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

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

The study was supported by Grant Nos. PI16/01335 and PI19/00451 (to A.L.-B.) and PI17/00557 (to J.B.) from the National Institute of Health Carlos III (Fund for Health Research FIS, Spain), projects co-financed by Fondo Europeo de Desarrollo Regional (FEDER). GC-B holds a Sara Borrell fellowship from the National Institute of Health Carlos III (CD19-00172)