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.Basic Methods. 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.Results. 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 ≤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.Implications of the Work. 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.

Molecular analyses of patients with hyperferritinemia and normal serum iron values reveal both L ferritin IRE and 3 new ferroportin (slc11A3) mutations

“…The measurement of ferritin iron has been proposed as a test to discriminate between elevated serum ferritin levels because of iron overload or because of inflammation. 34 This test may also discriminate patients with HHCS and those with ferroportin mutations, because serum ferritin iron content is likely to be low in patients with HHCS and elevated in patients with ferroportin mutations, although this finding remains to be demonstrated. Figure 3.…”

Interpreting indicators of iron status during an acute phase response – lessons from malaria and human immunodeficiency virus

“…Other approaches for assessing iron deficiency, especially in the presence of infection, include: † Determination of serum ferritin plus percentage saturation of serum iron-binding capacity (transferrin), where high serum ferritin plus a percentage transferrin saturation ,45 usually indicates infection caused the high ferritin; 44 † Measurement of sTfR, thought to be unaffected by infection; 45 † Measurement of sTfR plus ferritin.…”

Serum Ferritin, Insulin Resistance, and Metabolic Syndrome: Clinical and Laboratory Associations in 769 Non-Hispanic Whites Without Diabetes Mellitus in the HEIRS Study

“…SF is a mixture of iron-rich ferritin and apoferritin. 34,35 Iron-rich SF is in equilibrium with body iron stores. 36,37 The iron composition of SF is increased in hemochromatosis and other iron overload disorders, consistent with the function of ferritin as an iron storage protein.…”

“…36,37 The iron composition of SF is increased in hemochromatosis and other iron overload disorders, consistent with the function of ferritin as an iron storage protein. 5,34 Because the liver is a major iron storage organ, the iron content of SF in non-iron liver disorders associated with hepatocellular necrosis is also increased, presumably due to the release of intracellular iron-rich ferritin into the blood. 5,34,35 Ferritin released into the blood as an acute-phase reactant due to inflammation, anemia of chronic disease, or malignancy is typically apoferritin and has low iron content, 5,34,35 especially ferritin molecules released from cells or tissues that do not typically store iron.…”