Low serum transferrin levels in HFE C282Y homozygous subjects are associated with low CD8+ T lymphocyte numbers

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. D

Mechanisms of plasma non‐transferrin bound iron generation: insights from comparing transfused diamond blackfan anaemia with sickle cell and thalassaemia patients

“…It would be of interest to determine whether aplastic anaemia patients show the same high NTBI in relation to low sTfR as in DBA. The decreased transferrin levels in all disease groups, parallels findings in hereditary haemochromatosis (Macedo et al , ). This may exacerbate NTBI levels where a primary mechanism for NTBI generation already exists.…”

Ferritin and ferrihydrite nanoparticles as iron sources for Pseudomonas aeruginosa

“…Moreover, under normal conditions, ferritin is present in low concentrations in the extracellular milieu. Plasma concentrations of ferritin are only 1.5–30 ng/ ml, compared with 200–320 µg/ml for transferrin [8, 9]. …”

Outcome of liver transplantation in hereditary hemochromatosis

“…Macedo et al. [22] reported low CD8 lymphocyte numbers and low serum transferrin levels associated with a more severe expression of iron overload in HH patients. From our limited data it appeared that infectious complications were more common in patients who did not have venesection therapy before LT.…”

“…These include an abnormal CD4:CD8 ratio, decreased cutaneous hypersensitivity and abnormal proliferative responses by peripheral blood mononuclear cells to mitogenic stimuli [13,21]. Macedo et al [22] reported low CD8 lymphocyte numbers and low serum transferrin levels associated with a more severe expression of iron overload in HH patients. From our limited data it appeared that infectious complications were more common in patients who did not have venesection therapy before LT.…”