s):  
M. Taraborelli ◽  
M.G. Lazzaroni ◽  
N. Martinazzi ◽  
M. Fredi ◽  
I. Cavazzana ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Multivariate Analysis ◽  
Lupus Erythematosus ◽  
Antiphospholipid Antibodies ◽  
Valvular Disease ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Clinically Significant ◽  
Cutaneous Lupus

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- β2Glycoprotein I IgG/IgM &gt;99<sup>th</sup> percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher’s exact test for categorical variables and Student’s <em>t</em> or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values &lt;0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p&lt;0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p&lt;0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p&lt;0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS.

Plasma interleukin-22 level, variants in interleukin-22 gene polymorphism, and the severity of systemic lupus erythematosus among Egyptian pediatric and adolescents

Lupus ◽  
2021 ◽  
pp. 096120332110423
Author(s):  
Zeinab R Attia ◽  
Mohamed M Zedan ◽  
Thuraya M Mutawi ◽  
Entsar A Saad ◽  
Mohamed A El Basuni
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Regression Analysis ◽  
Gene Polymorphism ◽  
Lupus Erythematosus ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Interleukin 22 ◽  
Increased Risk ◽  
Significant Difference ◽  
First Time

Objectives Our purpose was to investigate, for the first time, genotypes and alleles distribution of two single nucleotide polymorphisms (SNPs) of interleukin 22 (IL-22) (rs1012356 and rs2227485) in Egyptian pediatric and adolescents with systemic lupus erythematosus (SLE) and to evaluate the plasma IL-22 levels and their association with gene polymorphism and SLE risk and severity. Methods The TaqMan™ SNP genotyping assay on a real-time polymerase chain reaction (PCR) system was employed to evaluate the polymorphism’s genotypes. Plasma IL-22 levels were determined by using an enzyme-linked immunoabsorbent assay (ELISA). Results The frequencies and genotypes of rs2227485 and rs1012356 in IL-22 between SLE patients and controls also haplotypes formed by the same SNPs revealed no statistically significant difference ( p > 0.05). Otherwise, logistic regression analysis revealed that patients carrying rs1012356 “TA + AA” genotype had increased risk for prediction of SLE activity (OR = 1.610, 95% CI = 1.339–2.760, p = 0.034) by lowering plasma IL-22 level. Conclusions Among Egyptian pediatric and adolescents, we confirm a combined model “TA + AA” in rs1012356 (A/T) of IL-22 in regression analysis, as an independent predictor for SLE activity by lowering IL-22 plasma levels. Despite neither SNP rs2227485 A/G in IL-22 gene nor haplotypes formed by the same two SNPs (rs2227485 A/G and rs1012356 A/T) were significantly associated with the clinical and/or laboratory manifestations of SLE.

Synergistic effect of cumulative corticosteroid dose and immunosuppressants on avascular necrosis in patients with systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1644-1651 ◽  
Author(s):  
H H Kwon ◽  
S Y Bang ◽  
S Won ◽  
Y Park ◽  
J H Yi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Avascular Necrosis ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Individual Risk ◽  
High Dose ◽  
Systemic Lupus ◽  
Corticosteroid Dose ◽  
Increased Risk

Objectives Avascular necrosis (AVN) is one of the most common causes of organ damage in patients with systemic lupus erythematosus (SLE) and often causes serious physical disability. The aims of this study were to investigate clinical risk factors associated with symptomatic AVN and to analyze their synergistic effects in a large SLE cohort in Korea. Methods Patients with SLE were enrolled and followed from 1998 to 2014 in the Hanyang BAE Lupus cohort, and damage was measured annually according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). AVN was confirmed by imaging study if patients had symptoms. To determine risk factors for AVN, clinical, laboratory and therapeutic variables were analyzed by logistic regression. Relative excess risk due to interaction (RERI), attributable proportion (AP), and synergy index (S) were calculated to measure interactions between significant variables. Results Among 1219 SLE patients, symptomatic AVN was the most common type of musculoskeletal damage (10.8%, n = 132). SLE patients with AVN showed an earlier onset age, demonstrated AVN more commonly in conjunction with certain other clinical manifestations such as renal and neuropsychiatric disorders, and received significantly higher total cumulative corticosteroid dose and immunosuppressive agents than did patients without AVN. However, in multivariable analysis, only two variables including use of a cumulative corticosteroid dose greater than 20 g (odds ratio (OR) 3.62, p = 0.015) and use of immunosuppressants including cyclophosphamide or mycophenolate mofetil (OR 4.51, p < 0.001) remained as significant risk factors for AVN. Patients with cumulative corticosteroid dose > 20 g and immunosuppressant use had a 15.44-fold increased risk for AVN, compared with patients without these risk factors ( p < 0.001). RERI, AP and S, which define the strength of interactions between two risk factors, were 9.01 (95% confidence interval (CI) 1.30–16.73), 0.58 (95% CI 0.36–0.81) and 2.66 (95% CI 1.42–4.99), respectively, supporting the presence of synergistic interactions in the development of symptomatic AVN in our Korean lupus cohort. Conclusions An individual risk assessment for AVN development should be made prior to and during treatment for SLE, especially in patients with high-dose corticosteroid and immunosuppressant use regardless of clinical manifestations and disease activity.

Longterm Hydroxychloroquine Therapy and Low-dose Aspirin May Have an Additive Effectiveness in the Primary Prevention of Cardiovascular Events in Patients with Systemic Lupus Erythematosus

2017 ◽  
Vol 44 (7) ◽  
pp. 1032-1038 ◽  
Author(s):  
Serena Fasano ◽  
Luciana Pierro ◽  
Ilenia Pantano ◽  
Michele Iudici ◽  
Gabriele Valentini
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Low Dose ◽  
Thrombotic Event ◽  
Systemic Lupus ◽  
Cox Regression Analysis ◽  
Dose Aspirin ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Low Dose Aspirin

Objective.Systemic lupus erythematosus (SLE) is associated with an increased risk of cardiovascular disease (CVD). Thromboprophylaxis with low-dose aspirin (ASA) and hydroxychloroquine (HCQ) seems promising in SLE. We investigated the effects of HCQ cumulative dosages (c-HCQ) and the possible synergistic efficacy of ASA and HCQ in preventing a first CV event (CVE) in patients with SLE.Methods.Patients consecutively admitted to our center who, at admission, satisfied the 1997 American College of Rheumatology and/or 2012 Systemic Lupus Collaborating Clinics classification criteria for SLE, and had not experienced any CVE, were enrolled. The occurrence of a thrombotic event, use of ASA, and c-HCQ were recorded. Kaplan-Meier analysis was performed to determine the c-HCQ associated with a lower incidence of CVE. Cox regression analysis served to identify factors associated with a first CVE.Results.For the study, 189 patients with SLE were enrolled and monitored for 13 years (median). Ten CVE occurred during followup. At Kaplan-Meier analysis, the CVE-free rate was higher in ASA-treated patients administered a c-HCQ > 600 g (standard HCQ dose for at least 5 yrs) than in patients receiving ASA alone, or with a c-HCQ dose < 600 g (log-rank test chi-square = 4.01, p = 0.04). Multivariate analysis showed that antimalarials plus ASA protected against thrombosis (HR 0.041 and HR 0.047, respectively), while antiphospholipid antibodies (HR 17.965) and hypertension (HR 18.054) increased the risk of a first CVE.Conclusion.Our results suggest that prolonged use of HCQ plus ASA is thromboprotective in SLE and provides additional evidence for its continued use in patients with SLE.

scholarly journals Association of Melatonin Pathway Gene’s Single-Nucleotide Polymorphisms with Systemic Lupus Erythematosus in a Chinese Population

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Peng Wang ◽  
Lei Liu ◽  
Li-Fang Zhao ◽  
Chan-Na Zhao ◽  
Yan-Mei Mao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Single Nucleotide Polymorphisms ◽  
Genetic Association ◽  
Lupus Erythematosus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Nucleotide Polymorphisms ◽  
Systemic Lupus ◽  
Single Nucleotide ◽  
Increased Risk ◽  
Significant Difference

Objectives. This study was to investigate the association of melatonin (MTN) pathway gene’s single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE). Methods. We recruited 495 SLE patients and 493 healthy controls, 11 tag SNPs in MTN receptor 1a (MTNR1a), MTNR1b, and arylalkylamine N-acetyltransferase (AANAT) genes were genotyped and analyzed. Serum MTN concentration was determined by enzyme-linked immunosorbent assay (ELISA) kits. Results. Two SNPs of AANAT gene (rs8150 and rs3760138) associated with the risk of SLE; CC carriers of rs8150 had a lower risk as compared to GG (OR=0.537, 95% CI: 0.361, 0.799), whereas GG carrier in rs3760138 had an increased risk (OR=1.823, 95% CI: 1.154, 2.880) compared to TT. However, we did not find any genetic association between the other nine SNPs with SLE risk. Case-only analysis showed associations of rs2165667 and rs1562444 with arthritis, rs10830962 with malar rash, rs3760138 with immunological abnormality, and rs8150 with hematological abnormality. Furthermore, a significant difference between plasma MTN levels with different genotypes of rs1562444 was observed. Haplotype analyses revealed that haplotype of CCTAT, CTAGT, and GGG was significantly associated with the increased risk in SLE susceptibility, but TCTAT and CTG appeared to be a protective haplotype. Conclusions. The present study supported the genetic association of MTN pathway genes with SLE susceptibility and specific clinical manifestations, suggesting the potential role of MTN pathway genes in the pathogenesis and development of SLE.

Urine β-2-glycoprotein 1 as a biomarker for diagnosis of systemic lupus erythematosus

Lupus ◽  
2021 ◽  
pp. 096120332110142
Author(s):  
Jung Sun Lee ◽  
Eun-Ju Lee ◽  
Jeonghun Yeom ◽  
Ji Seon Oh ◽  
Seokchan Hong ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Medical Center ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Diagnostic Value ◽  
Urine Samples ◽  
Enzyme Linked Immunosorbent Assay ◽  
Systemic Lupus ◽  
Asan Medical

Objective The need for a biomarker with robust sensitivity and specificity in diagnosing systemic lupus erythematosus (SLE) remains unmet. Compared with blood samples, urine samples are more easily collected; thus, we aimed to identify such a biomarker based on urinary proteomics which could distinguish patients with SLE from healthy controls (HCs). Methods Urine samples were collected from 76 SLE patients who visited rheumatology clinic in 2019 at Asan medical center and from 25 HCs. Urine proteins were analyzed using sequential windowed acquisition of all theoretical fragment ion spectra-mass spectrometry, and the candidate marker was confirmed by enzyme-linked immunosorbent assay (ELISA). Receiver operating characteristic curve analysis was used to determine the diagnostic value of the candidate biomarker. Results Of 1157 proteins quantified, 153 were differentially expressed in urine samples from HCs. Among them were previously known markers including α-1-acid glycoprotein 1, α-2-HS-glycoprotein, ceruloplasmin, and prostaglandin-H2 D-isomerase. Moreover, the amount of β-2 glycoprotein (APOH) was increased in the urine of patients with SLE. The ELISA results also showed the level of urine APOH was higher in patients with SLE than in HCs and patients with rheumatoid arthritis. Moreover, the level was not different between SLE patients with and without nephritis. The urine APOH had an area under the curve value of 0.946 at a cut-off value of 228.53 ng/mg (sensitivity 91.5%, specificity 92.0%) for the diagnosis of SLE. Conclusion The results indicate that the urine APOH level can be an appropriate screening tool in a clinical setting when SLE is suspected.

scholarly journals Phase 1 double-blind randomized safety trial of the Janus kinase inhibitor tofacitinib in systemic lupus erythematosus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sarfaraz A. Hasni ◽  
Sarthak Gupta ◽  
Michael Davis ◽  
Elaine Poncio ◽  
Yenealem Temesgen-Oyelakin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Kinase Inhibitor ◽  
Janus Kinase ◽  
Controlled Clinical Trial ◽  
Type I ◽  
Systemic Lupus ◽  
Double Blind ◽  
Premature Cardiovascular Disease ◽  
Increased Risk

AbstractIncreased risk of premature cardiovascular disease (CVD) is well recognized in systemic lupus erythematosus (SLE). Aberrant type I-Interferon (IFN)-neutrophil interactions contribute to this enhanced CVD risk. In lupus animal models, the Janus kinase (JAK) inhibitor tofacitinib improves clinical features, immune dysregulation and vascular dysfunction. We conducted a randomized, double-blind, placebo-controlled clinical trial of tofacitinib in SLE subjects (ClinicalTrials.gov NCT02535689). In this study, 30 subjects are randomized to tofacitinib (5 mg twice daily) or placebo in 2:1 block. The primary outcome of this study is safety and tolerability of tofacitinib. The secondary outcomes include clinical response and mechanistic studies. The tofacitinib is found to be safe in SLE meeting study’s primary endpoint. We also show that tofacitinib improves cardiometabolic and immunologic parameters associated with the premature atherosclerosis in SLE. Tofacitinib improves high-density lipoprotein cholesterol levels (p = 0.0006, CI 95%: 4.12, 13.32) and particle number (p = 0.0008, CI 95%: 1.58, 5.33); lecithin: cholesterol acyltransferase concentration (p = 0.024, CI 95%: 1.1, −26.5), cholesterol efflux capacity (p = 0.08, CI 95%: −0.01, 0.24), improvements in arterial stiffness and endothelium-dependent vasorelaxation and decrease in type I IFN gene signature, low-density granulocytes and circulating NETs. Some of these improvements are more robust in subjects with STAT4 risk allele.

FRI0516 FACTORS ASSOCIATED WITH DECREASED CERVICAL CANCER SCREENING IN WOMEN WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 857.1-857
Author(s):  
S. Bruera ◽  
R. Zogala ◽  
X. Lei ◽  
X. Pundole ◽  
H. Zhao ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Cervical Cancer ◽  
Cancer Screening ◽  
Autoimmune Disease ◽  
Cervical Cancer Screening ◽  
Lupus Erythematosus ◽  
Screening Rate ◽  
Systemic Lupus ◽  
Comorbidity Score ◽  
Increased Risk

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that carries an increased risk for both viral illnesses and malignancies, including a greater risk for both human papilloma virus (HPV) infection and cervical cancer. Due to this increased risk, the American Society of Colposcopy and Cervical Pathology guidelines for SLE patients recommend more frequent cervical cancer screening. Few studies have examined patient characteristics associated with decreased cervical cancer screening in patients with autoimmune disease, specifically SLE.Objectives:To estimate cervical cancer screening rates in women with recently diagnosed SLE, and to identify characteristics associated with decreased screening.Methods:We identified women with an initial diagnosis of SLE in the United States MarketScan Commercial Claims and Encounter (CCAE, age 18-64) administrative claims database. We included patients with at least three claims with a lupus diagnosis (first and last at least >90 days apart), no lupus claims within the year before initial claim, and who had been on antimalarial drugs for at least 90 days. We excluded all patients with a previous claim for hysterectomy.Cervical cancer screening was ascertained using diagnosis and procedure codes within 1 year before and 2 years after the first SLE claim. Our covariates included the year of first SLE claim (2001-2014), age at first SLE claim, comorbidity score, insurance type, geographical region, and prescriptions for multiple types of corticosteroids. Control patients included age-matched females without autoimmune disease. Univariate comparison and multivariate logistic regression models were built to evaluate determinants of screening.Results:We included 4,316 SLE patients (median age 45) and 86,544 control patients. The screening rate in SLE patients was 73.4% vs 58.5% in the controls (P < 0.001). The screening rate was 71% in 2001, increased to 75% in 2004, then decreased to 70% in 2014 (trend P =0.005). In the multivariate model the following factors were associated with decreased cervical cancer screening: year of first SLE claim 2012-2014 versus 2001-2005 (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.53 – 0.84, P < 0.001); older age 61-64 versus 21-30 (OR 0.27, 95% CI 0.19 – 0.39, P < 0.001); comorbidity score of ≥2 versus <2 (OR 0.71, 95% CI 0.6 – 0.83, P < 0.001); and use of corticosteroids for ≥ 90 days versus <90 days (OR 0.73, 95% CI 0.59 – 0.9, P = 0.003). Insurance type and geographical region were not associated with cervical cancer screening.Conclusion:About three quarters of women with SLE underwent cervical cancer screening within 3 years of their first lupus claim, at higher rates than controls. However, there was a concerning downward trend in screening rates in recent years. In addition, higher risk populations for cervical cancer (older age, increased comorbidities, and longer duration of corticosteroids) had lower screening rates. These findings highlight the need to enhance education for healthcare providers to improve utilization of screening in women with SLE at high risk of cervical cancer.Disclosure of Interests:Sebastian Bruera: None declared, Richard Zogala: None declared, Xiudong Lei: None declared, Xerxes Pundole: None declared, Hui Zhao: None declared, Sharon Giordano: None declared, Jessica Hwang Grant/research support from: MERCK grant funding unrelated to SLE., Maria Suarez-Almazor: None declared

scholarly journals An Analytic Approach Using Candidate Gene Selection and Logic Forest to Identify Gene by Environment Interactions (G × E) for Systemic Lupus Erythematosus in African Americans

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 496 ◽  
Author(s):  
Bethany Wolf ◽  
Paula Ramos ◽  
J. Hyer ◽  
Viswanathan Ramakrishnan ◽  
Gary Gilkeson ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Secondhand Smoke ◽  
Gene Selection ◽  
Search Space ◽  
Higher Order ◽  
Candidate Snps ◽  
Systemic Lupus ◽  
Increased Risk ◽  
Main Effects

Development and progression of many human diseases, such as systemic lupus erythematosus (SLE), are hypothesized to result from interactions between genetic and environmental factors. Current approaches to identify and evaluate interactions are limited, most often focusing on main effects and two-way interactions. While higher order interactions associated with disease are documented, they are difficult to detect since expanding the search space to all possible interactions of p predictors means evaluating 2p − 1 terms. For example, data with 150 candidate predictors requires considering over 1045 main effects and interactions. In this study, we present an analytical approach involving selection of candidate single nucleotide polymorphisms (SNPs) and environmental and/or clinical factors and use of Logic Forest to identify predictors of disease, including higher order interactions, followed by confirmation of the association between those predictors and interactions identified with disease outcome using logistic regression. We applied this approach to a study investigating whether smoking and/or secondhand smoke exposure interacts with candidate SNPs resulting in elevated risk of SLE. The approach identified both genetic and environmental risk factors, with evidence suggesting potential interactions between exposure to secondhand smoke as a child and genetic variation in the ITGAM gene associated with increased risk of SLE.

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