Serum Ferritin Iron, a New Test, Measures Human Body Iron Stores Unconfounded by Inflammation

Abstract

Serum ferritin protein is an acute phase reactant. We hypothesized that serum ferritin protein generated in response to an inflammatory process would have much less iron (Fe) in it than would "normal" ferritin protein, and therefore measuring serum ferritin iron would assess human body iron status unconfounded by inflammation. We measured serum ferritin iron in 140 clinical samples obtained from the serum banks of Bronx VA Medical Center Hematology and Nutrition Laboratory (Bronx, NY), the CDC Nutritional Biochemistry serum sample bank (Atlanta, GA), and the sample bank from patients with thalassemia and iron overload treated at New York Hospital (New York, NY). Each was analyzed for three conventional criteria of iron status: serum iron, percentage of transferrin saturation and ferritin protein. In addition, tests for inflammation were also performed: C-reactive protein, WBC and transaminases. Seventy-seven patients' sera from 140 screened met each of three consistent criteria for stages of iron status. Serum ferritin was immobilized by immunoprecipitation with rabbit antihuman polyclonal antibody bound to agarose and separated from other iron-containing proteins, digested with 0.2 ml of 3N nitric acid and analyzed for iron content by atomic absorption spectroscopy. Serum ferritin iron ranged in normal controls from 10 ng to 35 ng Fe/ml. The patients with iron deficiency (4/4) and those in negative iron balance (5/6) had values < or = 10 ng. Positive iron balance (8/9) and iron overload (22/22) values were > 35 ng/ml, in contrast to 11/19 with inflammation. Seventeen of twenty-two with overload had values > 100 ng/ml while only 1/19 with inflammation had such a value. Ferritin iron in ferritin protein was > 15% by weight in 14/22 with iron overload but in 0/19 with inflammation. Serum ferritin iron is a simple, direct measure of iron stores that we propose, in conjunction with measuring serum ferritin protein, as a minimally invasive screening procedure for accurately assessing the whole range of human body iron status, unconfounded by inflammation.