Are children with growth hormone deficiency more susceptible to pneumococcal disease?
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Pr Vincent Geenen's Immunoendocrinology Laboratory at GIGA-I3 has just obtained important results 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 and Frontiers in Immunology.
The researchers wanted to observe the effects of GH deficiency on immune system function from mice whose genes coding for hypothalamic GH releasing factor (GHRH) have been invalidated. These mice designated GHRH-KO have severe growth deficiency and weigh about 60% less than wild mice (FIG1A).
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, 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 48-72 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 Vincent Geenen, "these unambiguous results have a direct consequence: it will be important to monitor spleen development and response to pneumococcal vaccines in children with GH deficiency, especially of 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).
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
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
Figure 1 – Main observations collected from GHRH-KO (KO), wild (WT) and heterozygous (HZ) mice
A. Dwarfism of a KO mouse compared to a WT mouse following growth hormone (GH) deficiency.
B. Atrophy of the spleen of a KO mouse (right) compared to a WT mouse.
C. Unlike WT and HZ mice, KO mice develop pneumococcal sepsis as early as 24 hours after infection (P.I.) by intra-nasal instillation of a non-fatal dose of pneumococci.
D. Normal aspect of the lung of a WT mouse infected with a non-fatal dose of pneumococci.
E. Massive inflammatory infiltration into the lung of a KO mouse infected with a non-fatal dose of pneumococci.
Note: HZ mice do not have GH deficiency.
These studies were supported by the Government of Lebanon, FRIA, FNRS, Fondation Léon Fredericq and Wallonia-Brussels Federation (CRA Somasthym).