Plasma neutrophil gelatinase-associated lipocalin levels are markedly increased in patients with non-transfusion-dependent thalassemia: Lack of association with markers of erythropoiesis, iron metabolism and renal function.
BACKGROUND
Neutrophil Gelatinase-Associated Lipocalin (NGAL) (known as NGAL, Lipocalin 2, Siderocalin, Uterocalin, proteinase-3 and 24p3) is a mammalian small 25-kD peptide that belongs to the lipocalin superfamily, which consists of about 20 small lipoproteins. NGAL was initially discovered as an antibacterial factor of natural immunity and an acute-phase protein. NGAL is also an iron trafficking protein, a member of the non-transferrin-bound iron (NTBI) pool and an alternative to the transferrin-mediated iron-delivery pathway. Of note, NTBI, which is elevated in thalassemic patients, induces cellular toxicity. In this study we investigated the possible association of NGAL with parameters of erythropoiesis, iron metabolism and renal injury in patients with non-transfusion-dependent thalassemia (thalassemia intermedia or TI).


METHODS
Thirty-five patients with TI, 13 men and 22 women, aged 8-63 years, were included in the study, while, 20 healthy individuals served as controls. Plasma NGAL levels were determined using an immunoenzymatic technique. Erythroid marrow activity was estimated by measuring soluble transferrin receptors (sTfR) levels with a turbidimetric technique. NTBI levels were determined using electrothermal atomic absorption spectrometry. Cystatin C, β2-microglobulin and hs-CRP concentrations were measured by means of immunonephelometric techniques.


RESULTS
The main results of the study showed: a) NGAL levels were significantly higher in patients with TI compared to controls (139.1 ± 86.1 vs 51.2 ± 11.8 μg/L, p<0.0001), without significant effect of splenectomy or hydroxyurea on NGAL levels. Only 4 patients had NGAL levels within the control group range, b) no correlation was found between NGAL levels and either the parameters of erythropoiesis Hb, Hb F, reticulocytes and sTfR (p>0.66, p>0.67, p>0.63 and p>0.81 respectively), or with those of iron metabolism ferritin and NTBI (p>0.90 and p>0.95 respectively).


CONCLUSIONS
The increased NGAL levels reported for the first time in TI patients in this study are in agreement with the elevated expression of NGAL observed in TI mouse models. We postulate that the induction of NGAL in these patients may represent either a survival response, facilitating the survival of the less damaged thalassemic erythroid precursors, or a consequence of the abnormal iron regulation in TI.
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
Aikaterini
A
Patsaoura
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
Elizabeth
E
Tatsi
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
Alexandra
A
Margeli
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece.
Ino
I
Kanavaki
First Department of Pediatrics, Athens University Medical School, Athens, Greece.
Polyxeni
P
Delaporta
First Department of Pediatrics, Athens University Medical School, Athens, Greece.
Dimitra
D
Kyriakopoulou
Thalassemia Unit, Hematology Division, Department of Internal Medicine, Patras University Hospital, Patras, Greece.
Alexandra
A
Kouraklis-Symeonidis
First Department of Pediatrics, Athens University Medical School, Athens, Greece.
Antonios
A
Kattamis
Department of Clinical Biochemistry, "Aghia Sophia" Children's Hospital, Athens, Greece. Electronic address: biochem@paidon-agiasofia.gr.
Ioannis
I
Papassotiriou
D000209:Acute-Phase Proteins; D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D001803:Blood Transfusion; D002648:Child; D004920:Erythropoiesis; D005260:Female; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007677:Kidney Function Tests; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood*; D013789:Thalassemia / Q000097:blood*; D055815:Young Adult
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D007501:Iron
Erythropoiesis; Iron metabolism; Kidney injury; NGAL; Thalassemia intermedia