Effects of statins on proinflammatory/prothrombotic biomarkers and on disease activity scores in SLE patients: data from LUMINA (LXXVI), a multi-ethnic US cohort.

OBJECTIVES: We sought to determine the effect of statin therapy on the levels of proinflammatory/prothrombotic markers and disease activity scores in patients with SLE in a multi-ethnic, multi-centre cohort (LUMINA). METHODS: Plasma/serum samples from SLE patients placed on statins (n=21) therapy taken before and after at least 6 months of treatment were tested. Disease activity was assessed using SLAM-R scores. Interleukin (IL)-1ß, IL-6, IL-8, tumour necrosis factor (TNF)-α, vascular endothelial growth factor (VEGF) and soluble CD40 ligand (sCD40L) levels were determined by a multiplex immunoassay. Soluble intercellular cell adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1 and anticardiolipin (aCL) antibodies were evaluated using ELISA assays while high sensitivity C-reactive protein (hsCRP) was assessed by nephelometry. Plasma/serum samples from frequency- matched healthy donors were used as controls. RESULTS: Levels of IL-6, VEGF, sCD40L and TNF-α were significantly elevated in SLE patients versus controls. Statin therapy resulted in a significant decrease in SLAM-R scores (p=0.0199) but no significant changes in biomarker levels were observed. There was no significant association of biomarkers with SLAM-R scores. CONCLUSIONS: Statin therapy resulted in significant clinical improvement in SLE patients, underscoring the use of statins in the treatment of SLE.

Systemic lupus erythaematosus in a multiethnic US cohort (LUMINA) LIII: disease expression and outcome in acute onset lupus.

OBJECTIVE: To determine the features associated with acute onset systemic lupus erythaematosus (SLE). METHODS: A total of 631 SLE patients from LUMINA (for "lupus in minority populations: nature vs nurture"), a multiethnic (Hispanics, African-Americans and Caucasians) cohort, were studied. Acute disease onset was defined as the accrual of > or = 4 American College of Rheumatology (ACR) criteria for the classification of SLE in < or = 4 weeks. Socioeconomic demographic features, clinical manifestations, disease activity, damage accrual, mortality, autoantibodies, HLA class II and FCGR alleles, behavioural/psychological variables were compared between patients with acute and insidious disease onset by univariable (chi(2) and Student t test) and multivariable (stepwise logistic regression) analyses. RESULTS: A total of 94 (15%) patients had acute disease onset. In the multivariable analysis, patients with acute onset lupus had more renal involvement (odds ratio (OR) = 1.845, 95% CI 1.076-3.162; p = 0.026) and higher disease activity (OR = 1.057, 95% CI 1.005-1.112; p = 0.030). By contrast, age (OR = 0.976, 95% CI 0.956-0.997; p = 0.025), education (OR = 0.901, 95% CI 0.827-0.983, p = 0.019), health insurance (OR = 0.423, 95% CI 0.249-0.718; p = 0.001) and skin involvement (OR = 0.346, 95% CI 0.142-0.843; p = 0.019) were negatively associated with acute onset lupus. No differences were found regarding the serological, genetic and behavioural/psychological features; this was also the case for damage accrual and mortality. CONCLUSIONS: Patients with acute onset lupus seem to be younger, have a lower socio-economic status and display more severe disease in terms of clinical manifestations and disease activity. However, intermediate (damage) and long-term (mortality) outcomes appear not to be influenced by the type of disease onset in SLE.

Systemic lupus erythematosus in a multiethnic US Cohort LUMINA XLVIII: factors predictive of pulmonary damage.

The objective of this study was to determine the factors predictive of time to the occurrence of pulmonary damage in systemic lupus erythematosus (SLE). Six-hundred and twenty-six SLE patients from a multiethnic (Hispanics, African Americans and Caucasians) longitudinal study of outcome were studied. Pulmonary damage was defined as per the Systemic Lupus International Collaborating Clinics Damage Index. Socioeconomic-demographic, clinical, genetic, serological features, pharmacologic treatments, behavioural, psychological and disease activity [as per the Systemic Lupus Activity Measure-Revised (SLAM-R)] were examined. Factors associated with time to the occurrence of pulmonary damage were examined by Cox proportional hazards regressions. A Kaplan-Meier survival curve was also examined. Forty-six (7.3%) patients had pulmonary damage after a mean (SD) total disease duration of 5.3 (3.6) years. Among those patients, 25 had pulmonary fibrosis, 12 pulmonary hypertension, eight pleural fibrosis, four pulmonary infarction and four shrinking lung syndrome. Seven patients had more than one type of lung damage. Cumulative rates of pulmonary damage at five and 10 years were 7.6% and 11.6%, respectively. In the multivariable analyses, age (HR = 1.033, 95% CI 1.006-1.060; P = 0.0170), pneumonitis (HR = 2.307, 95% CI 1.123-4.739; P = 0.0229) and anti-RNP antibodies (HR = 2.344, 95% CI 1.190-4.618; P = 0.0138) were associated with a shorter time to the occurrence of pulmonary damage while photosensitivity (HR = 0.388, 95% CI 0.184-0.818; P = 0.0128) and oral ulcers (HR = 0.466, 95% CI 0.230-0.942; P = 0.0335) with a longer time. Pulmonary damage is relatively common in SLE. Age, pneumonitis and anti-RNP antibodies were associated with a shorter time to the development of permanent lung disease.

Predictors of post-partum damage accrual in systemic lupus erythematosus: data from LUMINA, a multiethnic US cohort (XXXVIII).

OBJECTIVE: To determine the impact of pregnancy on systemic lupus erythematosus (SLE) outcome. METHODS: SLE patients, age >or=16 yrs, disease duration

Early clinical manifestations, disease activity and damage of systemic lupus erythematosus among two distinct US Hispanic subpopulations.

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.

Frequency of HLA-DQB*06 in Caucasian,African American, and Mexican American patients with a positive direct antiglobulin test.

A reduced frequency of HLA-DQ6 in patients with a positive direct antiglobulin test (DAT) was previously reported but race was undisclosed. Therefore, we investigated a total of 275 patients (80 Caucasian, 113 African American, and 82 Mexican American) and 518 normal controls (205 Caucasian, 208 African American, and 105 Mexican American). These were typed for class II HLA antigens using molecular techniques. A DAT was performed on each patient's red cells drawn into EDTA using both mouse and rabbit polyspecific reagents. Of 275 patients tested, 73 (27%) had a positive DAT (12 Caucasians, 35 African Americans, and 26 Mexican Americans). We found that 5 (42%) Caucasian patients and 103 (50%) Caucasian controls possessed the DQB*06 allele (p =.56). In the African American group, 15 (43%) patients and 91 controls (44%) were DQB*06 positive (p =.92). Six Mexican American patients (23%) and 21 controls (20%) had the DQB*06 allele (p =.72). This article underscores the need to use race-matched controls when genetic disease associations are sought.

Interrelationship of major histocompatibility complex class II alleles and autoantibodies in four ethnic groups with various forms of myositis.

OBJECTIVE: To examine interrelationships among myositis subsets, autoantibodies, and major histocompatibility complex (MHC) class II alleles across ethnic lines, and to localize genetic susceptibility (presence of HLA-DR versus DQ) to myositis within the MHC class II region. METHODS: MHC class II alleles (HLA-DRB1, DQA1, and DQB1, detected by DNA oligotyping) and myositis-specific autoantibodies (MSA) were determined in 224 patients with various myositis syndromes, including 89 whites, 89 African-Americans, 25 Mexican-Americans, and 21 Japanese. RESULTS: Anti-Jo-1 (histidyl-transfer RNA [tRNA] synthetase) and other MSAs (anti-PL-12, anti-PL-7, anti-OJ, anti-EJ, anti-KJ, anti-tRNA, and anti-signal recognition particle) were equally distributed among the races, but occurred more often in patients with polymyositis (PM) than in those with dermatomyositis (DM) or other myositis syndromes. MSA frequencies were significantly positively associated with anti-Ro (SS-A) (P = 0.002), and significantly negatively associated with anti-U1 RNP (P = 0.003). Frequencies of the HLA-DRB1*0301 (DR3), DQA1*0501, and DQB1*0201 (DQ2) alleles (and haplotype) were each increased in white patients with myositis, especially those with PM, but most strikingly in those with MSAs. However, in the other ethnic groups, except the Japanese group, only frequencies of HLA-DQA1*0501 and the structurally similar DQA1*0401 alleles were significantly increased. The presence of HLA-DQA1*0501 or *0401 was most significantly associated with anti-Jo-1, anti-PL-12, and other MSAs, compared with myositis patients without MSAs (P = 0.0008, Pcorr = 0.01, odds ratio [OR] = 3.7), and with normal, ethnically matched controls (P = 3 x 10(-7), Pcorr = 1 x 10(-6), OR = 6.5). Among MSA-positive patients who were negative for HLA-DQA1*0501 and *0401, including Japanese patients, the HLA-DQA1*0102 and *0103 alleles predominated. In addition, there appeared to be a negative association of the HLA-DR2 alleles (DRB1*1501 and *1503) with PM (P = 0.007, Pcorr not significant, OR = 0.39), but not with DM or myositis overall. CONCLUSION: By transracial gene mapping, genetic susceptibility to anti-Jo-1 and other MSAs in patients with myositis can be localized within the MHC region to the HLA-DQA1 locus.

Major histocompatibility complex class II and C4 alleles in Mexican Americans with systemic lupus erythematosus.

Few data exist on associations of class II and class III alleles of the major histocompatibility complex (MHC) and susceptibility to systemic lupus erythematosus (SLE) in Mexican Americans, a group of predominantly mixed Spanish and Native American ancestry. Therefore, MHC class II alleles (HLA-DRB1, DQA1, DQB1, DPA1 and DPB1 alleles) and C4 allotypes were determined in 52 Mexican American SLE patients and 105 ethnic-matched controls. HLA-DRB1*0301 and C4A*Q0 were each increased in the SLE patients, especially HLA-DRB1*0301 in those with anti-Ro/SSA autoantibodies. C4A*Q0 was associated with HLA-DRB1*0301 only in a minority of patients and controls. Anti-U1RNP antibodies were significantly associated with the presence of HLA-DQB1*0302, and the risk for the production of anti-Ro antibodies was heightened by the presence of at least three (out of four possible) DQA1 chains possessing a glutamine at position 34 and/or DQB1 chains a leucine at position 26 of their outermost domains. Thus the HLA class II and C4 null allele associations that have been noted in other ethnic groups are also found in Mexican Americans, suggesting shared susceptibility factors across ethnic lines in predisposition to SLE.