Are children with growth hormone (GH) deficiency more susceptible to pneumococcal disease?

Growth hormone deficiency – pneumococcal disease

GIGA-I³ Immunoendocrinology Laboratory (ULiège) recently delivered compelling results from fundamental research on mouse models.

Vincent Geenen’s Immunoendocrinology Laboratory at GIGA-I³ has obtained important data that could have an impact on the monitoring of children with growth hormone (GH) deficiency. These results have just been published in two successive publications, Frontiers in Endocrinology(1) and Frontiers in Immunology(2).

The researchers wanted to observe the effects of GH deficiency on immune functions from mice whose genes coding for hypothalamic GH releasing hormone (GHRH) have been invalidated (3). These mice designated GHRH-KO have severe growth deficiency and weigh about 60% less than wild mice (Fig. 1A). They were also shown to be resistant to the development of experimental autoimmune encephalomyelitis (4).

First, Gwennaëlle Bodart established that these GHRH-KO mice had severe spleen atrophy (Fig. 1B) as well as a decrease in B lymphocytes in the blood. Then, Khalil Farhat, a doctoral researcher at GIGA-I³, showed that GHRH-KO mice not only do not respond to pneumococcal vaccines but are dramatically susceptible to a non-fatal infection by pneumococcus, a thymo-independent pathogen.

Indeed, GHRH-KO mice die within 24-72 hours in a state of sepsis while wild mice normally eliminate this infection within 24 hours (Fig. 1C). The lung of infected WT mice confirms the absence of any lesion (Fig. 1D) while the lung of infected KO mice is massively infiltrated by inflammatory cells (Fig. 1E).

Khalil Farhat also identified alterations in the spleen cells of these KO mice that may partly explain this sudden and totally unexpected susceptibility to pneumococcus. Finally, there was no significant difference between WT mice and GHRH-KO mice exposed to a thymo-dependent pathogen, the influenza influenza virus.

For the authors, “These data further evidence the role of brain hypothalamus in the control of major immune responses. Furthermore, this dramatic and unexpected phenotype has a direct consequence: it will be important to monitor spleen development and response to pneumococcal vaccines in children with isolated GH deficiency, especially from congenital or genetic origin.”

In this translational research perspective, contacts have already been established with the Pediatric Endocrinology Department of the University Hospital of Liège (Pr Anne-Simone Parent) and BESPEED (Belgian Society of Pediatric Endocrinology).

Acknowledgments

These studies were supported by the Government of Lebanon, FRIA and FNRS (Belgium), Fondation Léon Fredericq and Wallonia-Brussels Federation (CRA Somasthym).

Authors Affiliations

Farhat, G. Bodart, H. Martens, Salvatori R* & Geenen V – University of Liège, GIGA-I3 Immunoendocrinology, B-4000 Liège-Sart Tilman, Belgium ; *Johns Hopkins University Medical Center, Division of Endocrinology & Metabolism, Baltimore, USA

References

(1) Bodart G, Farhat K, Renard- Charlet C, Becker G, Plenevaux A, Salvatori R, Geenen V and Martens H (2018), The Severe Deficiency of the Somatotrope GH-Releasing Hormone/Growth Hormone/ Insulin-Like Growth Factor 1 Axis of Ghrh^−/− Mice Is Associated With an Important Splenic Atrophy and Relative B Lymphopenia. Front. Endocrinol. 9:296. doi: 10.3389/fendo.2018.00296

(2) Farhat K, Bodart G, Charlet-Renard C, Desmet CJ, Moutschen M, Beguin Y, Baron F, Melin P, Quatresooz P, Parent A-S, Desmecht D, Sirard J-C, Salvatori R, Martens H and Geenen VG (2018) Growth Hormone (GH) Deficient Mice With GHRH Gene Ablation Are Severely Deficient in Vaccine and Immune Responses Against Streptococcus pneumoniae. Front. Immunol. 9:2175. doi: 10.3389/fimmu.2018.02175

(3) Alba M, Salvatori R (2004) A Mouse With Targeted Ablation of The Growth Hormone-Releasing Hormone Gene: A New Model Of Isolated Growth Hormone Deficiency. Endocrinology 145:4134-43. doi: 10.1210/en.2004.00296.

(4) Shohreh R, Pardo CA, Guaraldi F, Schally AV, Salvatori R (2011) GH, But Not GHRH, Plays A Role In The Development Of Experimental Autoimmune Encephalomyelitis. Endocrinology 152:3803-10. doi: 10.1210/en.2011-1317.

Contact

Vincent Geenen, MD, PhD; University of Liège GIGA Institute, GIGA-I³ Immunoendocrinology, CHU-B34, B-4000 Liège-Sart Tilman, Belgium; vgeenen@uliege.be Mobile : +32 477 46 90 95

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