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

Psychosocial interviews with 2320 male survivors of acute myocardial infarction, participants in the beta-Blocker Heart Attack Trial, permitted the definition of two variables strongly associated with an increased three-year mortality risk. With other important prognostic factors controlled for, the patients classified as being socially isolated and having a high degree of life stress had more than four times the risk of death of the men with low levels of both stress and isolation. An inverse association of education with mortality in this population reflected the gradient in the prevalence of the defined psychosocial characteristics. High levels of stress and social isolation were most prevalent among the least-educated men and least prevalent among the best-educated. The increase in risk associated with stress and social isolation applied both to total deaths and to sudden cardiac deaths and was noted among men with both high and low levels of ventricular ectopy during hospitalization for the acute infarction.

Only a fraction (12%) of 268 "autoreactive" T cell clones derived from lupus-prone mice can selectively induce the production of pathogenic anti-DNA autoantibodies in vitro and accelerate the development of lupus nephritis when transferred in vivo. The CDR3 loops of T cell receptor beta chains expressed by these pathogenic T helper (Th) clones contain a recurrent motif of anionic residues suggesting that they are selected by autoantigens with cationic residues. Herein, we found that approximately 50% of these pathogenic Th clones were specific for nucleosomal antigens, but none of them responded to cationic idiopeptides shared by variable regions of pathogenic anti-DNA autoantibodies. Nucleosomes did not stimulate the T cells as a nonspecific mitogen or superantigen. Only the pathogenic Th cells of lupus responded to nucleosomal antigens that were processed and presented via the major histocompatibility class II pathway. Although the presentation of purified mononucleosomes to the Th clones could be blocked by inhibitors of endosomal proteases, neither of the two components of the nucleosomes--free DNA or histones by themselves-- could stimulate the Th clones. Thus critical peptide epitopes for the Th cells were probably protected during uptake and processing of the nucleosome particle as a whole. The nucleosome-specific Th clones preferentially augmented the production of IgG autoantibodies to histone-DNA complex in vitro. In vivo, nucleosome-specific, CD4+ T cells were not detectable in normal mice, but they were found in the spleens of lupus-prone mice as early as 1 mo of age, long before other autoimmune manifestations. Immunization of young, preautoimmune lupus mice with nucleosomes augmented the production of autoantibodies and markedly accelerated the development of severe glomerulonephritis. Previously, crude preparations containing nucleosomes were shown by others to have polyclonal mitogenic activity for B cells from normal as well as lupus mice. Identification here of pure mononucleosome as a lupus-specific immunogen for the Th cells that selectively help the pathogenic anti-DNA autoantibody producing B cells of lupus could lead to the design of specific therapy against this pathogenic autoimmune response.

To determine if differences in morbidity of systemic lupus erythematosus (SLE) as measured by (1) important renal disease, (2) number of hospitalizations, and (3) neurologic disease can be explained by race, socioeconomic status (SES), or measures of compliance. The interrelationship of black race, SES, and the physician's assessment of compliance as risk factors for morbidity was examined in a cohort of 198 patients with SLE (179 female, 115 black). SES was measured with Nam-Powers scores for education (years), income, and job status, and source of insurance; compliance was assessed by physician global assessment and percent of protocol visits kept. Morbidity outcomes were important renal disease (creatinine level 1.5 mg/dL or greater, renal failure, nephrotic syndrome), neurologic involvement, and number of hospitalizations. The Johns Hopkins Rheumatology Faculty Practice, in which both private and clinic patients are seen. Black patients had significantly lower SES on all measures (p less than 0.0001) and were also less compliant by physician global assessment (odds ratio [OR] = 0.39, p = 0.002). Univariate analyses showed that blacks had a higher frequency of important renal disease (OR = 2.07, 95% confidence interval [CI] 1.05 to 4.11) and hypertension (OR = 1.80, 95% CI 1.01 to 3.23). Important renal disease was associated with the physician global assessment of compliance (p = 0.009) and hypertension (p less than 0.001). Multiple regression models for important renal disease, including race, physician global assessment of compliance, hypertension, SES, age, and gender, identified significant associations with only physician global assessment of compliance (OR = 0.40, 95% CI 0.17 to 0.91) and hypertension (OR = 5.37, 95% CI 2.40 to 11.98); black race was not significant (OR = 1.60, 95% CI 0.68 to 3.76). The second morbidity measure, number of hospitalizations, was associated with renal disease, neurologic disease, mouth ulcers, duration of disease, and public insurance but not with black race, in the best log-linear model. Neither race, SES variables, nor physician assessment of compliance was significantly associated with neurologic disease, the third morbidity measure. These data fail to support an independent association of black race with morbidity in SLE; rather, they suggest that noncompliance (as measured by physician global assessment) and type of medical insurance are important factors in morbidity. Classical epidemiologic measures of SES (education, income, occupation) do not appear to be significant confounders of the relationship of race to morbidity in SLE.