Soluble Transferrin Receptor Concentrations Research Articles

Correlaton between soluble transferrin receptor concentration and inflammatory markers

Purpose: The concentration of soluble transferrin receptor (sTfR) is estimated as an iron parameter to evaluate erythropoiesis and iron status. The aim of our study is to evaluate the correlation between sTfR concentration and inflammatory parameters and to distinguish iron deficiency anemia from anemia of inflammation. Methods: One hundred and forty-four infants younger than two years of age who visited Gyeongsang University Hospital for 7 years from 2000 to 2006 were enrolled. Patients who had hemoglobin (Hb) <11 g/dL and ferritin <12 mg/L were excluded. Routine hematologic lab, serum ferritin, sTfR, and inflammatory markers [C-reactive protein(CRP), interleukin-6(IL-6), and absolute neutrophil count (ANC)] were investigated. Results: In all patients, the sTfR concentration showed a correlation with Hb, ferritin, MCV, and ANC, but not with CRP and IL-6. In multiple regression models, positive correlations were found between sTfR concentration and IL-6 (r=0.078, P=0.043), and negative correlations were found between sTfR concentration and ANC (r=-0.117, P=0.033) and MCV (r=-0.027, P=0.009). Conclusion: sTfR concentration was influenced by inflammatory parameters. Therefore, sTfR does not appear to be a useful parameter for discriminating between iron deficiency anemia and anemia of inflammation in infants. (Korean J Pediatr 2009;52:435-440)

Study of Circulating Prohepcidin in Association with Insulin Sensitivity and Changing Iron Stores

Liver synthesizes hepcidin in response to iron overload, leading to down-regulation of duodenal iron absorption. The pathophysiology of type 2 diabetes is associated with increased iron stores. We aimed to study circulating prohepcidin in association with insulin sensitivity and parameters of glucose and iron metabolism. Serum prohepcidin was evaluated in three cohorts: 1) a cross-sectional study (cohort 1, men from the general population; n = 135); 2) after decreasing iron stores in men with "high-ferritin" type 2 diabetes (cohort 2; n = 13); and 3) after decreasing iron stores in men carrying HFE gene mutations (cohort 3; n = 16). Insulin sensitivity was measured using either the minimal model or the clamp technique. Circulating prohepcidin correlated significantly with glycated hemoglobin (P < 0.0001), fasting glucose (P = 0.002), triglycerides (P = 0.007), high-density lipoprotein-cholesterol (P = 0.01), ferritin (P = 0.01), and soluble transferrin receptor concentration (P = 0.001) in subjects from cohort 1. Prohepcidin decreased significantly after iron depletion in patients with type 2 diabetes (P = 0.04) (cohort 2) and in carriers of HFE gene mutations (P = 0.03) (cohort 3). In the latter subjects, the change in serum prohepcidin after iron depletion was associated with the change in both fasting glucose transferrin (r = 0.58; P = 0.02) and saturation (r = 0.68; P = 0.005). The changes in insulin sensitivity were associated with those of liver iron content (r = -0.64; P = 0.007) and with those of serum prohepcidin (r = -0.50; P = 0.04) (cohort 3). These associations suggest that circulating prohepcidin concentration is pathophysiologically associated with parameters of glucose and iron metabolism. A failure to increase prohepcidin synthesis is hypothesized to contribute to iron-induced disorders of glucose metabolism.

Serum soluble transferrin receptor concentrations are increased in central obesity. Results from a screening programme for hereditary hemochromatosis in men with hyperferritinemia

Background A decrease in the serum concentrations of the soluble transferrin receptor (sTfR) is considered a good index of tissue iron. Because obesity is associated with hyperferritinemia and this is considered a sign of iron overload, a decrease in sTfR would be expected for the obese. We evaluated whether obese men with hyperferritinemia, detected in a genetic screening programme for hereditary hemochromatosis (HH), have lower serum concentrations of sTfR than their non-obese counterparts. Methods 75 men (age: 55.4 ± 12.4 years) with hyperferritinemia (serum ferritin — SF > 200 μg/L) and no known conditions of iron overload were evaluated for body mass index (BMI), waist circumference (WC), blood pressure, traditional indices of iron status, sTfR, fasting plasma glucose, lipid profile, insulin resistance (HOMA-IR), highly-sensitive C-reactive protein, hepatic enzymes and HFE gene mutations of HH. Results sTfR correlated with BMI ( r = 0.289; p = 0.014) and with WC ( r = 0.420; p < 0.001). Thirty-two subjects were obese (BM ≥ 30 kg/m 2) and had a significantly higher sTfR (2.95 (2.22–3.28) vs 2.28 (1.88–2.91) mg/L; p = 0.013), hemoglobin (157 ± 12 vs 152 ± 11 gr/L; p = 0.049) and HOMA-IR (1.38 (1.04–2.69) vs 1.02 (0.60–1.55) mg/L; p = 0.009) than the non-obese. WC explained separately more variability of the sTfR than BMI ( r 2 = 0.177; p = 0.002 and r = 0.077; p = 0.042, respectively), after adjusting for potential confounders. Conclusion An increase in serum concentrations of sTfR is associated with central obesity in men with hyperferritinemia.

Blood Loss Is a Stronger Predictor of Iron Status in Men Than C282Y Heterozygosity or Diet

Objective: To determine the relative importance of HFE gene, diet, lifestyle, and blood loss characteristics for predicting iron status in a sample of men aged 40 years or over.Design: Iron status (serum ferritin, transferrin saturation, soluble transferrin receptor) was measured in 44 C282Y heterozygote and 85 age- and BMI-matched wildtype men aged 40 years or over. Dietary intake of iron (total, heme and non-heme), and components known to influence iron bioavailability, was determined using a validated Meal-Based Intake Assessment Tool. Information on lifestyle and blood loss was obtained by questionnaire. Height and weight were measured to determine Quetelet's body mass index. Linear mixed models were used to determine the extent to which these variables predicted iron status.Results: C282Y heterozygosity was associated with 17% higher transferrin saturation (95% CI: 6%, 29%) but no difference in serum ferritin or soluble transferrin receptor concentrations. Blood donation was negatively associated with transferrin saturation (−13% (− 3%, −22%)) and serum ferritin (−58% (−44%, −68%)), and had a marginally significant positive association with soluble transferrin receptor concentration. Self-reported fecal blood loss was negatively associated with serum ferritin concentration (−35% (−54%, −7%)). Alcohol was the only dietary variable associated with iron status and was associated with all three of the iron status indices. Serum ferritin concentration was positively associated with body mass index (10% per unit increase (6%, 15%)).Conclusions: Blood loss was a stronger predictor of iron status than either C282Y heterozygosity or diet in this population of men aged 40 years and over.

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

Iron status is influenced by inflammation when the normal control of iron metabolism is reorganized by the primary mediators of the acute phase response, tumour necrosis factor-alpha and interleukin-1. The objective of this review is to show how indices of iron status, particularly haemoglobin, serum ferritin and soluble transferrin receptor concentrations relate to changes in the acute phase proteins during inflammation. The pattern of acute phase response after elective surgery, not preceded by infection, is used to demonstrate the time course of stimulation of the acute phase proteins. The changes in the concentrations of serum acute phase protein and markers of iron status during treatment for infection are used to demonstrate inter-relationships between the indicators. In many developing countries, asymptomatic malaria and human immunodeficiency virus (HIV) are common and may affect the interpretation of iron indicators during population assessments. Malaria produces an acute phase response and relationships between acute phase protein and indices of iron status indicate an influence of inflammation in both symptomatic and asymptomatic malaria, except when the parasitaemia is less than 1000/microL of blood when ferritin appears to be unaffected. HIV-1 impacts on haemopoiesis and anaemia. Anaemia increases in severity as the disease progresses and it is often a negative prognostic indicator. However, in individuals infected with HIV there may be an atypical acute phase response in the absence of opportunistic infections. Tentative conclusions are drawn concerning the inter-relationships between ferritin and the acute phase proteins, C-reactive protein and alpha-1-acid glycoprotein during an acute phase response.

Cytokine Concentrations in Bone Marrow of Stable Sickle Cell Anemia Patients

Inflammation plays a significant role in the clinical manifestations of sickle cell anemia. In studies of anemic patients with other clinical syndromes, measurement of the concentrations of cytokine mediators of...

Features of iron deficiency anemia without increment in soluble transferrin receptor concentration

Features of iron deficiency anemia without increment in soluble transferrin receptor concentration

Multi-micronutrient Sprinkles including a low dose of iron provided as microencapsulated ferrous fumarate improves haematologic indices in anaemic children: a randomized clinical trial.

Home-fortification of complementary foods with micronutrients (including iron) as Sprinkles is a new strategy to control iron deficiency and anaemia in developing countries. However, the most effective dose and form of iron is not known. The purpose of this study was to compare the efficacy of various doses (12.5, 20 or 30 mg) and treatment methods (multi-micronutrient Sprinkles vs. ferrous sulphate drops) on haemoglobin (Hb) concentration after 8 weeks of treatment in anaemic children. In total, 133 anaemic Ghanaian children (Hb 70-99 g L(-1)) aged 6-18 months were randomly assigned to one of five daily interventions for 8 weeks. Out of the five interventions, four used Sprinkles, and one used iron drops. Of the four Sprinkles groups, three included 12.5, 20 or 30 mg of iron as ferrous fumarate, and one included 20 mg of iron as ferric pyrophosphate. The iron drops group included 12.5 mg of iron as liquid ferrous sulphate. Hb concentrations were measured at baseline, week 3 and week 8. The primary outcome measure was Hb concentration at 8 weeks after treatment. We compared differences in Hb and ferritin concentrations and prevalence of iron deficiency anaemia (Hb < 100 g L(-1) and soluble transferrin receptor concentrations >8.5 mg L(-1)) from baseline to 8 weeks within and between groups. Adherence and reporting of side effects (staining of the teeth, ease of use, diarrhoea and darkening of stools) were compared between groups. Mean change in Hb was 1.4 g L(-1) (SD = 1.8) (P = 0.0001). Change in Hb concentrations from baseline to 8 weeks was significant in all groups (P = 0.0001-0.0007), with no differences across groups. Geometric means of serum ferritin varied from 18.6 to 44.0 microg L(-1) at baseline. At week 8, these means were in the interval of 48.0-78.3 microg L(-1), with no group differences. Prevalence of iron deficiency anaemia decreased significantly from baseline to 8 weeks in all groups with the exception of the iron drops group, with no group differences. Adherence was lower in the drops group (64%) as compared with Sprinkles groups (84%). Greater staining of the teeth and less ease of use were reported in the drops group as compared with Sprinkles groups. A dose as low as 12.5 mg of iron as ferrous fumarate when provided as Sprinkles may be effective in anaemic children.

Seasonal Childhood Anaemia in West Africa Is Associated with the Haptoglobin 2-2 Genotype

BackgroundAnaemia is a major cause of morbidity and mortality for children in Africa. The plasma protein haptoglobin (Hp) binds avidly to free haemoglobin released following malaria-induced haemolysis. Haptoglobin polymorphisms result in proteins with altered haemoglobin-binding capacity and different antioxidant, iron-recycling, and immune functions. Previous studies examined the importance of haptoglobin polymorphism in malaria and iron homeostasis, but it is unknown whether haptoglobin genotype might be a risk factor for anaemia in children in a malaria-endemic area.Methods and FindingsA cohort of 780 rural Gambian children aged 2–6 y was surveyed at the start and end of the malaria season. Samples were taken to assess haemoglobin (Hb) concentration, iron status (ferritin, zinc protoporphyrin, transferrin saturation, and soluble transferrin receptor concentration), haptoglobin concentration, α-1-antichymotrypsin (a measure of inflammation), and malaria parasites on blood film. We extracted DNA and genotyped for haptoglobin, sickle cell, and glucose-6-phosphate (G6PD) deficiency. Mean Hb levels fell over the malaria season. Children with the haptoglobin 2-2 genotype (17%) had a greater mean drop in Hb level over the malaria season (an 8.9 g/l drop; confidence interval [CI] 5.7, 12.1) compared to other children (a 5.1 g/l drop; CI 3.8, 6.4). In multivariate regression analysis, controlling for baseline Hb level, age group, village, malaria parasites on blood film, iron status, haptoglobin concentration, and G6PD deficiency, haptoglobin genotype predicted Hb level at the end of the malaria season ( p = 0.0009, coefficient = −4.2). Iron status was not influenced by haptoglobin genotype. ConclusionsThe finding that haptoglobin 2-2 genotype is a risk factor for anaemia in children in a malaria-endemic area may reflect the reduced ability of the Hp2-2 polymer to scavenge free haemoglobin-iron following malaria-induced haemolysis. The magnitude of the effect of haptoglobin genotype (4 g/l Hb difference, p = 0.0009) was comparable to that of G6PD deficiency or HbAS (3 g/l difference, p = 0.03; and 2 g/l difference, p = 0.68, respectively).

Intravascular Hemolysis and Mean Red BloodCell Age in Athletes

Since the observation that mechanical stress causes red blood cell (RBC) destruction, foot-strike hemolysis has been used to explain sports anemia and RBC rejuvenation in athletes. Recently gained knowledge questions the importance of mechanical RBC trauma on RBC hemolysis in athletes. Male athletes (N = 90) and untrained male controls (N = 58) were investigated for aerobic performance, hematological parameters, serum erythropoietin concentration (EPO), soluble transferrin receptor concentration (sTFR), and erythrocyte aspartate aminotransferase activity (eAST). On hard floor running disciplines (HFR, N = 26, short- and long-distance runners, triathletes) showed a lower eAST (P < 0.001) and thus no younger RBC population than not on hard floor running athletes (NHFR, N = 64, cyclists, soccer players, others) or the untrained control group (N = 58). HFR had higher but still normal EPO (P < 0.01) and no higher sTFR. Because intravascular hemolysis occurs in swimmers, cyclists, and runners, and mean RBC age is not reduced in runners, mechanisms other than foot-strike hemolysis have to be considered as well. Possible reasons are intramuscular destruction, osmotic stress, and membrane lipid peroxidation caused by free radicals released by activated leukocytes. Intravascular hemolysis can even be regarded as physiological means to provide heme and proteins for muscle growth.

A Phase I, Single and Fractionated, Ascending Dose Study Evaluating the Safety, Pharmacokinetics, Pharmacodynamics, and Immunogenicity of an Erythropoietic Mimetic Antibody Fusion Protein, CNTO528, in Healthy Male Subjects.

Objectives: To assess the safety, pharmacokinetics (PK), pharmacodynamics and immunogenicity of single and fractionated IV doses of an erythropoietic mimetic antibody fusion protein, CNTO 528, in healthy males.Methods: In this randomized, single-blind, and placebo (PBO)-controlled study, 44 subjects were enrolled in 5 dose cohorts. In Stage 1, 35 subjects received a single IV administration of 0.03, 0.09, 0.3, 0.9 mg/kg CNTO 528 or PBO. In Stage 2, 9 subjects received fractionated IV administrations of CNTO 528 or PBO on Days 1, 3 and 5 (3 infusions of 0.09 mg/kg or PBO).Results:Pharmacodynamics: In subjects treated with IV CNTO 528, a dose dependent increase in reticulocyte counts was observed. The maximum effect occurred at day 8 and returned back to baseline between days 22 through 29. Hemoglobin (Hgb) concentration increased in a dose dependent manner with a maximum effect occurring at day 22. Mean Hgb concentration remained 0.4 g/dL above baseline values at the last measurement, approximately 2.5 months after a single dose administration. A dose dependent increase in RBC count was observed with all RBC indices (MCV, MCH, MCHC) within normal range, indicating an increase in normocytic, normochromic RBCs. In all CNTO 528 treated subjects, a dose-dependent increase in soluble transferrin receptor concentration was observed. A dose-dependent increase in endogenous EPO concentration was observed, followed by a dose dependent decrease in endogenous EPO concentration. This may be the result of a competitive receptor binding mechanism.Pharmacokinetics: With 1 dose, the Cmax and AUC increased in an approximately dose proportional manner. The mean terminal half-life ranged between 6 – 7 days in the higher dose cohorts.Safety: Treatment with CNTO 528 was generally well tolerated. There were no serious adverse events (AEs) and few CNTO 528-related AEs. Two subjects in the highest dose cohort met the protocol pre-specified interruption rule of Hgb ≥ g/dL and underwent phlebotomy. In these subjects, high Hgb concentrations were not associated with AEs or clinical symptoms. All AEs were determined by the investigator to be mild to moderate in intensity. The most common AE across all groups was headache, occurring in both CNTO 528- and PBO-treated subjects. There was no dose-related trend across groups, and most subjects who experienced headaches were in the lowest 2 dose groups. There was no indication that any patterns of AEs or significant safety laboratory, vital signs, or ECG abnormalities were associated with the administration of CNTO 528.Immunogenicity: None of the 24 subjects who received single IV administration of CNTO 528 were positive for antibodies to CNTO 528.Conclusions: Single and fractionated IV administrations of CNTO 528 were well tolerated and resulted in prolonged, dose-dependent erythropoietic responses with notably low inter-subject variability. PK of IV CNTO 528 was linear and approximately dose proportional. No immunogenicity was observed. This data provides the first proof of concept in humans for erythropoietic responses and up-regulation of endogenous EPO levels by an erythropoietic mimetic antibody fusion protein.

Prevalence of iron deficiency and anemia among strenuously trained adolescents

Purpose There is a lack of awareness among physicians, dieticians, and public health planners as to the prevalence of iron deficiency and anemia among adolescents undergoing strenuous physical training. The aim of this study was to estimate the prevalence of iron deficiency and anemia among male adolescents undergoing such activity. Methods We studied 292 male adolescents on the day of entry into a volunteer military unit. Hemoglobin (Hb), mean corpuscular volume, ferritin, iron, iron-transferrin saturation, and soluble transferrin receptor (TfR) were measured, and TfR-F index was calculated. Results The mean Hb level (±SD) in the study population was 14.7 ± .9 g/dL (range, 10.8–16.8 g/dL), mean ferritin level was 50.6 ± 32.6 ng/mL (range, 5.4–162.5 ng/mL), and mean iron level was 97.1 ± 39.9 μg/dL (range, 24–267 μg/dL). The prevalence of anemia (Hb <14 g/dL) was 18.5%, and 3.4% had Hb concentrations less than 13 g/dL. Iron deficiency (ferritin <22 ng/mL) was present in 18% of the subjects, and 11.3% had ferritin levels less than 17 ng/mL. The mean soluble transferrin receptor concentration was 1.9 ± .8 mg/L, and the mean TfR-F index was 1.21 ± .57. Conclusions Nearly 19% of the study subjects had mild anemia at recruitment, and depletion of iron stores was observed among 18%. Overall, these changes were not accompanied by a significant increase in soluble TfR. This high prevalence is most likely the result of “sports anemia” due to the intense physical training regimen adopted prior to their recruitment.

Restless legs syndrome

To assess the prevalence and severity of restless legs syndrome (RLS) in the general community and to investigate its potential relationship with iron metabolism and other potential risk factors. This was a cross-sectional study of a sex- and age-stratified random sample of the general population (50 to 89 years; n = 701). The diagnosis of RLS was established by face-to-face interviews; severity was graded on the RLS severity scale. Each subject underwent a thorough clinical examination and extensive laboratory testing. The prevalence of RLS was 10.6% (14.2% in women, 6.6% in men); 33.8% of all patients with RLS had mild, 44.6% had moderate, and 21.6% had severe disease expression. None had been previously diagnosed or was on dopaminergic therapy. Free serum iron, transferrin, and ferritin concentrations were similar in subjects with and without RLS. However, soluble transferrin receptor (sTR) concentrations were different in subjects with and without RLS (1.48 vs 1.34 mg/L; p < 0.001). Female sex and high sTR independently predicted the risk of RLS. This large survey confirms the high prevalence, female preponderance, and underrecognition of restless legs syndrome in the general community. Although two-thirds of patients had moderate to severe disease, none was on current dopaminergic therapy.

Soluble transferrin receptor concentration is not superior to log ferritin for evaluating erythropoiesis in adolescents with iron deficiency anemia

Background This study investigated the associations of soluble transferrin receptor (sTfR), log ferritin, the ratio of sTfR to log ferritin (sTfR-F index), and the log of the ratio of sTfR to ferritin [log(sTfR/F)] vs. reticulocyte production during iron deficiency. Methods Fluorescent intensity of reticulocytes, immature reticulocyte fraction (IRF), reticulocyte maturity index (RMI), sTfR, and serum ferritin were measured in 149 adolescents. Results There were no significant differences in reticulocyte parameters between the iron deficiency anemia (IDA) subjects with sTfR≥4.9 mg/l and those with sTfR<4.9 mg/l. However, IDA subjects with log ferritin <0.73 μg/l exhibited significantly higher mean values for IRF and RMI, compared to those with log ferritin ≥0.73 μg/l (2.75±1.36% vs. 1.45±1.01%, p<0.05; 2.76±1.31% vs. 1.46±1.09%, p<0.05). In the non-IDA group, reticulocytes averaged 0.97±0.31% in subjects with sTfR≥2.1 mg/l, which were significantly above the values in those with sTfR<2.1 mg/l (0.72±0.16%, p=0.005), but no significant differences were observed in reticulocyte parameters between the subjects with log ferritin ≥1.35 μg/l and those with log ferritin <1.35 μg/l. Correlation coefficients of log ferritin vs. RMI ( r=−0.41) were higher than those of sTfR, sTfR-F index, and log(sTfR/F) vs. RMI ( r=0.24, r=0.30, and r=0.28, respectively) in IDA subjects. Conclusion Reticulocytopoiesis is more closely associated with log ferritin value than with sTfR concentrations in IDA patients, although sTfR significantly reflects erythropoietic activity in non-IDA subjects.

Effect of postpartum iron supplementation on red cell and iron parameters in non‐anaemic iron‐deficient women: a randomised placebo‐controlled study

To investigate the effect of oral iron on postpartum red cell and iron parameters in non-anaemic women with iron deficiency. Randomised study of supplementation with oral iron sulphate 80 mg daily or placebo for 12 weeks starting 24-48 hours after delivery, with visits antepartum and 1, 4, 6 and 12 weeks postpartum. Swiss university hospital obstetric unit. Fifty-two women with antenatal iron deficiency (serum ferritin <15 microg/L) and no antenatal or postnatal anaemia (haemoglobin >11 g/dL up to 48 hours before delivery, and >10 g/dL postpartum), divided into two groups comparable in antenatal iron status. Supplementation was started 24-48 hours after delivery (visit 1:V1). Additional tablets were issued one week after V1 (V2), four weeks after V1 (V3) and six weeks after V1 (V4). The last visit took place 12 weeks after visit 1 and 6 weeks after visit 4 (V5). Patients were required to return blisters and boxes whether they were used and unused at each visit and compliance was assessed by counting the tablets. Blood samples for haematology and iron status testing were taken before delivery and at each visit. Iron status (serum ferritin, hypochromic red cells, iron, transferrin saturation, soluble transferrin receptor concentration); erythropoiesis (standard parameters, including reticulocyte indices); and inflammatory response (serum neopterin, C-reactive protein, white cell count) in five-datapoint profiles. Increased ferritin (P= 0.0004) and transferrin saturation (P= 0.03), decreased soluble transferrin receptors (P= 0.02); increased haemoglobin (P= 0.02) and decreased hypochromic red cells (P= 0.04) compared with placebo at 12 weeks, with no differences in other red cell or reticulocyte parameters. There was a positive correlation between C-reactive protein and postpartum ferritin. No correlation was observed in the puerperium between C-reactive protein and hypochromic red cells or soluble transferrin receptors. Haemoglobin levels and iron stores in women with term gestational iron deficiency benefit significantly from iron supplementation compared with placebo, even in an industrialised population.

THE ANEMIA OF FAMILIAL MEDITERRANEAN FEVER DISEASE

The aim of this study was to evaluate the incidence of anemia detected in familial Mediterranean fever (FMF) and the effect of disease activity and colchicine therapy along with inteleukins to laboratory tests, including serum transferrin receptor (TfR), in the diagnosis of anemia seen in FMF in children. After detecting anemia in 63.4% of 172 FMF patients followed up by our rhematology outpatient polyclinics, it was decided to study 3 groups of patients: group 1, 17 newly diagnosed FMF patients; group 2, 36 FMF patients on colchicine therapy; and group 3, 17 healthy children as control for the symptom of anemia. All 3 groups of patients were investigated for their hematological parameters, iron status, including soluble transferrin receptor (sTFR) concentrations and sTFR index, and IL-6 levels. Anemia ratio was 9/17, 53%; 11/36, 31%; and 1/17, 5% in the groups 1, 2 and 3, respectively. There was a significant difference between hemoglobin (Hb) values in the first group and the second (patients who were on colchicine therapy). Furthermore, in the second group there was a significant difference between the Hb concentrations at the time of diagnosis and after colchicine therapy (p =. 003). There was a positive correlation between Hb and plasma iron and transferrin saturation in group 1 and disease beginning age, iron, transferrin saturation, and erythrocyte sedimentation rate (ESR) in the second group. In the first group the anemic patients' iron and transferrin saturation were significantly lower than normal, while ferritin levels were higher. In the second group, a good correlation was found with ESR and Hb levels; the higher ESR values were detected in patients with lower Hb values. Of the anemic and nonanemic patients of the first and second groups, values for interleukin 6 and iron parameters, including sTFR, were found similar. Anemia detected in FMF patients was found related to iron status more than interleukins. Colchicine therapy had a positive effect on anemia as well as on disease activity. Resolution of symptoms of FMF occurred with correction of the anemia, if the patient ESR values also decreased on colchicine therapy.

Folate Deficiency Does Not Alter the Usefulness of the Serum Transferrin Receptor Concentration as an Index for the Detection of Iron Deficiency in Mexican Women during Early Lactation

The purpose of this study was to investigate the usefulness of soluble serum transferrin receptor (TfR) concentration, TfR index and log TfR:ferritin ratio (TfR outcomes) in detecting tissue Fe deficiency among breast-feeding Otomi women residing in Capulhuac, Mexico (2800 m above sea level) and to determine whether folate deficiency modifies the interpretation of these data. Lactating women (n = 68) provided blood samples at 22 +/- 13 d (mean +/- SD) postpartum. Using the 3-index Fe assessment model with and without Hb, 2 women (3%) had Fe-deficient erythropoiesis, 24 (36%) Fe deficiency anemia, and 19 (29%) indeterminate Fe status; 29 (43%) and 5 (7.5%) women had plasma and erythrocyte folate concentrations below normative cutoff values, respectively. Mean values for TfR outcomes were higher among women classified as Fe deficient than those who were Fe sufficient, but did not differ with low or normal blood folate concentrations. Similarly, TfR outcomes did not differ among women with normocytic or macrocytic erythrocytes. Receiver-operating characteristic (ROC) curves generated for TfR outcomes yielded areas under the curve from 0.62 to 0.68, indicating that each of these measures, on its own, is a poor predictor of tissue Fe deficiency in lactating women. In conclusion, low blood folate concentrations or the presence of macrocytosis in Otomi women from Capulhuac, Mexico (moderate altitude) did not influence the utility of TfR outcomes for the detection of Fe deficiency during early lactation. Further, on their own, TfR, TfR index, and TfR:ferritin ratio were poor predictors of tissue Fe deficiency for any given individual.

Determination of iron absorption from intrinsically labeled microencapsulated ferrous fumarate (sprinkles) in infants with different iron and hematologic status by using a dual-stable-isotope method

The use of microencapsulated ferrous fumarate sprinkles is a new approach for home fortification. Iron and hematologic status may affect the absorption of iron from sprinkles. The objective was to measure the absorption (corrected erythrocyte incorporation of (57)Fe) of 2 different doses of iron from sprinkles added to a maize-based complementary food provided to infants with different iron and hematologic status. Infants aged 6-18 mo were randomly assigned to receive either 30 (n = 45) or 45 (n = 45) mg elemental Fe as (57)Fe-labeled sprinkles added to a maize-based porridge on 3 consecutive days. A (58)Fe tracer (0.2 mg as ferrous citrate) was also infused intravenously (n = 46). Blood was drawn at baseline and 14 d later to determine erythrocyte incorporation of (57)Fe and (58)Fe by using inductively coupled plasma mass spectrometry. On the basis of hemoglobin and soluble transferrin receptor concentrations, subjects were classified as having iron deficiency anemia (IDA), iron deficiency (ID), or sufficient iron status. There was no significant effect of dose on iron absorption (P > 0.05). Geometric mean iron absorption was 8.25% (range: 2.9-17.8%) in infants with IDA (n = 32), 4.48% (range: 1.1-10.6%) in infants with ID (n = 20), and 4.65% (range: 1.5-12.3%) in iron-sufficient infants (n = 20). Geometric mean iron absorption was significantly higher in infants with IDA than in infants with ID or iron-sufficient infants (P = 0.0004); however, there were no significant differences between infants with ID and iron-sufficient infants. During infancy, iron absorption from sprinkles in a maize-based porridge meets and surpasses requirements for absorbed iron and is up-regulated in infants with IDA.

The effects of physical exercise on the concentrations of ferritin and transferrin receptor in plasma of male judoists.

The aim of the study was to assess the within-subject (day-to-day) variability for iron status variables: ferritin (ferr) and soluble transferrin receptor (sTfR) concentrations in plasma and the sTfR/log ferr index in athletes subjected daily to high physical loads. Blood was sampled in the morning from 8 healthy male elite judoists, aged 20 - 31 years, for 10 consecutive days while at training camp. Mean concentrations of ferritin and sTfR in plasma for the 10 day period were 32.0. 1.771(+/-1) and 2.41. 1.324(+/-1) mg/l, respectively. The average within-subject, day-to-day variability for ferritin was 27.4 % (range: 16 - 44 %), and was much lower for sTfR (6.7 %; range: 4 - 15 %). Ferritin concentrations were significantly, albeit weakly, correlated with training loads on the preceding day (r = 0.256; p < 0.05) and with creatine kinase (CK) activities on the same day (r = 0.397; p < 0.001), while sTfR did not correlate with either training loads or CK activities. Mean day-to-day variability for the sTfR/log ferr index was 11.8 % (range: 5 - 21 %), i.e. markedly lower than for ferritin. Although the physical load-induced changes in iron metabolism indices in male subjects were similarly oriented as in the earlier reported female ones representing the same sport, the magnitude of those changes was less pronounced than in the females. This was evidenced by a markedly lower within-subject day-to-day variability in ferritin, still significant but weak correlation between load magnitude and ferritin levels, and a significant, negative correlation between ferritin and sTfR concentrations, not found previously in the female athletes. However, despite lower variability in ferritin than in women, the exercise-induced ferritin increases in male athletes might make a reliable assessment of iron stores in them difficult. The present results confirm our earlier reports that sTfR levels are stable under high physical loads, thus making them a useful indicator of iron status. Also sTfR/log ferr index is of a much higher diagnostic value than ferritin, despite high variability of the latter. That index is particularly valuable in detecting iron-deficient erythropoiesis.

Value of serum ferritin and soluble transferrin receptor for prediction of coronary artery disease and its clinical presentations

We investigated whether there is an association between serum ferritin or soluble transferrin receptor (sTfR) concentrations and coronary artery disease (CAD) or its clinical presentations. This is a case–control study that included 892 patients (664 cases with angiographically proven CAD and 228 controls without CAD). Blood was collected before angiography for determination of sTfR, ferritin and C-reactive protein (CRP). The values (median, 25th–75th percentiles) of sTfR (2.6 [2.1; 3.2] mg/l versus 2.4 [2.1; 3.0] mg/l, P=0.13) or ferritin (140.1 [74.8; 248.3] ng/ml versus 120.1 [74.9; 218.0] ng/ml, P=0.11) did not differ significantly between cases or controls. The values of sTfR in the case subjects with 1-vessel, 2-vessel, and 3-vessel CAD were: 2.4 [2.0; 3.0], 2.6 [2.0; 3.2], and 2.8 [2.2; 3.3] mg/l, respectively ( P=0.003). In multivariate analysis, neither sTfR ( χ 2=0.14, P=0.70) nor ferritin ( χ 2=2.8, P=0.09) correlated independently with the presence of CAD. In case subjects with stable angina, unstable angina, and acute myocardial infarction (MI), ferritin concentrations were: 127.5 [69.5; 214.0], 138.9 [86.1; 278.0], and 175.0 [93.5; 314.5] ng/ml, respectively ( P<0.001). Our results showed that serum concentrations of sTfR or ferritin do not predict the risk for coronary artery disease. In subjects with pre-existing CAD, those with more severe disease had increased levels of sTfR. Patients with CAD presenting with acute coronary syndromes showed increased levels of serum ferritin.