The objective of this study is to examine the clinical features and outcomes of patients with systemic lupus erythematosus (SLE) whose disease began in adolescence [juvenile-onset SLE (jSLE)] compared with adult-onset patients [adult-onset SLE (aSLE)] from a large multiethnic cohort. Systemic lupus erythematosus patients of African-American, Caucasian, or Hispanic ethnicity and ≥1 year follow-up were studied in two groups: jSLE (diagnosed at ≤18 years); aSLE (diagnosed at 19-50 years; matched for gender and disease duration at enrolment). Sociodemographic data, SLE manifestations, disease activity, damage accrual, SLE-related hospitalizations or emergency room visits, drug utilization, mortality and psychosocial characteristics and quality of life were compared. Data were analysed by univariable and multivariable analyses. Seventy-nine patients were studied (31 jSLE, 48 aSLE); 90% were women. Mean (SD) total disease duration was 6.8 (2.7) years in jSLE and 5.6 (3.3) years in aSLE (p = 0.077). Mean age at cohort entry was 18.4 (1.8) and 33.9 (9.2) years in jSLE and aSLE respectively. By univariable analysis, jSLE patients were more commonly of African-American descent, were more likely to have renal and neurological involvements, and to accrue renal damage; jSLE patients had lower levels of helplessness and scored higher in the physical component measure of the SF-36 than aSLE patients. Renal involvement [OR = 1.549, 95% CI (1.397-15.856)] and neurological involvement [OR = 1.642, 95% CI (1.689-15.786)] were independently associated with jSLE by multivariable analysis. There was a larger proportion of African-Americans within the jSLE group. After adjusting for ethnicity and follow-up time, jSLE patients experienced more renal and neurological manifestations, with more renal damage. There was a two-fold higher mortality rate in the jSLE group.
Objective. To examine health disparities as a function of ethnicity using data from LUpus in MInorities, NAture versus nurture (LUMINA), a longitudinal study of patients with systemic lupus erythematosus (SLE); to build an explanatory model of how ethnic disparities occur in this setting; and to suggest appropriate interventions. Methods. LUMINA patients (meeting American College of Rheumatology criteria for SLE) ages >16 years of African American, Hispanic (from Texas), Hispanic (from Puerto Rico), or Caucasian ethnicity were studied. In addition to examining the basic features of the cohort, we examined, by univariable and multivariable analyses, the factors associated with disease activity, damage accrual, lupus nephritis, and mortality. An empiric model based on the data presented (and the literature reviewed) was derived to explain the disparities observed. Results. There were substantial differences in the socioeconomic/demographic, clinical, and genetic features among patients from the different ethnic groups, with Texan Hispanic and African American patients exhibiting overall a lower socioeconomic status, different genetic associations, more serious disease at a younger age, and worse intermediate and final outcomes than the Caucasian and Puerto Rican Hispanic patients. A model of disease outcome as a function of the disparities observed was created.Conclusion. Ethnic disparities occur in SLE. Environmental, socioeconomic/demographic, psychosocial, genetic, and clinical factors play an important role as determinants of the ethnic differences observed. Measures aimed at eliminating these disparities are suggested while further research is conducted to elucidate the basis of these disparities and their changes at the societal level and to eliminate the gap between the rich and the poor.
Intracellular replication of the protozoan parasite Trypanosoma cruzi inside macrophages is essential for the production of the disease and the development of the parasite. Two CD4+ T cell lines, A10 and A28, were established from T. cruzi-infected BALB/c mice which specifically proliferated to parasite antigens. The trypanocidal activity of BALB/c macrophages was induced upon culture with the A10, but not with the A28 T cell line. The cell-free supernatant from this A10 line, as well as from immune spleen cells stimulated with specific antigen or concanavalin A, but not from the A28 T cell line also activated the trypanocidal activity of peritoneal macrophages or of the J774 macrophage-like cell line. when the lymphokine content of the supernatants from both cell lines was analyzed, it was found that the A10 T cell line secreted interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha and interleukin 2, whereas the A28 line did not secrete IFN-gamma upon stimulation. Furthermore, the trypanocidal-inducing ability of A10 supernatant was completely abrogated by neutralizing anti-IFN-gamma antibodies and partially abrogated by neutralizing anti-TNF-alpha antibodies. When recombinant cytokines were added to J774 cells, IFN-gamma was able to induce significant trypanocidal activity whereas TNF-alpha was almost ineffective. However, TNF-alpha or lipopolysaccharide (LPS) showed a synergistic effect with IFN-gamma on macrophage activation. IFN-gamma triggered nitric oxide (NO) synthesis by J774 cells whereas TNF-alpha was almost ineffective. TNF-alpha and LPS were also synergistic with IFN-gamma in the NO production. Both the NO production and the trypanocidal activity in J774 cells induced by T cell supernatants or lymphokine combinations were inhibited by N-monomethyl-L-arginine, a competitive inhibitor of NO synthase activity. A good correlation between the levels of NO production and trypanocidal activity induced by different lymphokine preparations was found. Those results suggest that IFN-gamma and TNF-alpha, secreted by T. cruzi-immune T cells, are involved in the activation of the trypanocidal activity of mouse macrophages through an NO-dependent mechanism.
Objective. To determine the impact of the patient's sex on the manifestations and outcome of systemic lupus erythematosus (SLE).Methods. We studied SLE patients who were ages 16 years or older and had a disease duration of <5 years at the time of enrollment in the LUpus in MInorities, NAture versus nurture cohort, a multiethnic cohort consisting of Hispanic, African American, and Caucasian patients. Socioeconomic/demographic, clinical, and serologic features, as well as disease activity (by the Systemic Lupus Activity Measure, Revised) and damage accrual (by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) were compared between male and female patient groups. Multivariable analyses using male sex and damage accrual as dependent variables were then performed.Results. Sixty-three male SLE patients (10.2%) from all ethnic groups were included. The mean ages of the male and female patients were comparable. Factors that were either more frequent or tended to be more frequent among male SLE patients were Caucasian ethnicity, smoking, alcohol use, lupus anticoagulant (LAC) positivity, and renal involvement, whereas musculoskeletal involvement was less common. American College of Rheumatology criteria accrual time and disease duration were shorter in the male patients; damage was more common and of higher magnitude in this group. LAC positivity, shorter disease duration, and higher early damage scores were independently associated with male SLE. Male sex was a strong predictor of baseline damage, measured as a categorical variable (t-test ؍ 2.357, -standardized coefficient 0.113; P ؍ 0.019) or a continuous variable (hazard ratio 3.179 [95% confidence interval 1.999-5.056]; P < 0.001). Male sex was also positively associated with the development of damage over most of the course of the disease.Conclusion. Poorer long-term prognosis among men with SLE appears to be decisively determined by their accelerated development of damage, particularly early in the course of the disease.Systemic lupus erythematosus (SLE) is an autoimmune disease that occurs more frequently among women, predominantly during their childbearing years. Its wide range of clinical manifestations and its overall prognosis have been repeatedly differentiated by sex as well. Male SLE patients have been reported to develop more severe skin lesions (1-3), serositis (i.e., pericarditis and/or pleuritis) (2-5), renal involvement (5), thrombotic events (6), and seizures (7) as compared with
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