Changes in Growth Hormone Receptor Gene Expression during Therapy in Children with Juvenile Idiopathic Arthritis

Abstract

Background: High levels of cytokines in juvenile idiopathic arthritis (JIA) can alter target cell sensitivity to growth hormone (GH) leading to short stature in adulthood. We hypothesized that the down-regulation of GH receptor (GHR) gene expression could be involved in growth failure of children with JIA. Methods: In 18 (12 F and 6 M) prepubertal JIA patients and 13 age- and sex-matched healthy children, we evaluated serum growth-promoting factors and inflammatory indexes. We also measured GHR gene expression, by real-time PCR, in lymphocytes of patients and controls. All parameters were evaluated in patients before and after treatment of JIA. Results: The most interesting (p = 0.007) result was the increase in GHR mRNA expression in all JIA patients. Moreover, we observed a significant (p = 0.0156) decrease in IL-6 levels in JIA patients after 2 years of therapy (19.37 ± 41.01) with respect to basal values (90.84 ± 124.71). On the contrary, IGF-I significantly (p = 0.0005) increased to a mean SDS value of 0 (range -1.69 to +1.70 SDS) with respect to values at disease onset (-0.64 SDS). Conclusions: Our preliminary data suggest that the restoration of both GHR gene expression and IGF-I secretion correlate with inactive disease in JIA children.

Effects of growth hormone therapeutic supplementation on hematopoietic stem/progenitor cells in children with growth hormone deficiency: focus on proliferation and differentiation capabilities

“…As GHR expression is a key target that influences the effectiveness of GH, the analysis of its expression in HPCs is invaluable. The expression of GHR at the mRNA and protein levels was previously detected in human mature T and B lymphocytes and monocytes/macrophages [ 23 , 24 ]. However, there is a lack of studies providing the evidence that GHR is expressed in CD34 + -enriched HPCs from PB of GHD children.…”

Inflammatory Diseases and Growth: Effects on the GH–IGF Axis and on Growth Plate

“…GHR mRNA expression has been reported to be significantly reduced in mononuclear cells of JIA patients at the onset of the disease, with a restoration of GHR expression after two years of treatment [ 163 ]. However, these data remain controversial, as other authors did not report changes in GHR gene expression in a rat experimental arthritis model [ 164 ].…”

Longitudinal Growth in Rheumatologic Conditions: Current and Emerging Treatments of Growth Delay in Children with Chronic Autoimmune Diseases

“…Growth delay in generalized linear growth occurs predominantly in the systemic onset juvenile arthritis population and to a lesser degree in those with poly-articular onset JIA associated with RF positivity [32]. During active disease in JIA, elevated serum levels of cytokines may modify target cell's sensitivity by down-regulating the GH receptor (GHR) gene expression, leading to short stature as an adult [33]. Therefore, the shortcoming of GH function during JIA is explained more as resistance to growth hormones than deficiency in growth hormone secretion.…”