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.

Systemic lupus erythematosus in three ethnic groups. XX. Damage as a predictor of further damage.

OBJECTIVE: To examine the predictors of damage in a multiethnic cohort of systemic lupus erythematosus (SLE) patients with a specific focus on damage at baseline. PATIENTS AND METHODS: SLE patients from a multiethnic US (Hispanic, African-American and Caucasian) cohort (LUMINA: Lupus in Minority populations, Nature versus nurture) were included if they had > or =6 months of follow-up in the cohort. Damage was measured with the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index (SDI). The dependent variable was the change in SDI score between study visits. Predictors were from the preceding visit. Variables known to affect damage accrual in SLE were included in the analyses. RESULTS: Three hundred and fifty-two patients (82 Hispanics, 153 African-Americans and 117 Caucasians) representing 1795 patient visits were included. Previous damage was found to be a significant predictor of subsequent damage accrual (P < 0.0001). Other variables predictive of subsequent damage accrual were disease activity (P < 0.0001), older age (P = 0.041) and use of corticosteroids (P = 0.0048). CONCLUSIONS: Once damage occurs in SLE, further damage is expected to occur. This is more likely to be the case if disease activity persists. These data have clinical implications for the management of SLE patients.

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.

Systemic lupus erythematosus in three ethnic groups: XV. Prevalence and correlates of fibromyalgia.

The purpose of this study was to determine the prevalence and correlates of fibromyalgia (FM) in a prospective, multiethnic systemic lupus (SLE) cohort. A total of 266 SLE patients with disease duration of < or = 5 years at study entry were evaluated longitudinally for the presence of FM (per ACR criteria). Sociodemographic factors, behavioral/psychological variables, clinical features, serologic factors (autoantibodies), and self-reported functioning (MOS SF-36) were ascertained in all patients. Subjects were evaluated at study entry and annually thereafter. The prevalence of FM was then calculated, as was the prevalence of FM-like manifestations (widespread pain with at least 6, but fewer than 11/18 tender points). Variables were evaluated for association with FM or FM-like manifestations by univariate and stepwise logistic regression analyses. FM was present in 14 patients (5%; 9/92 Caucasians (C), 4/109 African Americans (AA), 1/65 Hispanics (H)) and FM/FM-like manifestations in 35 (13%; 16 C, 9 AA, 10 H). There was no difference noted between those with and without FM with respect to gender, education level, income below poverty level, disease activity or damage. By stepwise logistic regression analyses, the strongest association with both FM and FM/FM-like manifestations was a self-reported history of anxiety or affective disorder (P = 0.0237, OR = 4.6 and P = 0.0068, OR = 3.4, respectively). Caucasian ethnicity was strongly associated with FM (P = 0.0066, OR = 7.5) and African American ethnicity was negatively associated with FM/FM-like (P = 0.0204, OR = 0.3). Poorer self-reported physical functioning was associated with FM/FM-like (P = 0.0443, OR = 0.96). FM and FM-like manifestations correlate best with the presence of Caucasian ethnicity, concomitant anxiety or affective disorder, and to a lesser extent with poorer self-reported physical functioning. African American ethnicity is negatively associated with the combination of FM and FM-like manifestations. Clinical measures of disease activity, disease damage, specific organ dysfunction, sociodemographic factors and serologic features are not correlated with FM in this early SLE cohort.

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.

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.

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.

The T lymphocyte structure CD60 contains a sialylated carbohydrate epitope that is expressed on both gangliosides and glycoproteins.

The CD60 antigen is expressed on a majority of T cells in autoimmune lesions, and anti-CD60 can activate T lymphocytes. CD60 has been defined as the GD3 ganglioside, and subsequently as the 9-O-acetylated form of GD3. However, other evidence suggests that anti-CD60 recognizes a glycoprotein or family of glycoproteins expressed by T lymphocytes. The current studies were undertaken to better define the identity of the CD60 antigen on both T cells and non-T cells. Treatment of intact cells with neuraminidases of various specificities confirmed that detection of the CD60 epitope depends on expression of an alpha2, 8-disialic acid carbohydrate linkage, as is found in GD3 and related gangliosides. However, the sialicacid polymer colominic acid inhibited anti-GD2 and anti-GD3, but not anti-CD60 from binding to cell surfaces. Expression of CD60 did not correlate with expression of GD3 on a variety of cell lines and T cell populations. Expression of CD60 and 9-O-acetyl-GD3 was roughly parallel on some non-T cell lines such as melanoma cells, but on T cells expression of CD60 was consistently greater. Antibodies to GD2, GD3 and 9-O-acetyl-GD3 were ineffective at inhibiting binding of anti-CD60 to CD60+ cells. Activation responses of T cells to anti-CD60 were inducible in either the presence or absence of a response to anti-GD3. A novel inhibitor of glucosyl ceramide synthesis, D-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (D-t-P4) reduced expression of GD3 much more than CD60 on activated T lymphocytes. Following biotinylation of HUT78 T cells, anti-CD60 immunoprecipitated a 70 kDa antigen. Taken together, the present data and previous findings suggest that anti-CD60 can recognize both a modified form of the GD3 ganglioside and a carbohydrate-dependent complex epitope present on one or more glycoproteins. This glycoprotein epitope may be the more abundant and functionally significant CD60 antigen on T lymphocytes, while 9-O-acetyl-GD3 is likely to be the principal structure recognized by anti-CD60 on melanoma cells. These findings emphasize the complexity of understanding the functional roles of carbohydrate epitopes in cell activation.

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.

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.

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.

Systemic lupus erythematosus in three ethnic groups. VI: Factors associated with fatigue within 5 years of criteria diagnosis. LUMINA Study Group. LUpus in MInority populations: NAture vs Nurture.

OBJECTIVE: To determine the frequency, degree and associated features of fatigue among Hispanic (H), African American (AA) and Caucasian (C) patients with recent onset (< or = 5 yr) systemic lupus erythematosus (SLE) at their baseline evaluation. METHODS: H (n = 69), AA (n = 83) and C (n = 71) patients from the LUMINA (LUpus in MInority populations: NAture vs Nurture) cohort were studied. Fatigue [Fatigue Severity Scale (FSS)] was defined as present if FSS score > or = 3.0. Variables from functional, clinical, sociodemographic, health behaviors, behavioral and psychological and immunogenetics domains were ascertained at study entry. Associations were examined using regression models. RESULTS: Eighty-six percent (85.7%) of patients reported having fatigue (82.6% H; 85.5% AA; 88.7% C); median FSS score, 5.3. Factors from the psychological and clinical domains were primarily associated with FSS; immunogenetic (HLA Class II phenotypes) features were not. Increased fatigue was strongly associated with decreasing function, both physical and mental. Variables associated with significantly greater degree of fatigue at baseline in the multivariable stepwise model in order of decreasing additional partial R2 explained included: abnormal illness-related behaviors, older age, higher self-reported pain, greater degree of helplessness, greater disease activity, Caucasian race, and lacking health insurance (model R2 = 37%). CONCLUSIONS: Fatigue is one of the most prevalent clinical manifestations of SLE across all ethnic groups. The perception of fatigue severity in SLE may be multifactorial in origin, including psychosocial factors and disease activity. If these prove causal, knowledge of their contribution may suggest therapeutic and/or behavioral interventions, which could ameliorate this pervasive and often incapacitating symptom of SLE.

Systemic lupus erythematosus in three ethnic groups: III. A comparison of characteristics early in the natural history of the LUMINA cohort. LUpus in MInority populations: NAture vs. Nurture.

AIM: To determine and contrast the socioeconomic-demographic and clinical features of patients with recent onset (< or =5 y) systemic lupus erythematosus (SLE) from three ethnic groups, Hispanic, African-American and Caucasian (H, AA, C). SUBJECTS AND METHODS: SLE cases (American College of Rheumatology criteria) (incident (n = 56), prevalent (n = 173)), were enrolled in a longitudinal study at The University of Alabama at Birmingham, The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston. Socioeconomic-demographic, clinical, immunological, behavioral and psychological data were obtained using validated instruments and standard laboratory techniques, and compared. RESULTS: 70 H, 88 AA and 71 C SLE patients constitute this cohort. H and AA patients were younger and of lower socioeconomic-demographic status. They also had evidence of more frequent organ system involvement (renal, cardiovascular), more auto-antibodies, more active disease (after adjusting for discrepant socioeconomic-demographic features), lower levels of social support and more abnormal illness-related behaviors (more in H than in AA). H also were more likely to have an abrupt disease onset; C were more likely to be on antimalarials but less likely to be on corticosteroids. H, AA, and C used health care resources comparably. They had similar levels of pain and physical and mental functioning after adjusting for age, disease duration, income, education, social support, illness-related behaviors, and Systemic Lupus Activity Measure or SLAM scores. CONCLUSIONS: H and AA patients have more active SLE, at an earlier age of onset, and a less favorable socioeconomic-demographic structure (worse among the H than AA) which predispose them to a less favorable natural history.

An overview of intermittent inotropic therapy for severe congestive heart failure.

Congestive heart failure (CHF) is a major problem in the field of medicine in the U.S. Over 4 million people in the U.S. have CHF with 400,000 new cases per year. This diagnosis creates 6 million hospital days with a Medicare cost of billions of dollars. There are limited options for patients >65 years of age who have resistant heart failure on maximum medical therapy. There is considerable debate surrounding intermittent inotropic therapy. This paper is a review of the literature regarding this form of therapy; 20 studies are described. All but one of these studies disclose beneficial effects. The major criticism of these studies is that they are small and not randomized or placebo controlled. Larger well controlled studies are needed to determine the effect and safety of this treatment. Researchers must develop and evaluate all forms of therapy fairly to help decrease hospitalizations, decrease mortality, and improve quality of life.

Systemic lupus erythematosus in three ethnic groups. IV. Factors associated with self-reported functional outcome in a large cohort study. LUMINA Study Group. Lupus in Minority Populations, Nature versus Nurture.

OBJECTIVE: To identify features of systemic lupus erythematosus (SLE) associated with poor functional outcome as measured by the 36-item Medical Outcomes Study Short Form 36 Health Survey (SF-36). METHODS: Two hundred twenty-four patients with early SLE (70 Hispanic, 83 African American, and 71 white) enrolled in a longitudinal study of outcomes were evaluated at study entry. The 8 composite scales and 2 summary measures (physical and mental) of the SF-36 were the dependent variables. Independent variables--1) sociodemographic, 2) clinical features, 3) immunologic, 4) global scores, and 5) behavioral/cultural--were examined for each of the scales and summary measures and for each ethnic group. Significant variables in these analyses were then used to construct models to determine their association with each of the scales and the 2 summary measures for the entire population and the 3 ethnic groups. RESULTS: Self-reported physical and mental functioning were most consistently associated with abnormal illness-related behaviors, helplessness, fatigue, and pain at study entry. Helplessness was more strongly associated with functioning in the Hispanics than in the African American or white patients. Pain was strongly associated with physical but not mental health. The models were quite robust, accounting for 41% to 68% of the variance for the two summary measures. CONCLUSION: Patients' attitudes toward their disease, fatigue, and pain have greater impact on self-perceived functional levels, as measured by the SF-36, than do more objective measures of disease activity and damage such as the presence of specific autoantibodies and/or the occurrence of specific organ involvement. Interventions designed to improve outcome may need to include ethnic-specific as well as general strategies.

Systemic lupus erythematosus in three ethnic groups: I. The effects of HLA class II, C4, and CR1 alleles, socioeconomic factors, and ethnicity at disease onset. LUMINA Study Group. Lupus in minority populations, nature versus nurture.

OBJECTIVE: To study the relative impact of immunogenetic versus socioeconomic factors on systemic lupus erythematosus (SLE) at disease onset/presentation. METHODS: Medical records regarding SLE onset/ presentation were abstracted on 229 SLE patients who were enrolled in a prospective lupus outcome study. Patients were grouped in equivalent proportions of Caucasians, African Americans, and Hispanics. HLA-DRB1, DQA1, and DQB1 oligotyping, as well as C4 and CR1 allotyping, were carried out by standard methods. In addition to these genetic factors, data on ethnicity, age at SLE onset, monthly income, level of education, and home ownership were entered into stepwise logistic or stepwise multiple linear regression models as independent variables, and each specific clinical feature (neurologic, renal, and cardiovascular disease due to SLE), as well as the total Systemic Lupus Activity Measure (SLAM) score and physician's global assessment of disease activity at disease onset, were entered as dependent variables. RESULTS: HLA-DRB1*0301 (DR3), DRB1*1503 (DR2), and DRB1*08 (DR8) alleles were more frequently found in Caucasians, African Americans, and Hispanics, respectively. Hispanics were more likely to have cardiac and renal disease, as well as a higher physician's global assessment of disease activity. African Americans were more likely to have neurologic disease, renal disease, and a higher SLAM score. Those with less education had a higher SLAM score. Patients with HLA-DRB1*01 had less renal disease and a lower SLAM score. Those with C4A*3 alleles had a higher SLAM score and a higher physician's global assessment of disease activity. CONCLUSION: Both genetic and socioeconomic determinants, as well as other factors associated with Hispanic and African-American ethnicity, affect the presentation of SLE.

Systemic lupus erythematosus in three ethnic groups: II. Features predictive of disease activity early in its course. LUMINA Study Group. Lupus in minority populations, nature versus nurture.

OBJECTIVE: To determine the factors associated with disease activity in patients with recent-onset (< or =5 years) systemic lupus erythematosus (SLE) who were of Hispanic, African-American, or Caucasian ethnicity. METHODS: Incident and prevalent cases of SLE, as defined by the American College of Rheumatology criteria for SLE, among the 3 ethnic groups were identified in Alabama (The University of Alabama at Birmingham) and Texas (The University of Texas-Houston Health Science Center and The University of Texas Medical Branch at Galveston). Variables from the sociodemographic, clinical, immunologic, immunogenetic, behavioral, and psychological domains were obtained using validated instruments. Disease activity was ascertained with the Systemic Lupus Activity Measure (SLAM). Stepwise domain regressions with SLAM score as the dependent variable were performed. Final ethnic-specific and overall regression models were obtained by entering variables that were retained in the domain regressions. RESULTS: SLAM scores at study entry were higher in the African Americans (mean +/- SD 12.6 +/- 6.9) and Hispanics (11.0 +/- 6.2) than in the Caucasians (8.5 +/- 3.7) (P < or = 0.001). The final overall regression model (R2 = 28%) for higher SLAM score included the following variables: African-American ethnicity, lack of private health insurance, abrupt disease onset, presence of anti-Ro antibodies, absence of HLA-DRB1*0301, higher levels of helplessness, and abnormal illness-related behaviors. CONCLUSION: Socioeconomic, immunologic, immunogenetic, behavioral, and psychological variables were all predictive of disease activity early in the course of SLE, irrespective of ethnic group. However, there remain ethnic group differences in disease activity that were not explained by these factors.

Monocyte-dependent regulation of T lymphocyte activation through CD98.

CD98 is a 125 kDa heterodimer, which is strongly expressed on the surface of activated and proliferating cells. Its expression is strikingly regulated during T cell differentiation and activation, but the role of CD98 during T lymphocyte responses is not yet understood. We report here that proliferation of resting peripheral blood mononuclear cells (PBMC) induced by lectin, superantigen (SAg) or conventional antigens was blocked by anti-CD98 heavy chain (CD98hc) mAb. In contrast, anti-CD98hc did not block responses of T cell clones or lines. Anti-CD98hc inhibited IL-2 receptor expression and progression of T cells from G1 to S phase, but did not reduce expression of the IL-2 gene. Anti-CD98hc mAb did not regulate the initial activation events involving the TCR and co-receptor structures, but instead inhibited T lymphocyte responses even when added 18 h or more after the activation stimulus. Further experiments demonstrated that anti-CD98 was not directly affecting T cells in this system, but was instead acting on accessory cells. This was supported using a novel xenogeneic system that takes advantage of the lack of xenoreactivity of purified human T cells against mouse splenocytes. Despite absence of a direct xenoresponse to murine spleen cells, human T cells were activated by SAg presented by murine splenic antigen-presenting cells (APC). Murine anti-human CD98hc did not block T cell proliferation in this system. Furthermore, responses using monocyte-depleted PBMC as APC were not blocked by anti-CD98hc. Taken together, the present data suggests that triggering of human monocyte CD98 can suppress T cell proliferation by a process that halts progression through the cell cycle of recently activated T lymphocytes. This may represent a novel pathway for monocyte regulation of T cell activation.