IMMUNOGLOBULIN G GLYCOSYLATION IN DOWN SYNDROME

Abstract

Glikozilacija je jedna od najčešćih ko- i posttranslacijskih modifikacija proteina. Glikani vezani na imunoglobulin G (IgG) utječu na njegovu strukturu i funkciju i mijenjaju se s dobi te u brojnim fiziološkim i patološkim stanjima organizma. Znakovi preuranjenog starenja, kao i brojne druge bolesti, česti su kod Downova sindroma (DS). Tekućinskom kromatografijom ultravisoke učinkovitosti analizirana je glikozilacija IgG-a u tri populacije osoba s DS-om za koje su postojali klinički podaci o najčešćim komorbiditetima i uspoređena s onom njihovih zdravih vršnjaka. Proučen je utjecaj produkata gena kromosoma 21 B3GALT5, RUNX1 i DYRK1A na glikozilaciju IgG-a u DS-u digestijom glikana IgG-a egzoglikozidazama te kemijskom inhibicijom produkata gena u limfoblastoidnim staničnim linijama. Pokazano je kako glikozilacija IgG-a osoba s DS-om neovisno o učestalim komorbiditetima odgovara kronološki starijim zdravim osobama. U korištenim eksperimentalnim sustavima RUNX1 ima izravan utjecaj na glikozilaciju IgG-a u DS-u, dok B3GALT5 i DYRK1A nemaju.Glycosylation is one of the most common co- and posttranslational modifications. Glycans attached to immunoglobulin G (IgG) affect its function and change with age and in numerous physiological and pathological conditions. Signs of premature aging, along with many other diseases, are common in Down syndrome (DS). IgG glycosylation of three DS populations that had clinical data on the most common comorbidities was analyzed by ultra-high performance liquid chromatography and compared to their healthy peers. The impact of chromosome 21 gene products B3GALT5, DYRK1A and RUNX1 on IgG glycosylation was studied using enzymatic digestions of IgG glycans and IgG-producing lymphoblastoid cell lines obtained from individuals with and without DS. IgG glycosylation was revealed to be significantly shifted in the direction of aging in DS, showing a ubiquitous trend independent of comorbidities, and an insight into the effect of gene products B3GALT5, DYRK1A and RUNX1 on IgG glycosylation was provided