Review
Serum ferritin: Past, present and future

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Abstract

Background

Serum ferritin was discovered in the 1930s, and was developed as a clinical test in the 1970s. Many diseases are associated with iron overload or iron deficiency. Serum ferritin is widely used in diagnosing and monitoring these diseases.

Scope of review

In this chapter, we discuss the role of serum ferritin in physiological and pathological processes and its use as a clinical tool.

Major conclusions

Although many aspects of the fundamental biology of serum ferritin remain surprisingly unclear, a growing number of roles have been attributed to extracellular ferritin, including newly described roles in iron delivery, angiogenesis, inflammation, immunity, signaling and cancer.

General significance

Serum ferritin remains a clinically useful tool. Further studies on the biology of this protein may provide new biological insights.

Section snippets

Historical perspective

Ferritin was discovered in 1937 by the French scientist Laufberger, who isolated a new protein from horse spleen that contained up to 23% by dry weight of iron [1]. The appearance of ferritin in human serum was documented several years thereafter [2]. However, quantification of serum ferritin awaited the purification of ferritin and anti-ferritin antibodies and the development of sensitive immunoassay techniques. In 1972, using an immunoradiometric assay, Addison et al. convincingly

Serum ferritin: basic biology

Ferritin is present in most tissues as a cytosolic protein, although a mitochondrial form has recently been described [6], [7] and nuclear localization and functions have been proposed [8], [9]. Ferritin plays an important role in the storage of intracellular iron, and has been the subjective of extensive recent reviews [10], [11], [12], [13]. Ferritin is a 24-subunit protein that is composed of two types of subunits, termed H and L. H refers to the original isolation of isoforms of ferritin

Extracellular ferritin in physiological and pathological processes

Due to difficulties in isolating serum ferritin in quantity, few if any experiments have directly assessed effects of exogenous administration of serum ferritin. However, several investigators have studied the effects of exogenous tissue ferritin on cells. It is uncertain whether this accurately models serum ferritin, or whether it instead models paracrine effects of ferritin released from adjacent cells. Despite this uncertainty, several interesting observations have been made using tissue

Ferritin as a clinical tool

Ferritin is a valuable tool for the clinician, both for the evaluation of common disease states, such as iron deficiency anemia, and for evaluation of hereditary and acquired iron overload conditions, such as hereditary hemochromatosis and chronic transfusion therapy. Serum ferritin is usually part of panel of several blood tests routinely ordered to diagnose and manage these conditions, and is arguably the single most useful marker in most populations, though some caveats apply, as discussed

Future directions

Despite its clear utility as a clinical tool to assess body iron stores, much of the biology of serum ferritin remains as elusive today as when it was first discovered. For example, cellular mechanisms involved in the secretion of ferritin, which does not contain a canonical leader sequence, remain unknown. This will be important to unravel, particularly as it is becoming clear that extracellular ferritin can subsume many functions unrelated to its classic role as an intracellular iron storage

Acknowledgements

This work was supported in part by grants from the National Institutes of Health (R37 DK42421, FMT; R01DK71892, SVT).

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