Longitudinal association of the anti-inflammatory serum marker GDF-15 with serum IgA and IgG in apparently healthy children

Gemma Carreras-Badosa,Francis De Zegher,Ariadna Gómez-Vilarrubla,Anna Prats-Puig,Abel López-Bermejo,Lourdes Ibáñez,Berta Mas-Parés,Elsa Puerto-Carranza,Judit Bassols,Silvia Xargay-Torrent

doi:10.1038/s41598-021-97386-1

Abstract

Both the innate and adaptive immune responses are deregulated in individuals with obesity and are key drivers of its associated metabolic alterations. Although the anti-inflammatory growth differentiation factor 15 (GDF-15) is a candidate protein against obesity, its mechanisms regulating the immune responses are not fully cleared. We examined whether GDF-15 was related to serum immunoglobulins in a children’s cohort assessed longitudinally during childhood. Results showed that circulating GDF-15 positively associated with IgA (p < 0.002) and IgG (p < 0.001) levels and the IgA*IgG product (p < 0.001) in apparently healthy children at both baseline (age 9) and follow-up (age 13). The associations were readily observed in heavier children (those with BMI-SDS above the median) as well as in children with higher renal fat accumulation (those with renal fat-to-height ratio above the median) and remained significant after correcting for possible confounding variables. Serum GDF-15 levels accounted for up to 16% of the variance of follow-up IgG levels and up to 14% of the variance of follow-up IgA*IgG product. The longitudinal associations of the anti-inflammatory GDF-15 with IgA, IgG and the IgA*IgG product in children with higher BMI or higher renal fat accumulation suggest a role of GDF-15 in human obesity through the regulation of the immune adaptive system.

Highlights

Obesity and its associated metabolic alterations have reached epidemic proportions, in c hildhood[1]
Differences between subgroups according to renal fat-to-height ratio were seen in almost all anthropometric parameters being analyzed such as weight, height, body mass index (BMI) and renal fat (Table 1)
When analyzing the subgroups defined by the median of BMI-standard deviation scores (SDS) or the median of renal fat-to-height ratio, children with higher BMI-SDS and especially those with higher renal fat-to-height showed positive correlations between circulating growth differentiation factor 15 (GDF-15) and IgA (p = 0.004), IgG (p = 0.001) levels and the IgA*IgG product (p < 0.001; Fig. 1a)

Summary

Introduction

Obesity and its associated metabolic alterations have reached epidemic proportions, in c hildhood[1]. Despite the fact that GDF-15 is recognized as a key circulating antiinflammatory factor, scarce publications in obese children have been r eported[5] and its mechanisms regulating immune responses are not fully elucidated. IgA and IgG have been related to a poorer metabolic profile in obese children[6], and. Higher concentrations of IgA and IgG have been reported in obese adults[7] and children[8], suggesting that there is a relationship between the adaptive immune system and adipose tissue function. We hypothesized that GDF-15 would be associated with components of the immune system in children with obesity. The aim of this study was to examine whether GDF-15 was related to serum levels of IgA and IgG in a cohort of apparently healthy children assessed longitudinally during childhood both at baseline and at follow-up. Analyses were performed in groups thereof with higher body mass index (BMI) or renal fat

Objectives

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Results

Conclusion