| Abstract | Šećerna bolest tipa 1 (T1DM) multifaktorska je, kronična i autoimuna bolest koja nastaje kao posljedica nedostatka
endogenog lučenja inzulina iz β-stanica gušterače. Trenutno su dostupna dva biomarkera koji ukazuju na dugoročnu
kontrolu dijabetesa – HbA1c i fruktozamin, ali oba imaju svoja ograničenja. Stoga, postoji velika potreba za markerom
koji bi na precizniji način omogućio longitudinalno praćenje T1DM.
Promjene u profilu N-glikozilacije ukupnih proteina plazme i imunoglobulina G u mnogim su se studijama pokazale kao
potencijalni prognostički, dijagnostički i terapijski markeri raznih bolesti, posebice onih upalne prirode kao što je T1DM.
Glikozilacija imunoglobulina A u različitim bolestima općenito je manje proučavana, a tek prije nekoliko godina
započela su intenzivna istraživanja uloge njegove glikozilacije u T1DM.
Cilj ovog istraživanja je identificirati promjene u IgA N-glikozilaciji u populaciji odraslih bolesnika s T1DM te ih
usporediti sa zdravim osobama. Analiza glikana učinjena je HILIC-UPLC metodom. U ovom diplomskom radu je
otkriveno da kod odraslih ispitanika s dijagnosticiranim T1DM postoji statistički značajna promjena udjela glikanskih
struktura GP2, GP4, GP5, GP7, GP13, GP14, GP17, GP19, GP21, GP24, GP25, GP27 i GP29. Detaljnije proučavanje
deriviranih svojstava pokazalo je smanjenje udjela nisko razgranatih glikana, a povećanje visoko razgranatih glikana.
Nadalje, smanjenje udjela digalaktoziliranih glikana i povećanje udjela trigalaktoziliranih i trisijaliniziranih glikana
pronađeno je u bolesnika s T1DM. Udio glikana sa sržnom fukozom značajno je smanjen u bolesnika s T1DM, dok je
udio oligomanoznih glikana značajno povećan.
Ove promjene u glikozilaciji IgA upućuju na njegovu moguću ulogu u progresiji bolesti te na potrebu daljnjeg ispitivanja
njegove prognostičke vrijednosti. |
| Abstract (english) | Type 1 diabetes mellitus (T1DM) is a multifactorial, chronic, and autoimmune disease that results from a lack of
endogenous insulin secretion from pancreatic β-cells. There are two markers currently available that indicate long-term
diabetes control – HbA1c and fructosamine, but both have their limitations. Therefore, there is a great need for a marker
that would show the longitudinal progression of T1DM in a more precise way.
Changes in the N-glycosylation profile of total plasma proteins and immunoglobulin G in many studies have proven to
be a potential prognostic, diagnostic and therapeutic marker of various diseases, especially those of an inflammatory
nature, such as T1DM. Glycosylation of immunoglobulin A in various diseases has generally been less studied, and only
a few years ago, intensive research into the role of its glycosylation in T1DM began.
The aim of this study is to identify changes in IgA N-glycosylation in the population of adult patients with T1DM and
compare them with healthy individuals. Glycan analysis was done by ultra performance liquid chromatography based
on hydrophilic interactions. In this thesis, it was discovered that in adult subjects diagnosed with T1DM there is a
statistically significant change in the proportion of glycan structures GP2, GP4, GP5, GP7, GP13, GP14, GP17, GP19,
GP21, GP24, GP25, GP27 and GP29. A more detailed study of the derived traits showed a decrease in the proportion of
low-branched glycans, and an increase in highly branched glycans. Furthermore, a reduction in the proportion of
digalactosylated glycans and an increase in the proportion of trigalactosylated and trisialinised glycans is found in T1DM
patients. The proportion of glycans with core fucose was significantly reduced in T1DM patients, while the proportion
of high mannose glycans was significantly increased.
These changes in IgA glycosylation indicate that it has a possible role in the disease progression and the need for further
examination of its prognostic value. |
