Measurements of iron status and survival in African iron overload.

INTRODUCTION: Dietary iron overload is common in southern Africa and there is a misconception that the condition is benign. Early descriptions of the condition relied on autopsy studies, and the use of indirect measurements of iron status to diagnose this form of iron overload has not been clarified. METHODS: The study involved 22 black subjects found to have iron overload on liver biopsy. Fourteen subjects presented to hospital with liver disease and were found to have iron overload on percutaneous liver biopsy. Eight subjects, drawn from a family study, underwent liver biopsy because of elevated serum ferritin concentrations suggestive of iron overload. Indirect measurements of iron status (transferrin saturation, serum ferritin) were performed on all subjects. Histological iron grade and hepatic iron concentration were used as direct measures of iron status. RESULTS: There were no significant differences in either direct or indirect measurements of iron status between the two groups. In 75% of these subjects the hepatic iron concentration was greater than 350 micrograms/g dry weight, an extreme elevation associated with a high risk of fibrosis and cirrhosis. Serum ferritin was elevated in all subjects and the transferrin saturation was greater than 60% in 93% of the subjects. Hepatomegaly was present in 20 of the 22 cases and there was only a moderate derangement in liver enzymes except for a tenfold increase in the median gamma-glutamyl transpeptidase concentration. There was a strong correlation between serum ferritin and hepatic iron concentrations (r = 0.71, P = 0.006). After a median follow-up of 19 months, 6 (26%) of the subjects had died. The risk of mortality correlated significantly with both the hepatic iron concentration and the serum ferritin concentration. CONCLUSIONS: Indirect measurements of iron status (serum ferritin concentration and transferrin saturation) are useful in the diagnosis of African dietary iron overload. When dietary iron overload becomes symptomatic it has a high mortality. Measures to prevent and treat this condition are needed.

Mucosal immune responses to intestinal bacterial pathogens.

Current advances in the study of gut mucosal immunology and molecular biology have enhanced our ability to understand the pathogenesis of enteric bacterial infections as well as the role of the immune system in mediating both tissue injury and protection. In this article, we review the immunopathogenesis and the protective immune response to three enteric pathogens, Vibrio cholerae, Shigella, and Salmonella. Each of these pathogens has a distinctive mechanism by which it causes disease, ie, epithelial attachment, epithelial invasion, and epithelial invasion with systemic dissemination. Pathogenicity and immune response can be conceptualized in terms of the interaction of these enteric pathogens with the gut epithelial compartment, immune inductive sites (Peyer's patch of the small intestine and lymphoid follicles of the colon), and a common immune effector compartment in the laimina propria where protective antibody is secreted. V cholerae, the representative noninvasive pathogen, has fimbrial adhesins that mediate attachment and colonization of the luminal surface of epithelial cells where organisms secrete cholera toxin (CT), a potent enterotoxin that induces a voluminous diarrhea via adenylate cyclase-dependent chloride secretion. Protective immunity is based on secretory (s) immunoglobulin A directed against whole-cell components that prevent attachment to gut epithelial cells and is enhanced by CT, an immunogen with potent adjuvant activity. Shigella, an enteric pathogen that locally invades gut epithelium, subverts the usual mechanism of immune sampling by initially invading via M cells overlying inductive sites. Subsequent macrophage invasion induces apoptosis and the release of interleukin-1, a proinflammatory cytokine. This seems to be a critical initiating event in immune-mediated tissue injury. Protective immunity is serotype specific. Infection caused by Salmonella is characterized by mucosal invasion and systemic spread mediated by the organisms ability to survive within macrophages. Both antibody and cell-mediated immunity are important for protection against Salmonella.

HLA-linked hemochromatosis and other forms of iron overload.

Inherited forms of iron overload are common. HLA-linked hemochromatosis and possibly African iron overload are associated with a significant risk of developing hepatocellular carcinoma. Early diagnosis and treatment, before substantial iron overloading occurs, reduces morbidity and mortality. HLA-linked hemochromatosis is easily diagnosed, and routine screening in European-derived populations may be appropriate.