The influence of age, sex, and race on the upper reference limit of serum C-reactive protein concentration.

OBJECTIVE: The recommended reference range for serum C-reactive protein (CRP) concentrations is usually not adjusted for age and sex. We sought to determine if age, sex, and race or ethnicity influence the distribution of CRP values, and if upper reference limits of CRP should be adjusted by demographic factors. METHODS: Interviews, physical examinations, and blood draws were performed on > 22,000 individuals age > or = 4 yrs representative of the noninstitutionalized population of the United States, as part of the Third National Health and Nutrition Evaluation Survey (NHANES III). Serum CRP concentrations were measured by nephelometric immunoassay. RESULTS: The 95th percentile value of CRP in the overall population was 0.95 mg/dl for males and 1.39 mg/dl for females, and varied with age and race. For ages 25-70 yrs, the age adjusted approximate upper reference limit (mg/dl) was CRP = age/50 for males, and CRP = age/50 + 0.6 for females. The upper limits for Mexican-Americans and non-Hispanic whites were similar, whereas for non-Hispanic black adults the approximate upper limit was CRP = age/30 for males and CRP = age/50 + 1.0 for females. Even after accounting for identified inflammatory conditions, demographic factors influenced the reference limits of CRP. The 95th percentile values were uniformly lower in children than in older adults. CONCLUSION: Demographic factors, including age, sex, and race, should be used to adjust the upper reference limit for CRP. Clinicians should be aware of these factors when using CRP values to assess inflammatory diseases.

Clinicopathologic correlations in lupus nephritis in Lima, Peru.

BACKGROUND: We assessed whether immunohistologic markers for glomerular or tubulointerstitial injury might provide better correlations with ongoing renal function and disease activity as compared with the WHO classification or the NIH activity and chronicity indices in lupus nephritis. METHODS: Thirty-three patients with clinically defined systemic lupus underwent renal biopsy over a 1-year period at Hospital Loayza in Lima, Peru. Biopsy specimens were evaluated for macrophages, proliferating cells, alpha-actin expression, and type IV collagen deposition in both glomeruli and the tubulointerstitium and the results compared with the current WHO and NIH classifications in relation to the clinical presentation. RESULTS: Patients with WHO class IV lupus nephritis were more likely to have lower serum complements, greater proteinuria and hematuria, and worse renal function. An elevated NIH activity index correlated with microhematuria, proteinuria, and impaired renal function, whereas an elevated chronicity index correlated with renal function, hypertension, and microhematuria, but not with proteinuria. The presence of glomerular macrophages correlated with both glomerular alpha-actin expression and type IV collagen deposition, but did not correlate with renal function or proteinuria. In contrast, interstitial macrophages correlated not only with interstitial collagen deposition and myofibroblast accumulation, but also correlated with both renal function and the presence of nephrotic syndrome. CONCLUSIONS: Both the WHO classification and the NIH activity/chronicity indices correlate with clinical manifestations of lupus nephritis. While glomerular macrophage accumulation correlates with mesangial cell activation (alpha-actin expression) and collagen deposition, and interstitial macrophage accumulation correlates with interstitial fibroblast activation and collagen deposition, only interstitial macrophages correlate with renal function. Of particular interest will be future studies to determine whether these markers correlate with the prognosis.

Humoral and cellular immune response of adults from northeastern Brazil with chronic Trypanosoma cruzi infection: depressed cellular immune response to T. cruzi antigen among Chagas' disease patients with symptomatic versus indeterminate infection.

Infection with Trypanosoma cruzi can cause chronic Chagas' disease manifestations (cardiac, gastrointestinal), although most persons with chronic infection have no ill effects (indeterminate form). Cell-mediated immunity (CMI) responses are believed to be intrinsically important in the containment of T. cruzi and in the pathogenesis of Chagas' disease. Humoral and CMI responses were investigated in 70 T. cruzi-infected persons from an endemic area in northeastern Brazil and in 30 uninfected controls. An epidemiologic survey, physical examination, and blood evaluation were conducted for each subject. The 70 chronically infected persons were subclassified into three clinical groups: indeterminate, cardiac, and gastrointestinal. Serum was tested for antibodies to T. cruzi by hemagglutination assay, indirect immunofluorescent assay, and enzyme-linked immunosorbent assay, and for autoantibodies to tubulin. Serum levels of soluble interleukin-2 receptor (sIL-2R), albumin, and C-reactive protein (CRP) were also measured to assess one parameter each of immunosuppression, nutritional status, and inflammation. The proliferative response of peripheral blood mononuclear cells (PBMC) to T. cruzi antigens, mitogen (phytohemagglutinin), and antigen-free controls was also assessed. Our data did not reveal any significant differences in serum levels of antibodies to T. cruzi, antibodies to tubulin, albumin, CRP, or sIL-2R among the subgroups of infected individuals. The data demonstrate differences in CMI responses. Trypanosoma cruzi trypomastigote lysate stimulated proliferation of PBMC from infected persons, but not uninfected controls. Patients with symptomatic Chagas' disease (cardiac and gastrointestinal groups) had decreased cellular responses to T. cruzi lysate (median proliferation index [PI] = 3), compared with those in the indeterminate group (median PI = 9; P < 0.005). Further investigations of the mechanism of this reduced CMI response in those with chronic disease may yield insights into the pathogenesis of Chagas' disease.