Disease-specific quality of life in patients with lupus nephritis.

Background Patient-reported outcomes in lupus nephritis (LN) are not well studied. Studies with disease-targeted PRO tool in LN do not exist. Herein, we describe quality of life (QOL: HRQOL & non-HRQOL) among LN patients using LupusPRO. Methods International, cross-sectional data from 1259 patients with systemic lupus erythematosus (SLE) and LupusPRO were compared, stratified by (a) presence of LN (ACR classification criteria (ACR-LN)) at any time and, (b) active LN (on SLEDAI) at study visit. Damage was assessed by SLICC/ACR-SDI. Multivariate regression analyses for QOL against ACR-LN (active LN) after adjusting for age, gender, ethnicity and country of recruitment were performed. Results Mean (SD) age was 41.7 (13.5) yrs, 93% were women. Five hundred and thirty-nine of 1259 SLE patients had ACR-LN. ACR-LN group was younger, were more often on immunosuppressive medications, had worse QOL on lupus medications and procreation than non-ACR-LN patients. HRQOL and non-HRQOL scores were similar in both groups. One hundred and twenty-nine of 539 ACR-LN patients had active LN. Active LN group was younger, had greater disease activity and had worse HRQOL and non-HRQOL compared to patients without active LN. Specific domains adversely affected were lupus symptoms, lupus medications, procreation, emotional health, body image and desires-goals domains. Patients with ACR-LN and active LN fared significantly worse in lupus medications and procreation HRQOL domains, even after adjusting for age, ethnicity, gender and country of recruitment. Conclusions Lupus nephritis patients have poor QOL. Patients with active LN have worse HRQOL and non-HRQOL. Most domains affected are not included in the generic QOL tools used in SLE. LN patients must receive discussion on lupus medications and procreation issues. Patients with active LN need comprehensive assessments and addressal of QOL, along with treatment for active LN.

Breast cancer in systemic lupus erythematosus (SLE): receptor status and treatment.

Objective There is a decreased risk of breast cancer in systemic lupus erythematosus (SLE) versus the general population; little is known regarding the receptor status of breast cancers in SLE, or treatment. Methods Breast cancer cases occurring after SLE diagnosis were ascertained through linkage with tumor registries. We determined breast cancer positivity for estrogen receptors (ER), progesterone receptors (PR), and/or Human Epidermal Growth Factor Receptor 2 (HER2), as well as cancer treatment. Results We obtained information on ER, PR, and/or HER2 status for 63 SLE patients with breast cancer. Fifty-three had information on ER and/or PR status; 36 of these (69%) were ER positive. Thirty-six of the 63 had information on HER2 status; of these, 26 had complete information on all three receptors. Twenty-one of these 26 (81%) were HER2 negative; seven of 26(27%) were triple negative. All but one patient underwent surgery; 11.5% received both non-tamoxifen chemotherapy and radiotherapy, 16.4% radiotherapy without non-tamoxifen chemotherapy, and 14.7% received non-tamoxifen chemotherapy without radiotherapy. Conclusion ER positivity was similar to historical general population figures, with a trend toward a higher proportion of triple-negative breast cancers in SLE (possibly reflecting the relatively young age of our SLE patients).

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Breast cancer in systemic lupus.

Objective There is a decreased breast cancer risk in systemic lupus erythematosus (SLE) versus the general population. We assessed a large sample of SLE patients, evaluating demographic and clinical characteristics and breast cancer risk. Methods We performed case-cohort analyses within a multi-center international SLE sample. We calculated the breast cancer hazard ratio (HR) in female SLE patients, relative to demographics, reproductive history, family history of breast cancer, and time-dependent measures of anti-dsDNA positivity, cumulative disease activity, and drugs, adjusted for SLE duration. Results There were 86 SLE breast cancers and 4498 female SLE cancer-free controls. Patients were followed on average for 7.6 years. Versus controls, SLE breast cancer cases tended to be white and older. Breast cancer cases were similar to controls regarding anti-dsDNA positivity, disease activity, and most drug exposures over time. In univariate and multivariate models, the principal factor associated with breast cancers was older age at cohort entry. Conclusions There was little evidence that breast cancer risk in this SLE sample was strongly driven by any of the clinical factors that we studied. Further search for factors that determine the lower risk of breast cancer in SLE may be warranted.

Preventing the development of SLE: identifying risk factors and proposing pathways for clinical care.

Although challenging, developing evidence-based approaches to an early and accurate diagnosis of systemic lupus erythematosus is a key approach to preventing disease and lupus-associated morbidity and mortality. Advances in our understanding of preclinical and incomplete lupus erythematosus have enabled the identification of risk factors that may predict disease and the development of potential strategies aimed at primary prevention. Emerging data support the notion that there is a temporal disease progression from initial asymptomatic autoimmunity (preclinical lupus) through early clinical features of the disease (incomplete lupus erythematosus) to finally becoming fully classifiable systemic lupus erythematosus (complete lupus erythematosus). Here, we review the demographic, clinical, biomarker as well as genetic and environmental features that are reported to increase the risk of disease progression. Based on these risk factors, we propose a clinical care pathway for patients with early disease. We envisage that such a pathway, through early identification of disease, may improve patient outcomes, while reducing health care costs.

What investigations are needed to optimally monitor for malignancies in SLE?

OBJECTIVE: The overall cancer incidence risk in systemic lupus erythematosus (SLE) is approximately 15%-20% more than in the general population. Nevertheless, to date, the optimal malignancy screening measures in SLE remain undefined. Our objective is to determine what investigations are needed to optimally monitor for malignancies in SLE in order to inform upcoming Canadian Rheumatology Association recommendations. METHODS: We conducted a systematic search looking at three scientific sources, Embase, Medline and Cochrane, in an attempt to identify cancer screening recommendations for patients with SLE. We used a filter for observational studies and included articles published in 2000 and onward. RESULTS: The initial search strategy led to 986 records. After removal of duplicates and articles unrelated to SLE, we were left with 497 titles. From those, 79 research articles on cancer incidence in SLE were isolated and reviewed. Of the 79 original research papers, 25 offered screening recommendations, 14 suggested additional cancer screening whereas 11 studies simply promoted adherence to general population screening measures. The suggestions for more rigorous screening included recommending human papilloma virus testing in addition to routine cervical screening, and/or that cervical screening should be performed annually and/or suggested urine cancer screening in SLE patients with a history of cyclophosphamide exposure. CONCLUSIONS: We found no original research studies directly comparing cancer screening strategies in SLE. Generally, authors recommend adherence to general population screening measures, particularly cervical screening. This, possibly with adding targeted screening in special cases (e.g. annual urine cytology in patients with prior cyclophosphamide exposure, and considering existing lung cancer screening guidelines for past heavy smokers), may be a reasonable approach for cancer screening in SLE.

Anti-C1q antibodies in systemic lupus erythematosus.

OBJECTIVE: Anti-C1q has been associated with systemic lupus erythematosus (SLE) and lupus nephritis in previous studies. We studied anti-C1q specificity for SLE (vs rheumatic disease controls) and the association with SLE manifestations in an international multicenter study. METHODS: Information and blood samples were obtained in a cross-sectional study from patients with SLE (n = 308) and other rheumatologic diseases (n = 389) from 25 clinical sites (84% female, 68% Caucasian, 17% African descent, 8% Asian, 7% other). IgG anti-C1q against the collagen-like region was measured by ELISA. RESULTS: Prevalence of anti-C1q was 28% (86/308) in patients with SLE and 13% (49/389) in controls (OR = 2.7, 95% CI: 1.8-4, p < 0.001). Anti-C1q was associated with proteinuria (OR = 3.0, 95% CI: 1.7-5.1, p < 0.001), red cell casts (OR = 2.6, 95% CI: 1.2-5.4, p = 0.015), anti-dsDNA (OR = 3.4, 95% CI: 1.9-6.1, p < 0.001) and anti-Smith (OR = 2.8, 95% CI: 1.5-5.0, p = 0.01). Anti-C1q was independently associated with renal involvement after adjustment for demographics, ANA, anti-dsDNA and low complement (OR = 2.3, 95% CI: 1.3-4.2, p < 0.01). Simultaneously positive anti-C1q, anti-dsDNA and low complement was strongly associated with renal involvement (OR = 14.9, 95% CI: 5.8-38.4, p < 0.01). CONCLUSIONS: Anti-C1q was more common in patients with SLE and those of Asian race/ethnicity. We confirmed a significant association of anti-C1q with renal involvement, independent of demographics and other serologies. Anti-C1q in combination with anti-dsDNA and low complement was the strongest serological association with renal involvement. These data support the usefulness of anti-C1q in SLE, especially in lupus nephritis.

The French-Canadian validation of a disease-specific, patient-reported outcome measure for lupus.

OBJECTIVES: The objective of this paper is to perform the cross-cultural validation of the French version of the LupusPRO, a disease-targeted patient-reported outcome measure, among systemic lupus erythematosus (SLE) patients in Canada. METHODS: The French version of the LupusPRO and the MOS SF-36 were administered; demographic, clinical and serological characteristics were obtained. Disease activity (SELENA-SLEDAI and the Lupus Foundation of America definition of flare) and damage (SLICC/ACR SDI) were assessed. Physician disease activity and damage assessments were ascertained using visual analog scales. Internal consistency reliability (ICR), test-retest reliability (TRT), convergent and discriminant validity (against corresponding domains of the SF-36), criterion validity (against disease activity, damage or health status) and known group validity were tested. RESULTS: A total of 99 French-Canadian SLE patients participated (97% women, mean (SD) age 45.2 (14.5) years). The median (IQR) SELENA-SLEDAI and SDI were 3.5 (6.0) and 1.0 (2.0), respectively. The ICR of the LupusPRO domains ranged from 0.81 to 0.93 (except for lupus symptoms, procreation and coping), while TRT ranged from 0.72 to 0.95. Convergent and discriminant validity, criterion validity and known group validity against disease activity, damage and health status measures were observed. Confirmatory factor analysis showed a good fit. CONCLUSION: The LupusPRO has fair psychometric properties among French-Canadian patients with SLE.

Neurodevelopmental disorders in children born to mothers with systemic lupus erythematosus.

Children born to women with systemic lupus erythematosus seem to have a potentially increased risk of neurodevelopmental disorders compared to children born to healthy women. Recent experimental data suggest in utero exposure to maternal antibodies and cytokines as important risk factors for neurodevelopmental disorders. Interestingly, women with systemic lupus erythematosus display high levels of autoantibodies and cytokines, which have been shown, in animal models, to alter fetal brain development and induce behavioral anomalies in offspring. Furthermore, subjects with systemic lupus erythematosus and neurodevelopmental disorders share a common genetic predisposition, which could impair the fetal immune response to in utero immunologic insults. Moreover, systemic lupus erythematosus pregnancies are at increased risk of adverse obstetrical outcomes and medication exposures, which have been implicated as potential risk factors for neurodevelopmental disorders. In this article, we review the current state of knowledge on neurodevelopmental disorders and their potential determinants in systemic lupus erythematosus offspring.

Breast cancer in systemic lupus erythematosus.

OBJECTIVE: Evidence points to a decreased breast cancer risk in systemic lupus erythematosus (SLE). We analyzed data from a large multisite SLE cohort, linked to cancer registries. METHODS: Information on age, SLE duration, cancer date, and histology was available. We analyzed information on histological type and performed multivariate logistic regression analyses of histological types according to age, SLE duration, and calendar year. RESULTS: We studied 180 breast cancers in the SLE cohort. Of the 155 cases with histology information, 11 were referred to simply as 'carcinoma not otherwise specified'. In the remaining 144 breast cancers, the most common histological type was ductal carcinoma (n = 95; 66%) followed by lobular adenocarcinoma (n = 11; 8%), 15 cancers were of mixed histology, and the remaining ones were special types. In our regression analyses, the independent risk factors for lobular versus ductal carcinoma was age [odds ratio (OR) 1.07, 95% confidence interval (CI) 1.01-1.14] and for the 'special' subtypes it was age (OR 1.06, 95% CI 1.01-1.10) and SLE duration (OR 1.05, 95% CI 1.00-1.11). CONCLUSIONS: Generally, up to 80% of breast cancers are ductal carcinomas. Though our results are not definitive, in the breast cancers that occur in SLE, there may be a slight decrease in the ductal histological type. In our analyses, age and SLE duration were independent predictors of histological status.

Incidence and prevalence of adult systemic lupus erythematosus in a large US managed-care population.

OBJECTIVE: The objective of this paper is to determine the incidence and prevalence of adult systemic lupus erythematosus (SLE) in a large US managed-care population. METHODS: Subject inclusion in the incidence cohort required a medical claim with an SLE diagnosis and a service date from 2003 to 2008 that satisfied the following criteria: 1) ≥18 years on service date; 2) continuously enrolled for 24 months before and 12 months after service date; 3) in the 12 months after service date, ≥ one inpatient claim or ≥ two office or ER visits with an SLE diagnosis; 4) no SLE diagnosis 24 months prior to service date; and 5) no SLE medications 12 months prior to service date. Prevalence cohort subjects were identified using a similar algorithm and were not required to satisfy criteria 4) and 5). RESULTS: A total of 1,557 subjects were included in the incidence cohort, and 15,396 were included in the prevalence cohort. The overall age- and gender-adjusted SLE incidence rate (2003-2008) was 7.22 cases per 100,000 person-years. The annual prevalence of SLE (per 100,000 individuals) varied from 81.07 in 2003 to 102.94 in 2008. CONCLUSION: The SLE incidence in this large managed-care plan with geographic diversity was slightly higher than previous estimates, and the prevalence was within the range of previous estimates.

Decreased breast cancer risk in systemic lupus erythematosus: the search for a genetic basis continues.

PURPOSE: Recent work has demonstrated an important decrease in breast cancers for women with systemic lupus erythematosus (SLE). The reason behind this phenomenon is unknown. Our purpose was to explore whether the single nucleotide polymorphisms (SNPs) predisposing to SLE might be protective against breast cancer (in women in the general population). METHODS: We focused on loci relevant to 10 SNPs associated with SLE (with a p value of <10(-9)). We determined whether we could establish a decreased frequency of these SNPs in breast cancer cases versus controls, within the general population. To do this we used a large breast cancer genome-wide association study (GWAS) dataset, involving 3,659 breast cancer cases and 4,897 controls. These subjects were all primarily of European ancestry. RESULTS: The population-based GWAS breast cancer data we examined suggested little evidence for important associations between breast cancer and SLE-related SNPs. Within the general population GWAS data, a cytosine(C) nucleotide substitution at rs9888739 (on chromosome 16p11.2) showed a very weak inverse association with breast cancer. The odds ratio (OR) for the rs9888739-C allele was 0.907551 (p value 0.049899) in the GWAS breast cancer sample, compared to controls. There was a slightly stronger, positive, association with breast cancer for rs6445975-G (Guanine) on chromosome 3p14.3, with a breast cancer OR of 1.0911 (p value 0.0097). CONCLUSIONS: Within this large breast cancer dataset, we did not demonstrate important associations with 10 lupus-associated SNPs. If decreased breast cancer risk in SLE is influenced by genetic profiles, this may be due to complex interactions and/or epigenetic factors.

Demographic predictors of peanut, tree nut, fish, shellfish, and sesame allergy in Canada.

Background. Studies suggest that the rising prevalence of food allergy during recent decades may have stabilized. Although genetics undoubtedly contribute to the emergence of food allergy, it is likely that other factors play a crucial role in mediating such short-term changes. Objective. To identify potential demographic predictors of food allergies. Methods. We performed a cross-Canada, random telephone survey. Criteria for food allergy were self-report of convincing symptoms and/or physician diagnosis of allergy. Multivariate logistic regressions were used to assess potential determinants. Results. Of 10,596 households surveyed in 2008/2009, 3666 responded, representing 9667 individuals. Peanut, tree nut, and sesame allergy were more common in children (odds ratio (OR) 2.24 (95% CI, 1.40, 3.59), 1.73 (95% CI, 1.11, 2.68), and 5.63 (95% CI, 1.39, 22.87), resp.) while fish and shellfish allergy were less common in children (OR 0.17 (95% CI, 0.04, 0.72) and 0.29 (95% CI, 0.14, 0.61)). Tree nut and shellfish allergy were less common in males (OR 0.55 (95% CI, 0.36, 0.83) and 0.63 (95% CI, 0.43, 0.91)). Shellfish allergy was more common in urban settings (OR 1.55 (95% CI, 1.04, 2.31)). There was a trend for most food allergies to be more prevalent in the more educated (tree nut OR 1.90 (95% CI, 1.18, 3.04)) and less prevalent in immigrants (shellfish OR 0.49 (95% CI, 0.26, 0.95)), but wide CIs preclude definitive conclusions for most foods. Conclusions. Our results reveal that in addition to age and sex, place of residence, socioeconomic status, and birth place may influence the development of food allergy.

Features associated with cardiac abnormalities in systemic lupus erythematosus.

OBJECTIVES: To determine the prevalence of echocardiographic abnormalities and identify associated clinical and laboratory features in a large systemic lupus erythematosus (SLE) cohort. METHODS: Patients fulfilling ACR criteria for SLE underwent a transthoracic echocardiogram (TTE) between January 2005 and June 2006. Variables used as potential correlates included age, sex, ethnicity, lupus duration, lupus disease activity (SLEDAI), cumulative damage (SLICC/ACR damage index (DI)), arterial hypertension, diabetes, current smoking, medication use and laboratory data. Multivariate logistic regression was used to examine the association between TTE abnormalities and potential determinants. RESULTS: For the 217 subjects with a TTE performed during the study, the main abnormalities were of the mitral valve (37.3%) and included thickening (25.4%) and insufficiency (25.8%). Other findings included pulmonary artery pressure (PAP) ≥ 30( )mm( )Hg (10.1%), pericardial effusion (4.6%), hypokinesis (2.8%), and aortic insufficiency (3.7%). In multivariate analysis, mitral insufficiency was associated with the use of corticosteroids (OR 2.90; 95%CI 1.42-5.94) and hypokinesis with angiotensin-converting enzyme inhibitors (12.89; 1.06-157.18). Elevated PAP was associated with age (1.04; 1.01-1.07) and with DI (1.20; 1.01-1.42). CONCLUSION: Valvular abnormalities are frequent in patients with SLE, with mitral valve lesions occurring in over one third. TTE screening may be indicated in patients with SLE, especially for those with identified risk factors such as corticosteroid use.

Association of the Charlson comorbidity index with mortality in systemic lupus erythematosus.

OBJECTIVE: To investigate whether comorbidity as assessed by the Charlson Comorbidity Index (CCI) is associated with mortality in a long-term followup of systemic lupus erythematosus (SLE) patients. METHODS: Data were collected from 499 SLE patients attending the Lupus Clinic at the McGill University Health Center, Montreal, Quebec, Canada, and 170 SLE patients from the Department of Rheumatology at Lund University Hospital, Lund, Sweden. This included data on comorbidity, demographics, disease activity, the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI), and antiphospholipid antibody syndrome (APS). Variables were entered into a Cox proportional hazards survival model. RESULTS: Mortality risk in the Montreal cohort was associated with the CCI (hazard ratio [HR] 1.57 per unit increase in the CCI, 95% confidence interval [95% CI] 1.18-2.09) and age (HR 1.04 per year increase in age, 95% CI 1.00-1.09). The CCI and age at diagnosis were also associated with mortality in the Lund cohort (CCI: HR 1.35, 95% CI 1.13-1.60; age: HR 1.09, 95% CI 1.05-1.12). Furthermore, the SDI was associated with mortality in the Lund cohort (HR 1.40, 95% CI 1.19-1.64), while a wide CI for the estimate in the Montreal cohort prevented a definitive conclusion (HR 1.20, 95% CI 0.97-1.48). We did not find a strong association between mortality and sex, race/ethnicity, disease activity, or APS in either cohort. CONCLUSION: In this study, comorbidity as measured by the CCI was associated with decreased survival independent of age, lupus disease activity, and damage. This suggests that the CCI may be useful in capturing comorbidity for clinical research in SLE.

Acute lupus myocarditis: Clinical features and outcome.

BACKGROUND: Cardiomyopathy in systemic lupus erythematosus (SLE) may be secondary to myocardial inflammation (i.e. myocarditis) or to systemic complications such as hypertension. Symptomatic left ventricular dysfunction is the most common clinical presentation of cardiomyopathy and is potentially life threatening. Identifying the cause is critical as it dictates therapy. METHODS: We present three cases of left ventricular failure suggestive of myocarditis in SLE patients followed in the Lupus Clinic of the Montreal General Hospital over a 5-year period. RESULTS: The most frequent presentation is acute onset of a marked reduction of the left ventricular ejection fraction (LVEF). All patients were treated with cardiac support, prednisone, and additional immunosuppressive medications. Improvement of symptoms and LVEF was observed in two of three patients. CONCLUSION: Myocarditis is a rare, but life-threatening, manifestation of SLE. With immunosuppressive medications and cardiovascular support, the long-term outcome is usually favorable.

Breast, ovarian, and endometrial malignancies in systemic lupus erythematosus: a meta-analysis.

BACKGROUND: An increased lymphoma risk is well documented in systemic lupus (SLE). Less attention has been focused on women's cancers, even though SLE affects mostly females. Our objective was to estimate the risk of breast, ovarian, and endometrial cancers in SLE, relative to the general population. METHODS: Data were included from five recent studies of large SLE cohorts. The number of cancers observed was determined for each cancer type. The expected number of malignancies was ascertained from general population data. The parameter of interest was the standardised incidence ratio (SIR), the ratio of observed to expected malignancies. RESULTS: The five studies included 47,325 SLE patients (42,171 females) observed for 282,553 patient years. There were 376 breast cancers, 66 endometrial cancers, and 44 ovarian cancers. The total number of cancers observed was less than that expected, with SIRs of 0.76 (95% CI: 0.69, 0.85) for breast cancer, 0.71 (95% CI: 0.55, 0.91) for endometrial cancer, and 0.66 (95% CI: 0.49, 0.90) for ovarian cancer. CONCLUSIONS: Data strongly support a decreased risk of breast, ovarian, and endometrial cancers in SLE. This may be due to inherent differences in women in SLE (vs the general population) regarding endogenous oestrogen, other medications, and/or genetic make-up.

Prostate cancer in systemic lupus erythematosus.

Our research objective was to estimate prostate cancer risk in systemic lupus erythematosus (SLE), relative to the age-matched general population. A progressive literature review was performed to identify SLE cohort studies with cancer registry linkage for cancer ascertainment. Data were pooled from four studies of large SLE cohorts who met these criteria. The total number of prostate cancers observed was derived by pooling the incident cases across all studies. The total expected number of prostate, derived from applying appropriate general population cancer incidence data to the observed number of patient-years of follow-up for each study, was similarly determined. The parameter of interest was the standardized incidence ratio (SIR), the ratio of observed to expected malignancies. The four studies together provided a pool of 6,068 male SLE patients observed for a total of 38,186 patient-years (mean 6.3 years). Within these subjects, 80 prostate cancers were observed. In each contributing study, the number of cancers expected far exceeded that observed. The pooled SIR estimate for prostate cancer risk in males with SLE, compared to the general population, was 0.72 (95% CI 0.57, 0.89). These data suggest a decreased risk of prostate cancer in SLE; more definite conclusions require additional data. As alterations in androgen pathways can potentially alter prostate risk, a lower risk of prostate cancer in SLE could possibly be due to low hypoadrenergic states which some believe may occur in men with SLE; underlying genetic factors could also be at play. Further study of these issues in large cohorts is needed.

A targeted association study in systemic lupus erythematosus identifies multiple susceptibility alleles.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Multiple genetic and environmental factors contribute to the pathogenesis of this disease. Recent genome-wide association studies have added substantially to the number of genes associated with SLE. To replicate some of these susceptibility loci, single-nucleotide polymorphisms reported to be associated to SLE were evaluated in a cohort of 245 well-phenotyped Canadian SLE trios. Our results replicate previously reported associations to alleles of interferon regulatory factor 5 (IRF5), major histocompatibility complex (MHC), tumor necrosis factor (ligand) superfamily member 4 (TNFSF4), Kell blood group complex subunit-related family member 6 (XKR6), B-cell scaffold protein with ankyrin repeats 1 (BANK1), protein tyrosine phosphatase non-receptor type 22 (PTPN22), ubiquitin-conjugating enzyme E2L 3 (UBE2L3) and islet cell autoantigen 1 (ICA1). We also identify putative associations to cytotoxic T-lymphocyte-associated protein 4 (CTLA4), a gene associated with several autoimmune disorders, and ERBB3, a locus on 12q13 that was previously reported to be associated with type 1 diabetes. This study confirms the existence of multiple genetic risk factors for SLE, and supports the notion that some risk factors for SLE are shared with other inflammatory disorders.