Browsing by Author "CRUZ, E."
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- Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overloadPublication . Porto, Graça; CARDOSO, C.S.; GORDEUK, V.; CRUZ, E.; FRAGA, J.; AREIAS, J.; OLIVEIRA, J.C.; BRAVO, F.; GANGAIDZO, I.T.; MACPHAIL, A.P.; GOMO, Z.A.; MOYO, V.M.; MELO, G.; SILVA, C.; JUSTICA, B.; DE SOUSA, M.Eur J Haematol. 2001 Aug;67(2):110-8. Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload. Porto G, Cardoso CS, Gordeuk V, Cruz E, Fraga J, Areias J, Oliveira JC, Bravo F, Gangaidzo IT, MacPhail AP, Gomo ZA, Moyo VM, Melo G, Silva C, Justiça B, de Sousa M. Haematology, Santo António General Hospital, Porto, Portugal. gporto@ibmc.up.pt Abstract To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, total lymphocyte counts and iron status were also examined in 20 index patients with African dietary iron overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher iron stores than in those without cirrhosis and with lower iron burdens [(1.65 +/- 0.43) x 10(6)/mL vs. (2.27 +/- 0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with iron overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with iron overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African iron overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree of iron loading in HFE haemochromatosis but not in African iron overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.
- Growth hormone (GH)‐induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome.Publication . PORTO, G.; CRUZ, E.; MIRANDA, H.; PORTO, B.; VASCONCELOS, J.; LACERDA, R.; ROETTO, A.; DARAIO, F.; BACELAR, C.Clin Endocrinol (Oxf). 2004 Oct;61(4):437-40. Growth hormone (GH)-induced reconstitution of CD8+ CD28+ T lymphocytes in a rare case of severe lymphopenia associated with Juvenile Haemochromatosis and Turner's syndrome. Porto G, Cruz E, Miranda HP, Porto B, Vasconcelos JC, Lacerda R, Roetto A, Daraio F, Bacelar C. Santo António General Hospital, Porto, Portugal. gporto@ibmc.up.pt Abstract This paper describes a rare case of Turner's syndrome associated with Juvenile Haemochromatosis and severe lymphopenia, followed-up for a period of 5 years. Because of the indication for treatment with growth hormone (GH), this case was observed as a model to analyse the effects of GH on growth, iron mobilization and lymphocyte reconstitution. For this purpose, a serial study of the T lymphocyte subpopulations CD4+, CD8+, CD8+ CD28+ and CD8+ CD28- was performed by immunophenotyping during the follow-up period. Besides the impact of both phlebotomy treatment and GH on the rapid growth and mobilization of 20.8 g of iron in 136 weeks, the most relevant observation was the finding of a significant expansion of CD8+ T lymphocytes expressing the costimulatory marker CD28 in the setting of the severe lymphopenia. These findings constitute new clinical evidence supporting the notion that the GH/IGF-1 system has an important role on the maintenance of T cell homeostasis in vivo, and that GH may be regarded as a putative therapeutic agent in T lymphocyte reconstitution. PMID: 15473875 [PubMed - indexed for MEDLINE]
- Low serum transferrin levels in HFE C282Y homozygous subjects are associated with low CD8(+) T lymphocyte numbers.Publication . MACEDO, M.F.; CRUZ, E.; LACERDA, R.; PORTO, G.; DE SOUSA, M.Blood Cells Mol Dis. 2005 Nov-Dec;35(3):319-25. Epub 2005 Sep 1. Low serum transferrin levels in HFE C282Y homozygous subjects are associated with low CD8(+) T lymphocyte numbers. Macedo MF, Cruz E, Lacerda R, Porto G, de Sousa M. SourceDivision of Human Genetics and Genetic Disorders, Iron Genes and the Immune System Laboratory, Institute for Molecular and Cell Biology (IBMC), Oporto, Portugal. Abstract Hereditary hemochromatosis (HH) is a genetic iron overload disease, in the majority of cases associated with homozygosity for the C282Y mutation of the HFE gene. In spite of this genetic homogeneity, there is a great clinical heterogeneity among HH patients. Low CD8(+) lymphocyte numbers have been associated with a more severe expression of iron overload in HH patients, and in experimental models of iron overload. HH patients present low serum transferrin levels. Transferrin is an indispensable resource for lymphopoiesis. Lymphocyte homeostasis follows general ecology rules of population dynamics that involve competition for limiting resources. In the present study, we questioned whether transferrin levels could be associated with the anomalies seen previously in lymphocyte subset numbers in HH patients. Transferrin levels, total and subset T lymphocyte counts were done in 426 apparently healthy subjects genotyped for HFE. All HFE C282Y carriers presented significantly lower serum transferrin levels than the wild type group, a difference that could not be explained solely by the degree of iron overload. Significant differences were also seen in transferrin levels between males and females, with females presenting higher average serum Transferrin levels. In the population of subjects with Transferrin levels lower than 248 mg/dl, a positive correlation was seen between the peripheral CD8(+) lymphocyte numbers and serum transferrin levels (R(2) = 2.41; r = 0.16; P = 0.018). To test the possible limiting resource effect of transferrin, the correlation between transferrin levels and CD8(+) lymphocyte numbers was scrutinized in 34 HH patients, homozygous for the C282Y mutation. In the homozygous males, where the lowest average transferrin levels were seen, another highly significant correlation was observed between Transferrin levels and CD8(+) numbers. This correlation points to a possible role of transferrin as a limiting resource for MHC class I dependent lymphocyte proliferation, an effect that was not observed in C282Y homozygous female patients. PMID: 16140024 [PubMed - indexed for MEDLINE]