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Biomedical subjects

J D Reveille

Publications and source records attributed to J D Reveille.

At least 37 records · Page 2Linked to original sources
PubMed2003

Clinical, immunogenetic and outcome features of Hispanic systemic lupus erythematosus patients of different ethnic ancestry.

The aim of this study was to compare and contrast the clinical, immunogenetic and outcome features of two subgroups of Hispanic patients with systemic lupus erythematosus (SLE), one from Northern Spain (Spaniards) and one of from the USA (Hispano-Americans: Hispanics primarily of Mexican ancestry (Amerindian and Spaniard backgrounds). Patients with SLE as per the American College of Rheumatology classification criteria, from two University-affiliated Hospitals (Universidad de Cantabria) and disease of five or less years in duration (n = 28) and with four years of follow up constituted the Spaniard subgroup. Fifty-two patients of Hispano-American ancestry from the LUMINA (Lupus in Minority populations: Nature versus Nurture) cohort constituted the Hispano-American subgroup. Patients were studied using a similar protocol. In short, sociodemographic, clinical, immunological, immunogenetic and psychosocial and behavioral features were obtained at enrollment into the study (baseline visit) and yearly thereafter. The relationship between these variables and disease activity at baseline and over time, as measured by the systemic lupus activity measure (SLAM) and disease damage, as measured by the SLICC (Systemic Lupus International Collaborating Clinics) Damage Index (SDI) were determined. Variables found to be significant at P = 0.10 were then entered into multivariable linear regression models with disease activity at baseline and over time, and damage as the outcome measures. Patients of Hispano-American and Spaniard ethnicity had comparable sociodemographic features except for home density, which was higher among the Hispano-Americans. HLA-DRB1*08 was associated with SLE among the Hispano-Americans but not among the Spaniards. Hispano-American patients had more severe disease as manifested by more frequent clinical manifestations (renal and neurological), higher SLAM scores at baseline and over time and higher SDI scores at the year 4 visit (that despite the fact that Hispano-American patients had overall shorter disease duration than the Spaniard patients). Hispano-American ethnicity, younger age at disease onset and the number of ACR criteria at baseline and over time were consistently associated with disease activity, whereas increased home density and the absence of HLA-DRB1*0301 were significant predictors only over time. Disease damage was associated with disease activity over time, the number of ACR criteria at baseline, increased home density and the presence of HLA-DRB1*08. This is the first longitudinal study of SLE in two different Hispanic subgroups. Hispanics with a strong Amerindian background have a more serious disease than that observed in Spaniards. Genetic and socio-economic differences between these two Hispanic subgroups probably account for these findings.

Adult↗
PubMed2002

Baseline characteristics of a multiethnic lupus cohort: PROFILE.

PURPOSE: To report the baseline characteristics of a US multi-ethnic, multi-regional, multi-institution cohort of patients with systemic lupus erythematosus (SLE) and how it was constituted. METHODS: Patients with SLE per American college of Rheumatology (ACR) classification criteria, 16 years of age and older, with disease of 10 years or less, of Hispanic (H), African American (AA) or Caucasian (C) ethnicity and living in the geographic catchment areas of the participating institutions (the University of Alabama at Birmingham (UAB), Johns Hopkins University (JHU), The University of Texas-Houston Health Science Center (UTH) were eligible to enter the combined cohort (PROFILE, herein). Data from the individual SLE cohorts were pooled and the PROFILE cohort characteristics examined using descriptive statistics. Variables predictive of renal damage were then examined by logistic regression. RESULTS: The PROFILE cohort constituted by 568 patients (H = 78, AA = 216, C = 260 (13 other ethnicities)) is predominantly female. Non-C had a greater number of ACR criteria, and of renal involvement. Among the two non-C groups, a higher proportion of H patients have developed overall renal damage, as well as decreased glomerular filtration rate. Other than Hispanic ethnicity (odds ratio, OR = 6.27, confidence limits, CL = 1.96-220.01), sustained hypertension (OR = 14.16, CL = 4.42-44.33) [corrected] was a significant predictor of renal damage, whereas belonging to the JHU cohort was protective (OR = 0.18, CL = 0.05-0.63). CONCLUSIONS: We have constituted a large US multi-ethnic SLE cohort. Renal involvement was found to be more frequent among the non-C; within them, the H patients seem to be at higher risk for the occurrence of renal damage.

Adolescent↗
PubMed2002

Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis.

The purpose of this study was to determine the cumulative incidence of lupus nephritis (LN) and the factors predictive of its occurrence in a multiethnic systemic lupus erythematosus (SLE) cohort. We studied 353 SLE patients as defined by the American College of Rheumatology (ACR) criteria (65 Hispanics, 93 African-Americans and 91 Caucasians). First, we determined the cumulative incidence of LN in all patients. Next, we determined the predictors for LN in those with nephritis occurring after diagnosis. The dependent variable, LN, was defined by: (1) A renal biopsy demonstrating World Health Organization (WHO), class II-V histopathology; and/or (2) proteinuria > or = 0.5 g/24 h or 3+ proteinuria attributable to SLE; and/or (3) one of the following features also attributable to SLE and present on two or more visits, which were performed at least 6 months apart--proteinuria > or = 2+, serum creatinine > or = 1.4 mg/dl, creatinine clearance < or = 79 ml/min, > or = 10 RBCs or WBCs per high power field (hpf), or > or = 3 granular or cellular casts per hpf. Independent variables assessed at diagnosis, and if absent, at baseline, were from four domains: sociodemographic, clinical, immunologic and immunogenetic (including the complete antibody profile and MHC class II alleles), and health habits. Variables with P < 0.05 by chi square analyses were entered into domain-specific stepwise logistic regression analyses controlling for disease duration, with LN as the dependent variable. Significant domain-specific regression variables (P < or = 0.1) were then entered into an overall model. The cumulative incidence of LN was 54.3% in all patients, and 35.3% for those developing LN after diagnosis. LN after diagnosis occurred in 43.1% of 65 Hispanics, 50.5% of 93 African-Americans, and 14.3% of 91 Caucasians, P < 0.0001. The duration of follow-up for those with LN after diagnosis was 5.5+/-2.4 vs 4.0+/-2.9 years for those without LN. Hispanic (odds ratio (OR) = 2.71, 95% confidence limits (CL) = 1.07-6.87, P < 0.04) and African-American ethnicities (OR = 3.13, 95% CL = 1.21-8.09, P < 0.02), not married or living together (OR = 3.45, 95% CL = 1.69-7.69, P < 0.0003), higher SLAM score (OR = 1.11, 95% CL = 1.02-1.19, P < 0.007), anti-dsDNA (OR = 3.14, 95% CL = 1.50-6.57, P < 0.0001) and anti-RNP (OR = 4.24, CL = 1.98-9.07, P < 0.0001) antibodies were shown to be significant predictors of the occurrence of LN. Repeated analyses excluding the patients with missing HLA data showed that absence of HLA-DQB1*0201 was also a significant predictor for the occurrence of LN (OR = 2.34, CL = 1.13-5.26, P < 0.04). In conclusion, LN occurred significantly more often in Hispanics and African-Americans with SLE. Sociodemographic, clinical and immunologic/immunogenetic factors seem to be predictive of LN occurring after the diagnosis of SLE has been made.

Black or African American↗
PubMed2001

Systemic sclerosis (scleroderma): specific autoantigen genes are selectively overexpressed in scleroderma fibroblasts.

The pathogenesis of systemic sclerosis (SSc) involves complex interactions between activated fibroblasts eventually leading to fibrosis, and impaired immune tolerance characterized by a variety of circulating SSc-specific autoantibodies. The expression of autoantigens in fibroblasts, a key target tissue in SSc, may play an important role in this process. To obtain a global view of this process, we examined gene expression profiles of SSc dermal fibroblasts using cDNA microarrays. The results show that dermal fibroblasts from SSc patients obtained from either affected or unaffected skin displayed a characteristic pattern of increased SSc autoantigen gene expression compared with that from normal controls. In particular, fibrillarin (p = 0.028), centromeric protein B (p = 0.01), centromeric autoantigen P27 (p = 0.042), and RNA polymerase II (220 kDa; p = 0.02) were significantly overexpressed in SSc fibroblasts. Quantitative RT-PCR confirmed overexpression of these autoantigens and also revealed increased levels of DNA topoisomerase I transcripts in SSc fibroblasts compared with normal control fibroblasts (p = 0.0318). The polymyositis/scleroderma autoantigen gene was overexpressed in some SSc patients (p = 0.09). To examine the specificity of these overexpressed autoantigen genes for SSc and its tissue specificity for fibroblasts, cDNA microarrays of dermal fibroblasts from patients with eosinophilic fasciitis and scleromyxedema were studied as well as PBMC and muscle biopsies from SSc patients. None of these tissues showed significant alterations in gene expression of SSc-specific autoantigens. Therefore, SSc-associated autoantigen genes are selectively overexpressed in SSc dermal fibroblasts, a major tissue involved in disease pathogenesis.

Autoantigens↗
PubMed2001

Low-binding alleles of Fcgamma receptor types IIA and IIIA are inherited independently and are associated with systemic lupus erythematosus in Hispanic patients.

OBJECTIVE: To examine the relationship between allelic polymorphisms of IgG receptors (FcgammaR) and the development of lupus nephritis in a prospective study, and to determine the distribution of FcgammaR haplotypes (FcgammaRIIA and FcgammaRIIIA genotypes) in lupus patients and disease-free control subjects. METHODS: We studied 67 Hispanic systemic lupus erythematosus (SLE) patients from a prospective study of outcome and 53 disease-free control subjects. Patients were followed up longitudinally for 3 years. FcgammaRIIA and FcgammaRIIIA genotypes were determined using allele-specific polymerase chain reaction. RESULTS: Nephritis was present in 28% of patients at entry into the study and in 69% at the end of 3 years. In the nephritis group (n = 46), as well as the entire SLE cohort, there was a predominance of genotypes with low-binding alleles (FcgammaRIIa-R131 and FcgammaRIIIa-F176) at both loci (SLE nephritis patients 89% versus controls 62%; P < 0.002; odds ratio 0.20 [95% confidence interval 0.05-0.6] for risk of nephritis in individuals homozygous for either FcgammaRIIa-H131 or FcgammaRIIIaV176). The frequency of individuals homozygous for high-binding alleles at either locus decreased as the burden of disease increased (P < 0.002, by Mann-Whitney test). There was no linkage disequilibrium between FcgammaRIIA and FcgammaRIIIA in Hispanics, yet in the SLE patients, there was a clear overrepresentation of the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype (SLE patients 48% versus controls 30%) and a decrease in the frequency of the high-binding haplotype (4% versus 23%) (P < 0.002). CONCLUSION: We observed an increase in the frequency of low-binding FcgammaR alleles in an SLE population with a high prevalence of renal disease. The apparent selection for the FcgammaRIIa-R131;FcgammaRIIIa-F176 haplotype in Hispanic patients suggests that low-binding alleles of both FcgammaRIIa and FcgammaRIIIa confer risk for SLE and may act additively in the pathogenesis of disease, whereas the high-binding haplotype FcgammaRIIa-H131;FcgammaRIIIa-V176 is protective, particularly in the homozygous state.

Alleles↗
PubMed2001

Systemic lupus erythematosus in three ethnic groups. VII [correction of VIII]. Predictors of early mortality in the LUMINA cohort. LUMINA Study Group.

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.

Black or African American↗
PubMed2001

Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts.

OBJECTIVE: To determine the frequency with which scleroderma (systemic sclerosis; SSc) recurs in families and the familial relative risk (lambda) in the US. METHODS: Family histories of SSc were prospectively surveyed in 3 large US cohorts of SSc patients, 2 in Texas and 1 in Michigan. Diagnoses of familial SSc were verified by rheumatologist evaluation and/or review of medical records. Familial relative risks for first-degree relatives (lambda1) and siblings (lambdas) were calculated using actual reported counts of first-degree relatives in 2 cohorts and recent estimates of SSc prevalence in the US. RESULTS: Compared with the estimated prevalence of SSc in the US (2.6 cases/10,000 population [0.026%]), the disease occurred in 1 or more first-degree relatives in 1.5-1.7% of SSc families in the 3 cohorts (or 11 of 703 families [1.6%]), a significant increase. Familial relative risks in first-degree relatives in the 3 cohorts ranged from 10 to 16 (13 combined), and in siblings they ranged from 10 to 27 (15 combined). CONCLUSION: SSc occurs significantly more frequently in families with scleroderma (1.6%) than in the general population (0.026%). A positive family history of SSc is the strongest risk factor yet identified for SSc; however, the absolute risk for each family member remains quite low (<1%).

Black People↗
PubMed2001

Systemic lupus erythematosus in three ethnic groups. IX. Differences in damage accrual.

OBJECTIVE: To determine the factors predictive of damage in a multiethnic (Hispanic, African American, and Caucasian) LUMINA (lupus in minority populations, nature versus nurture) cohort of patients with systemic lupus erythematosus (SLE) with disease duration of < or =5 years at enrollment (T0). METHODS: Variables (socioeconomic/demographic, clinical, immunologic, immunogenetic, behavioral, and psychological) were measured at T0 and annually thereafter. Disease damage was measured with the Systemic Lupus International Collaborating Clinics Damage Index (SDI), and disease activity was measured with the Systemic Lupus Activity Measure. The relationship between the different variables and the SDI at the last visit (TL) was examined (mean followup from diagnosis to TL 61 months; adjusted for disease duration). Poisson regression was used to identify the independent association between the different variables and SDI scores at TL. RESULTS: Seventy-two Hispanics, 104 African Americans, and 82 Caucasians were included. One-half of patients had not accrued any damage. Caucasians had the lowest SDI scores at T0, and Hispanics had the highest scores at TL. Renal damage occurred more frequently among Hispanics and African Americans, while integument damage was more frequent among African Americans. Neuropsychiatric (20%), renal (16%), and ocular (15%) damage occurred most frequently among all patients. Independent predictors of SDI at TL were age, corticosteroid use (maximum dose at T0), number of American College of Rheumatology (ACR) criteria met, disease activity, and abnormal illness-related behaviors. Other variables were less consistently associated with damage accrual (poverty in African Americans, lack of HLA-DRB1*0301 in Hispanics, presence of HLA-DQB1*0201 and acute onset of SLE in Caucasians). CONCLUSION: Damage in SLE occurs from the outset in some, but not all, patients; Hispanics accrue damage more rapidly. Disease factors (corticosteroid use, number of ACR criteria met, disease activity, and acute-onset type) are important, but age and abnormal illness-related behaviors also contribute to overall damage in SLE.

Adult↗
PubMed2001

Glutathione S-transferase genotypes in systemic sclerosis and their association with clinical manifestations in early disease.

The glutathione S-transferases (GSTs) are a family of enzymes involved in limiting oxidative damage to tissues. Null alleles for one or more of the GST enzymes, especially GSTM1, reportedly occur more frequently in patients with Sjögren's syndrome and systemic lupus erythematosus who possess certain autoantibodies. Because systemic sclerosis (SSc) is a disease in which oxidative damage has been hypothesized to contribute both to immune dysfunction and tissue damage, we sought to determine if patients from a multi-ethnic cohort of SSc patients with early disease (< or =5 years) were more likely than ethnically-matched normal controls to have null alleles for GSTM1 (M1) and/or GSTT1 (T1), and if the null allele status correlated with any major disease features. The data show that while M1 and T1 null genotypes were not significantly increased in SSc compared to ethnically matched controls, their frequencies (especially T1 nulls) were significantly higher among SSc patients with hypertension and pulmonary involvement. This suggests that GST genotype may be a genetic factor that contributes to clinical disease expression in SSc.

Genotype↗
PubMed2001

Lack of association of a functionally relevant single nucleotide polymorphism of matrix metalloproteinase-1 promoter with systemic sclerosis (scleroderma).

Matrix metalloproteinase 1 (MMP-1) is necessary for degradation of interstitial collagen types I, II, and III, which are the major constituents of the extracellular matrix (ECM). Increased expression of MMP-1 has been correlated with invasiveness of certain malignancies and cartilage degradation in rheumatoid arthritis. Increased transcriptional activity of MMP-1 has been reported with a single nucleotide polymorphism (SNP) of the MMP-1 promoter. Systemic sclerosis (SSc) is characterized by increased accumulation and turnover of collagen and other components of ECM. Previous studies have reported increased expression of MMP-1 transcripts in SSc fibroblasts. Therefore, we sought to determine if SSc patients with early disease (< or =5 years) from a multi-ethnic cohort were more or less likely than ethnically-matched normal controls to have an increased frequency of the high promoter activity MMP-1 genotype and whether MMP-1 promoter genotypes correlated with any of the major clinical manifestations of SSc. The results show that the frequency of the high activity promoter genotype in either the heterozygous or homozygous state did not differ significantly between SSc patients and ethnically-matched controls, or between SSc patients with either diffuse or limited scleroderma. Furthermore, MMP-1 promoter genotypes did not significantly correlate with any of the major clinical manifestations of SSc.

Humans↗
PubMed2001

Systemic sclerosis in 3 US ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants.

OBJECTIVE: To determine whether ethnic factors influence the presentation, serologic expression and immunogenetics of systemic sclerosis (SSc), patients from 3 ethnic groups were compared for clinical features, SSc-associated autoantibodies, and human leukocyte antigen (HLA) class II alleles. METHODS: Fifty-four Hispanics, 28 African Americans, and 79 whites from Texas with recent-onset (less than 5 years) SSc enrolled in a prospective longitudinal study were assessed for sociodemographic, clinical, immunologic, immunogenetic, behavioral, and psychologic parameters using validated instruments and standard laboratory techniques. Serologic and immunogenetic characteristics from these patients and larger retrospective SSc cohorts of the same ethnic groups also were examined. RESULTS: Hispanics and African Americans in the prospective cohort were more likely to have diffuse skin involvement, skin pigmentary changes, digital ulcers, pulmonary hypertension (African Americans), and an overall lower sociodemographic status than whites, who had more facial telangiectasia and hypothyroidism. In the larger combined prospective and retrospective groups of SSc patients, whites were likely to have more anticentromere antibodies (ACA) and African Americans more anti-U1-ribonucleoprotein (RNP) and anti-U3-RNP (fibrillarin) autoantibodies. HLA-DQB1*0301 was significantly associated with SSc per se in all 3 ethnic groups; HLA-DRB1*11 correlated with the anti-topoisomerase I antibody response, and HLA-DRB1*01, DRB1*04, and DQB1*0501 with ACA. CONCLUSIONS: Important sociodemographic, clinical, and serologic differences exist between whites, African Americans, and Hispanics, despite shared genetic (HLA class II) predisposing factors. The impact of these differences on prognosis remain to be determined.

Adult↗
PubMed2001

HLA-B27 and genetic predisposing factors in spondyloarthropathies.

With the mapping of the human genome having been completed, our ability to investigate and ideally better understand the genetic basis of rheumatic diseases is advancing at a rapid pace. Substantial evidence strongly favors a direct role for HLA-B27 in genetic susceptibility to ankylosing spondylitis and related spondyloarthropathies, although the underlying molecular basis has yet to be identified. HLA-B27 contributes only 16 to 50% of the total genetic risk for the disease, clearly indicating that other genes must be involved. However, no other putative disease genes have yet been absolutely proven. Potential genes include MHC (HLA class II, low molecular weight proteasome [LMP], transporter associated with antigen processing (TAP), tumor necrosis factor [TNF]-alpha, and major histocompatibility complex class I chain-related gene A (MICA), as well as non-MHC genes (IL-1RA, IL-6, IL-10, and CYP2D6). Genome-wide screens have identified other chromosomal areas of interest: 1p, 2q, 6p, 9q, 10q, 16q, and 19q. However, different studies have given conflicting results. HLA-B27 itself is a serologic specificity, which encompasses 25 different alleles that encode 23 different products (proteins): HLA-B*2701 to B*2723. These alleles may have evolved from the most widespread subtype, B*2705, and two of them, B*2706 in Southeast Asia and B*2709 in Sardinia, seem not to be associated with ankylosing spondylitis. The distinction between the disease associated and nonassociated subtypes may provide clues to the actual role of B27 in disease pathogenesis.

Genetic Predisposition to Disease↗