Ethnicity in systemic lupus erythematosus (SLE): its influence on susceptibility and outcomes.

Ethnicity is a biological and a social construct which encompasses ancestral genes, cultural, geographic and socioeconomic characteristics shared within a population. It is clear that no homogeneous racial groups exist within the human race as demonstrated when examining ancestry informative markers. Both the genetic and non-genetic components of ethnicity exert influence in the expression and outcome of systemic lupus erythematosus (SLE), including disease activity, damage accrual, work disability and mortality. Although it is difficult to determine the extent to which the differences observed in these parameters are caused by genetic or non-genetic factors, early in the disease genetic factors seem to play a more important role as determinants of the differences observed between SLE patients from various ethnic groups. Over the course of the disease, non-genetic factors seem to play a more important role. By and large, SLE is more frequent and more severe with higher disease activity and more damage accrual in non-Caucasian populations (Hispanics, African descendants and Asians) than in Caucasians. To overcome these differences it is necessary to optimize health care access to disadvantaged populations and use innovative tools to increase disease awareness and improve treatment adherence.

Burden of autoantibodies and association with disease activity and damage in systemic lupus erythematosus.

OBJECTIVES: To determine whether immunological burden of autoantibodies as reflected by the number of cumulative antibodies present at inception and after 3 and 5 years is associated with or predicts subsequent disease activity and damage in lupus. METHODS: Patients with SLE followed from inception at a single centre between 1992 and 2007 were included. Twelve autoantibodies were assayed in each patient at years 1, 3 and 5 of disease. The relationship between the burden of autoantibodies and outcomes, SDI (Systemic Lupus International Collaborative Clinics Damage Index), AMS (Adjusted Mean SLEDAI-2K) and AMS excluding anti-ds DNA (AMS-DNA) was evaluated as an association and as prediction. We determined the association between autoantibody burden and outcomes at years 1, 3 and 5 and the prediction using autoantibody burden at year 1 and year 3 to predict outcomes at years 3 and 5 respectively. RESULTS: Between 1992 and 2007, 235 inception patients were identified. Of these, 223, 163 and 129 patients had 10 or more autoantibodies tested at years 1, 3 and year 5 following diagnosis respectively. There was no association between the burden at years 1, 3 and 5 and outcome measures at years 1, 3 and 5 respectively. Furthermore, burden of autoantibodies at years 1 and 3 did not predict the outcome measures at years 3 and 5 respectively. CONCLUSIONS: Immunological burden in SLE at years 1, 3 or 5 as reflected by the number of autoantibodies found, was not associated with or predictive of subsequent disease activity or damage over time.

Vitamin D insufficiency in a large female SLE cohort.

The objective of this study was to determine the vitamin D status and its relationship with disease and therapy features and with bone mineral density in women with systemic lupus erythematosus. Non-pregnant systemic lupus erythematosus women with dual-energy X-ray absorptiometry and vitamin D measurements performed between May 1 2005 and August 31 2006 were studied. In each patient, the lowest T-score of the first dual-energy X-ray absorptiometry scan during the study period was used. In postmenopausal women, a T-score > or = 1.0 standard deviation was considered normal, between -1.0 and -2.5 standard deviations osteopenia and < or = 2.5 standard deviations osteoporosis; in premenopausal women a T-score > or = 2.5 standard deviations was normal and < or = 2.5 standard deviations defined as reduced bone density. 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels were determined at the time of dual-energy X-ray absorptiometry. A 25-hydroxyvitamin D level of <80 nmol/L was defined as sub-optimal and a level <40 nmol/L as deficient. Demographic and clinical variables were investigated for association with vitamin D levels by univariate and multivariate analyses. One-hundred and twenty-four systemic lupus erythematosus women had dual-energy X-ray absorptiometry scans and vitamin D assays performed during the study period. Sub-optimal 25-hydroxyvitamin D levels were found in 82 (66.7%) and deficient 25-hydroxyvitamin D levels in 22 (17.9%) patients. The disease-related features examined at the time of vitamin D assays or bone mineral density showed no correlation with vitamin D levels by univariate analyses. Neither 25-hydroxyvitamin D nor 1,25-dihydroxyvitamin D was associated with bone mineral density status among these patients. A multivariate logistic regression model identified season, cumulative glucocorticoid exposure, and serum creatinine as being associated with 25-hydroxyvitamin D levels, whereas ethnicity, glucocorticoid exposure, and serum creatinine were associated with 1,25-dihydroxyvitamin D levels. In conclusion, sub-optimal vitamin D status is common in women with systemic lupus erythematosus and is related to season, cumulative glucocorticoid dose, and serum creatinine.

Familial aggregation of psoriatic arthritis.

OBJECTIVES: The aim of this study was to determine the recurrence risk of psoriatic arthritis (PsA) and uncomplicated psoriasis in first-degree relatives (FDRs) of patients with PsA. METHODS: All available FDRs (full siblings, parents and children) of 100 consecutive consenting patients attending a PsA clinic were evaluated for the presence of psoriasis and PsA using a standard protocol. The protocol included a screening questionnaire, physical examination by a rheumatologist, and radiographic and laboratory assessment. The prevalence of PsA and psoriasis in FDRs of the index cases was determined, and the recurrence risk ratio (lambda) was calculated, assuming a population prevalence of PsA of 0.25%, and a population prevalence of psoriasis of 2%. RESULTS: The 100 probands had 533 relatives. Eighty-four of them were deceased and 53 were unavailable (age <16 years). Of the remaining 396 FDRs, 107 did not participate (living too far away/did not consent). Thus, 289/396 (73%) of the available FDRs participated in the study. There were 130 siblings, 108 parents and 51 children. The prevalence of PsA and psoriasis among FDRs was 7.6% and 15.2%, respectively. The lambda(1 )was 30.4 for PsA and 7.6 for psoriasis. The prevalence of PsA and psoriasis in siblings was 7.7% and 17.7%, respectively. The lambda(S) was 30.8 for PsA and 8.8 for psoriasis. CONCLUSIONS: The recurrence risk ratio for both PsA and psoriasis is high in FDRs and siblings of patients with PsA. These results confirm that both PsA and psoriasis have a strong heritable component.

Systemic lupus erythematosus in a multiethnic cohort: LUMINA XXXV. Predictive factors of high disease activity over time.

AIM: To ascertain the predictive factors of high levels of disease activity in systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Patients with SLE (American College of Radiology criteria), aged >or=16 years, with disease duration 10). A basic multivariable model (including age, sex, ethnicity, health insurance, social support, abnormal illness-related behaviours, helplessness and prior disease activity) was first examined. Additional models were built by including other variables. RESULTS: 554 patients (100 Hispanics from Texas, 94 Hispanics from Puerto Rico, 199 African Americans, 161 Caucasians) and 2366 visits were analysed; 47% of the patients and 29% of the visits met the definition of high disease activity (more common among African Americans (72.0%) and Hispanics from Texas (71.3%) than among Caucasians (43.9%) and Hispanics from Puerto Rico (31.9%)). Variables found to predict high levels of disease activity were Hispanic (from Texas) and African American ethnicities, lack of health insurance, helplessness, abnormal illness-related behaviours and poor social support; age was negatively associated with high levels of disease activity. African admixture and anti-double-stranded DNA antibodies also predicted high levels of disease activity, as did prior disease activity. None of the human leucocyte antigen variables were retained in the models. CONCLUSIONS: Socioeconomic-demographic (age, ethnicity, health insurance), behavioural and psychological variables are important mediators of high levels of disease activity in SLE during its course. Interventions aimed at modifiable factors may improve the outcomes of SLE.

Systemic lupus erythematosus in a multiethnic US Cohort (LUMINA). XXX: association between C-reactive protein (CRP) gene polymorphisms and vascular events.

OBJECTIVES: To determine if a polymorphic GTn repeat in the intron of the C-reactive protein (CRP) gene associates with occurrence of vascular arterial events in systemic lupus erythematosus (SLE). METHODS: We performed a nested case-control study on the LUMINA cohort of 546 Hispanic, African-American and Caucasian SLE patients. Twenty-five patients who developed vascular arterial events (i.e. myocardial infarction, angina, coronary artery bypass graft surgery, stroke, claudication, gangrene or significant tissue loss and/or arterial peripheral thrombosis) after enrolment were selected as cases and 32 ethnically matched patients with no previous vascular arterial events served as controls. Their CRP gene GTn polymorphism and plasma CRP was determined. RESULTS: Patients with vascular events had more severe SLE and were more likely to have plasma CRP in the highest quintile of measured values. The overall distribution of GTn alleles for patients with vascular events had a greater number of the GT20 variant compared with controls [26.0% of alleles (13/50) vs 15.6% (10/64)]. This greater number of GT20 in patients with vascular events was observed for African-Americans [29.2% (7/24) vs 21.0% (8/38)] and Hispanics [33.0% (4/12) vs 0% (0/16)] but not for Caucasians [14.3% (2/14) vs 20.0% (2/10)]. For African-Americans and Hispanics combined (45 patients), the frequency of GT20 in those with vascular events (30.6%, 11/36) was significantly higher than in those without them (14.8%, 8/54) (P<0.05, one-tailed test for difference in proportions). When patients were categorized according to the number of GT20 alleles they carried (thus GT20/GT20, GT20/GTx or GTx/GTx, where x is any allele other than GT20), for both African-Americans and Hispanics the likelihood of vascular arterial events increased in proportion with the GT20 dose, and all GT20-homozygous patients developed vascular arterial events. CONCLUSIONS: The CRP GT20 variant is more likely to occur in African-American and Hispanic SLE patients than in Caucasian ones, and SLE patients carrying the GT20 allele are more likely to develop vascular arterial events.