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

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.

Longer survival associated with HLA‐A*03, B*14 among 212 hemochromatosis probands with HFE C282Y homozygosity and HLA‐A and ‐B typing and haplotyping1

“…It has been postulated that there is a regulatory element in the vicinity of HFE that influences both CD8 + T‐lymphocyte numbers and iron overload phenotypes in an inverse manner (39–41). In hemochromatosis probands with C282Y homozygosity, presence of the HLA‐B*14 allele was associated with significantly higher total blood lymphocyte counts, whereas positivity for either HLA‐A*01 or the ‐B*08 allele was associated with significantly lower total blood lymphocyte counts (40).…”

Total blood lymphocyte counts in hemochromatosis probands with HFEC282Y homozygosity: relationship to severity of iron overload and HLA-A and -B alleles and haplotypes

“…Further, hepcidin levels are significantly decreased in persons who have hemochromatosis associated with mutations of HFE (Ch6p21.3) [32]. Although most reports of lymphocyte numbers and subsets have been made in persons presumed or documented to have HLA- or HFE -associated hemochromatosis or iron overload, lymphopenia also occurred in an unusual case of early age-of-onset hemochromatosis and severe iron overload associated with homozygosity for a hepcidin promoter mutation on Ch19q13 [33]. …”

A Portuguese patient homozygous for the -25G>A mutation of the HAMP promoter shows evidence of steady-state transcription but fails to up-regulate hepcidin levels by iron

“…6 Here, the same mutation was found in a different Portuguese family where the proband shows coincidental association of JH, Turner syndrome, and absolute lymphopenia. 7 Although no comparative haplotype analysis was performed, geographic and historical tracking does not indicate any relationship with the previously described family. In the proband, no mutations in the coding regions of HAMP and hemojuvelin genes were found by sequencing.…”