Boys with Early JIA Have Greater Deficit of IGF-1 than Girls, Study Shows

Boys with Early JIA Have Greater Deficit of IGF-1 than Girls, Study Shows

Boys with early juvenile idiopathic arthritis (JIA) have lower levels of insulin-like growth factor 1, a growth hormone, compared to age-matched girls in the same stage of early disease, a study reports.

The study, “Low serum IGF-1 In Boys with Recent Onset of Juvenile Idiopathic Arthritis,” was published in the Journal of Immunology Research.

The onset of JIA, the most common rheumatic disease in children, occurs before age 16. While the mechanisms of the disease remain unknown, it is thought to involve environmental triggers and specific immune system factors.

A common feature of children with JIA is slower-than-normal growth, resulting in a shorter final height; the cause of this is unknown.  Contributing factors include increased levels of pro-inflammatory molecules (cytokines), delayed puberty onset, malnutrition, and long-term glucocorticoid therapy.

Previous studies have shown that levels of insulin-like growth factor 1 (IGF-1) are lower in JIA children than in healthy ones. IGF-1 is a well-established growth hormone and is the main regulator of linear growth in children. But the question of the levels of IGF-1 and its variations between boys and girls with JIA, and IGF-1 levels differing in early disease compared to established JIA, needed to be studied.

In the study, researchers compared the levels of circulating IGF-1 in boys and girls who were newly diagnosed with JIA, in those with established JIA and in healthy age- and sex- matched controls.

A total of 131 Estonian children (mean age 10.2 years) diagnosed with JIA were recruited. Forty-three percent were boys. Half the children had early disease (27 boys and 38 girls, defined as less than one month from being diagnosed) and the other half were classified as established JIA patients (29 boys and 37 girls, mean disease duration 17.9 months). There were 47 children age- and sex-matched for healthy controls.

Most children with early JIA did not take steroids (92 percent) or disease-modifying antirheumatic drugs (DMARDs, 85 percent). In the established JIA group, 87 percent of boys and 63 percent of girls received DMARDs.

Blood analysis showed that the levels of IGF-1 were significantly lower in early JIA patients compared with control groups, and no differences were found for the established JIA group.

IGF-1 levels in boys with early JIA were 12 times lower than those of girls with early JIA. No sex-related differences were detected among controls or patients with established JIA.

Researchers examined how IGF-1 levels were related to age in the different subgroups. Age correlated strongly to blood IGF-1 among healthy male controls (older boys had higher IGF-1 levels), but not in boys with early JIA.

IGF-1 levels also correlated strongly to age in healthy female controls. However, in contrast to the boys, there was a more moderate correlation between age and IGF-1 in girls with early JIA.

In established JIA, there was a strong correlation between age and serum IGF-1 levels in both sexes.

While there were no significant height differences, regardless of sex, boys with established JIA tended to be shorter. Height correlated strongly to blood levels of IGF-1 in male controls, but not in those with early JIA.

In girls, height correlated to blood IGF-1 levels in both healthy controls and in those with early JIA.  In established JIA, there was a significant correlation between height and serum IGF-1 levels.

While high blood IGF-1 levels had a positive correlation with inflammation markers (such as C-reactive protein) in boys with early JIA, this was not seen in girls.

The researchers believe that because IGF-1 levels positively correlate to age in pre-puberty, and as boys usually begin puberty later than girls, this could explain the lower levels of IGF-1 for boys with early JIA.

Overall, these findings show “a sex-dependent deficiency in serum IGF-1 in boys with early JIA, which argues for sex-related differences in biological mechanisms involved in the disease pathogenesis [the way a disease develops],” they said.

Based on our results, there is a need for further investigation of sex-based differences in biological mechanisms involved in the very early phase of JIA process in larger cohorts.”