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Background: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE)., Methods and Findings: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE. In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcgammaRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model., Conclusions: Fcgamma receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Objective: To determine if different categories of erythrocyte sedimentation rate (ESR) elevation are associated with disease activity and/or damage in systemic lupus erythematosus (SLE)., Methods: We studied 2317 study visits in 553 SLE patients (> or = 4 American College of Rheumatology criteria, < or = 5 years' disease duration at enrollment) from a multiethnic (Hispanic, African American, and Caucasian) longitudinal study of outcome. A study visit was done every 6 months for the first year and annually thereafter. Erythrocyte sedimentation rate (ESR) was measured using the Westergren method; results were expressed in 4 categories: < 25 (normal), 25-50 (mild elevation), 51-75 (moderate elevation), and > 75 (marked elevation) mm/h. Anti-dsDNA antibodies were measured at enrollment with the Crithidia luciliae assay. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM) and the Physician's Global Assessment (PGA). Because ESR is one of the measures evaluated in the SLAM, it was excluded from the total SLAM score. Disease damage was assessed with the Systemic Lupus International Collaborating Clinics damage index (SDI). The relationship between the SLAM (total and PGA) and SDI scores (at baseline and for all visits) and anti-dsDNA antibodies (at enrollment) with ESR was examined by univariable and generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered in all regression models., Results: The cohort consisted of 89.7% women with mean age 36.8 (SD 12.6) years and disease duration 4.6 (SD 3.2) years. GEE analyses showed that increasing levels of ESR and anti-dsDNA antibody positivity were independently associated with SLAM and PGA scores, at enrollment and for all visits. Overall, the associations of ESR with SLAM and PGA scores were stronger than for the presence of anti-dsDNA antibodies. At baseline, there was no relationship of ESR elevation or anti-dsDNA positivity with SDI scores. However, when all visits were studied, moderate and marked elevations of ESR were independently associated with SDI scores., Conclusion: Mild, moderate, and marked ESR elevations are strongly associated with disease activity in SLE. Moderate and marked ESR elevations are also associated with damage accrual. These associations are stronger than those for the presence of anti-dsDNA antibodies. Our data suggest that ESR could be used to assess disease activity and predict organ/system damage in a relatively rapid and inexpensive manner in SLE.

Objective: To determine how the American College of Rheumatology (ACR) criteria for the classification of systemic lupus erythematosus (SLE) accrue in a multiethnic cohort of SLE patients., Methods: SLE patients enrolled in a longitudinal study of outcome were analyzed (LUMINA; Lupus in Minorities: Nature versus nurture) for the manner in which ACR criteria manifestations occurred prior to the accrual of 4 of them. Time at which a criterion was said to be present was determined by review of all previously available medical records and interview. Univariable and multivariable Cox proportional hazard models were examined for the association with time to accrual of 4 ACR criteria; results were reported as hazard ratios., Results: There were 103 Texas Hispanic (of Mexican or Central America ancestry) patients, 55 Puerto Rico Hispanics, 176 African Americans, and 137 Caucasians. The mean +/- SD and median (range) time to accrual of 4 ACR criteria were 29.4 +/- 52.0 months and 9.1 (0-328.7) months; time was shortest for the Texas Hispanics (18.4 +/- 42.8 and 5.0 [0-248] months) and longest for the Caucasians (39.9 +/- 59.3 months and 17.7 [0-324.6] months). Arthritis was the most frequent first criterion (34.5%); it was followed by photosensitivity (18.8%). When 2 criteria occurred from the outset, the most frequent combination was arthritis and antinuclear antibody positivity followed by malar rash and photosensitivity. A Cox-regression multivariable model identified Hispanic ethnicity (from Texas) and HLA-DRB1*0301 as predictors of short time to criteria accrual, whereas older age and married/living together were associated with long time to criteria accrual., Conclusion: Significant variability in the evolution of ACR criteria manifestations does occur. Texas Hispanics are more likely to have a rapid evolution of criteria manifestations, but several years may elapse before ACR criteria are accrued.

Objectives: To compare the baseline clinical manifestations, immunological features, disease activity and damage accrual in systemic lupus erythematosus (SLE) patients from two US Hispanic subgroups., Methods: A total of 105 Hispanic SLE patients from Texas (a population of Mexican or Central American ancestry) and 81 from the island of Puerto Rico (all Puerto Ricans) participating in a longitudinal study of outcome were examined. The socio-economic/demographic, clinical and immunological variables were obtained at the time of enrollment (T(0)). Disease activity was determined with the Systemic Lupus Activity Measure (SLAM), and disease damage with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). Disease activity was also determined at the time of diagnosis (T(D))., Results: At T(0) Hispanics from Texas were younger than those from Puerto Rico (33.1 +/- 12.0 vs 37.5 +/- 11.6 yr, P = 0.0125). Both groups were similar with regard to gender distribution (92.4 vs 95.1% females) and disease duration (1.4 +/- 1.4 vs 1.7 +/- 1.3 yr). Hispanics from Texas were more likely to have serositis (60.0 vs 8.6%, P < 0.0001), renal involvement (41.0 vs 13.6%, P < 0.0001), psychosis (5.7 vs 0.0%, P = 0.0365) and thrombocytopenia (21.0 vs 3.7%, P = 0.0006). On the other hand, Hispanics from Puerto Rico were more likely to have photosensitivity (81.5 vs 41.0%, P < 0.0001), malar rash (65.4 vs 45.7%, P = 0.0074) and discoid rash (13.6 vs 2.9%, P = 0.0060). At baseline, the presence of anti-dsDNA antibodies was higher in Hispanics from Texas (69.5% vs 46.9%, P = 0.0018) while anti-Ro antibodies were more frequent in Hispanics from Puerto Rico (24.7 vs 11.4%, P = 0.0175). Mean SLAM scores at T(D) (12.9 +/- 6.4 vs 9.1 +/- 4.6, P < 0.0001) and T(0) (10.9 +/- 6.3 vs 6.6 +/- 3.8, P < 0.0001) were significantly higher in Hispanics from Texas. Similarly, mean SDI scores at T(0) were higher in Hispanics from Texas (0.67 +/- 1.08 vs 0.26 +/- 0.54, P = 0.0026). By stepwise Poisson regression, SDI scores were associated with older age, disease activity and ethnicity (Hispanics from Texas)., Conclusions: Early in SLE, marked differences are observed between Hispanics from Texas and Puerto Rico. Higher disease activity, more major organ involvement, higher frequency of anti-dsDNA antibodies and more damage accrual occur in Hispanic lupus patients from Texas than in those from Puerto Rico.

Objective: To determine the impact of wealth on disease activity in the multiethnic (Hispanic, African American, and Caucasian) LUMINA (Lupus in Minorities, Nature versus nurture) cohort of patients with systemic lupus erythematosus (SLE) and disease duration < or =5 years at enrollment., Methods: Variables (socioeconomic, demographic, clinical, immunologic, immunogenetic, behavioral, and psychological) were measured at enrollment and annually thereafter. Four questions from the Women's Health Initiative study were used to measure wealth. Disease activity was measured with the Systemic Lupus Activity Measure (SLAM). The relationship between the different variables and wealth was then examined. Next, the impact of wealth on disease activity was examined in regression models where the dependent variables were the SLAM score and SLAM global (physician). Variables previously found to impact disease activity plus the wealth questions were included in the models., Results: Questions on income, assets, and debt were found to distinguish patients into groups, wealthier and less wealthy. Less wealthy patients tended to be younger, women, noncaucasian, less educated, unmarried, less likely to have health insurance, and more likely to live below the poverty line. They also tended to have more active disease, more abnormal illness-related behaviors, less social support, and lower levels of self reported mental functioning. None of the wealth questions was retained in the regression models, although other socioeconomic features (such as African American ethnicity, poverty, and younger age) did., Conclusions: Wealth, per se, does not appear to have an additional predictive value, over and above traditional measures of socioeconomic status, in SLE disease activity.

Objective: To compare patient's and physician's assessment of disease activity in a multiethnic (Hispanic, African American, and Caucasian) cohort of systemic lupus erythematosus (SLE) patients., Methods: Three hundred patients with SLE from the LUMINA (Lupus in Minority populations: Nature versus nurture) cohort were included. Disease activity was assessed with the Systemic Lupus Activity Measure (SLAM); patients and physicians assessed disease activity using a 10-cm anchored visual analog scale (VAS). The difference between VAS scores was termed discrepancy (>1 cm was considered a priori clinically relevant). Selected sociodemographic, clinical, behavioral, and psychological variables were examined in relation to discrepancy in univariable and multivariable models adjusting for the physician global VAS score in order to eliminate ceiling and floor effects., Results: A discrepancy was exhibited by 58% of the patients. Abnormal laboratory findings were negatively associated with discrepancy, and poor self-perceived functioning and joint involvement were positively associated with discrepancy. Ethnicity did not account for discrepant perception of disease activity., Conclusion: Patients and physicians rate disease activity in SLE differently. Physicians appear to place more emphasis on laboratory features while patients place more emphasis on function.

Objective: To determine the features associated with mortality in a multiethnic US cohort of patients with systemic lupus erythematosus (SLE) within 5 years of study onset., Methods: Socioeconomic and demographic features (age, gender, ethnicity, marital status, education, occupation, poverty, and health-related behaviors [drinking, smoking, exercising]), clinical and immunologic features (disease duration, disease onset type, disease activity according to the Systemic Lupus Activity Measure [SLAM], disease damage according to the Systemic Lupus International Collaborating Clinics [SLICC] Damage Index [SDI], number of American College of Rheumatology criteria at diagnosis, organ system manifestations, fatigue and pain ratings, and medication usage and autoantibodies), immunogenetic features (HLA class II genotypes), and behavioral and psychosocial features (social support, illness-related behaviors, and helplessness), as obtained at enrollment into the study, were compared between survivors and deceased patients. Logistic regression analysis was used to determine significant independent risk factors for mortality., Results: Within 5 years of study onset, 34 of 288 patients have died. Fourteen deaths could be directly attributed to SLE and 11 to infections. In 1 patient the cause of death could not be determined. In the remaining 8 patients the cause of death was neither infectious nor disease-related. There were 10 deaths among Hispanics, 18 among African Americans, and 6 among Caucasians (P < 0.05). Variables associated with mortality in the univariable analyses included poverty, less than full-time employment, difficulty in accessing health care, shorter disease duration, cardiovascular and renal involvement, higher serum creatinine levels and lower hematocrit values, higher SLAM and SDI scores, lower use of antimalarial drugs, and higher use of (some) immunosuppressants. Specific autoantibodies and class II HLA genotypes were not associated with mortality. Poverty and higher baseline SLAM and SDI scores were independently associated with mortality in the multivariable analyses., Conclusions: Disease activity, disease damage, and poverty appear to be the most important determinants of mortality in this multiethnic US cohort of SLE patients. These results have applicability to the management of patients with SLE, a disease that more severely affects disadvantaged minority population groups.