RESUMO
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.
Assuntos
Nefropatias/etiologia , Nefropatias/genética , Falência Renal Crônica/etiologia , Falência Renal Crônica/genética , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/genética , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Predisposição Genética para Doença , Genótipo , Antígenos HLA/genética , Humanos , Nefropatias/epidemiologia , Falência Renal Crônica/epidemiologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/etnologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Porto Rico/etnologia , Receptores de IgG/genética , Texas/etnologia , Fatores de TempoRESUMO
OBJECTIVE: To determine if lymphopenia is associated with clinical/immunologic manifestations, disease activity, and disease damage in systemic lupus erythematosus (SLE). METHODS: The study group comprised 591 patients with SLE participating in a multiethnic, longitudinal outcome study. Cumulative clinical/immunologic (per American College of Rheumatology criteria) and pharmacologic treatment variables were obtained at enrollment (T0) and last visit (TL). Lymphopenia (<1,500/mm3) was scored only when clinically attributable to SLE and not to medications or other causes. Lymphocyte counts were expressed in 4 categories per the Systemic Lupus Activity Measure (SLAM): normal (> or =1,500/mm3), mild (1,000-1,499/mm3), moderate (500-999/mm3), and marked (<500/mm3). Disease activity was assessed with the SLAM and the Physician's Global Assessment (PGA). Disease damage was determined with the Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI). The relationship of lymphopenia with cumulative clinical/immunologic and pharmacologic treatment variables was first examined, then the association between the SLAM, PGA, and SLICC-DI scores with different categories of lymphopenia was examined by generalized estimating equation (GEE) regression analyses. Ethnicity, age, and sex were entered into all regression models. RESULTS: At T0 and TL, lymphopenia was found to be positively associated with renal involvement, leukopenia, anti-double-stranded DNA antibodies, anti-Ro antibodies, and the use of glucocorticoids, azathioprine, and methotrexate, but was negatively associated with photosensitivity. On GEE analyses, marked lymphopenia at T0 and moderate and marked lymphopenia for all visits were independently associated with higher SLAM, PGA, and SLICC-DI scores. CONCLUSION: Lymphopenia is associated with several clinical/immunologic manifestations in SLE. Moderate and marked lymphopenia are associated with higher disease activity and damage accrual.
Assuntos
Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/etnologia , Linfopenia/complicações , Linfopenia/etnologia , Adulto , Anticorpos Antinucleares/imunologia , Estudos de Coortes , DNA/imunologia , Progressão da Doença , Feminino , Humanos , Nefropatias/etiologia , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/fisiopatologia , Linfócitos/patologia , Linfopenia/sangue , Linfopenia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Índice de Gravidade de Doença , Estados Unidos/etnologiaRESUMO
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.
Assuntos
Sedimentação Sanguínea , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/patologia , Índice de Gravidade de Doença , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Alabama/epidemiologia , Estudos de Coortes , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Estudos Longitudinais , Lúpus Eritematoso Sistêmico/sangue , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Psicologia , Porto Rico/epidemiologia , Texas/epidemiologia , População Branca/estatística & dados numéricosRESUMO
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.