Aktivnost eritrocitne glutation S-transferaze u djece oboljele od HenochSchönleinove purpure [Erythrocyte glutathione S-transferase activity in children with Henoch-Schönlein purpura]

Frković, Marijan (2020) Aktivnost eritrocitne glutation S-transferaze u djece oboljele od HenochSchönleinove purpure [Erythrocyte glutathione S-transferase activity in children with Henoch-Schönlein purpura]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Henoch-Schönlein purpura (HSP) is the most common vasculitis of the childhood. Among all possible symptoms / complications, nephritis (HSPN) is the main and almost only cause of morbidity and mortality in HSP. The aim of this study was to investigate the value of erythrocyte glutathione S-transferase (eGST) activity as an early predictor of nephritis in HSP. ----- Subjects and methods: Ninety-seven children with HSP were enrolled into the study. The control group consisted of 52 children without clinical and laboratory signs of inflammation. In all patients e-GST activity was determined spectrometrically from the whole blood samples, after incubation with a commercial GST assay at the time of enrolment and twice more in regular intervals during follow up period of six months. In children from the control group e-GST activity was determined at the time of enrolment. ----- Results: At the beginning of the disease the e-GST activity values were significantly higher in the group of patients with HSPN compared to the group of HSP patients without nephritis: median (interquartile range) 5,70 U/gHb (4,38-7,50 U/gHb) compared to 3,10 U/gHb (2,20-4,20 U/gHb); P˂0,001. Similar results were obtained after the comparison of the patients with HSPN and control group: 5,70 U/gHb (4,38-7,50 U/gHb) vs. 3,13 U/gHb (1,91-4,20 U/gHb); P˂0,001. There were no statistically significant differences between the group of HSP patients without nephritis and a control group (P=0,837). During the follow up period of six months, a significant decrease of e-GST activity was observed in the HSPN patients, but it was still significantly higher compared to the group of HSP patients without nephritis (P˂0,001 / P˂0,001). In the ROC analysis of the e-GST activity determination value in the prediction of HSP nephritis, at the e-GST values >4,1 U/gHb a significant area under the curve (AUC) of 91.1% (P < 0.001) and sensitivity of 90.5% and specificity of 72.7% was found at the beginning of the study. The sensitivity of the nephritis detection tests decreased, and the specificity increased during the follow up period. No significant correlation between e-GST activity and severity of skin changes, or used therapy was found. Among the routine laboratory tests, a consistent, statistically significant, positive correlation was found only between e-GST activity and the number of erythrocytes per mm3 in urine samples. ----- Conclusion: e-GST activity is a reliable, independent marker of early nephritis risk assessment in children with HSP. As a sensitive and specific, feasible and inexpensive laboratory test, it has potential practical utility in the diagnostic algorithm and monitoring of the children with HSP.

Abstract in Croatian

Uvod: Henoch-Schönleinova purpura (HSP) najčešći je vaskulitis dječje dobi. Nefritis koji se može razviti u sklopu bolesti (HSPN), glavni je i gotovo jedini uzrok morbiditeta i mortaliteta oboljele djece. Cilj rada bio je istražiti vrijednost određivanja aktivnosti eritrocitne glutation S-transferaze (e-GST) kao ranog prediktora razvoja nefritisa u sklopu navedene bolesti. ----- Ispitanici i metode: U istraživanje je uključeno 97 djece s dijagnozom HSP (55 djece bez nefritisa i 42 djece s nefritisom) i 52 djece kontrolne skupine. U svih je bolesnika aktivnost e-GST određena na početku bolesti te nakon tri i šest mjeseci, a u kontrolnoj skupini jednokratno. Aktivnost e-GST određena je spektrometrijski u pripremljenom uzorku pune krvi, nakon inkubacije s komercijalnim GST testom. ----- Rezultati: Aktivnost e-GST u skupini djece s HSPN bila je na početku bolesti statistički značajno veća u odnosu na skupinu djece s HSP bez nefritisa: medijan (interkvartilni raspon) 5,70 U/gHb (4,38 − 7,50 U/gHb) prema 3,10 U/gHb (2,20 − 4,20 U/gHb); P < 0,001 (Mann-Whitneyjev test), kao i u odnosu na kontrolu: 5,70 U/gHb (4,38 − 7,50 U/gHb) prema 3,13 U/gHb (1,91 − 4,20 U/gHb); P < 0,001 (KruskalWallisov test). Razlike između skupine HSP bolesnika bez nefritisa u odnosu na kontrolnu skupinu djece nisu bile statistički značajne (P = 0,837, Kruskal-Wallisov test). U skupini bolesnika s HSPN tijekom šestomjesečnog praćenja došlo je do značajnog pada aktivnosti e-GST (P = 0,018), ali ona je i dalje bila statistički značajno veća u odnosu na skupinu HSP bolesnika bez nefritisa (P < 0,001 / P < 0,001 (Mann-Whitneyjev test)). Pri ROC analizi vrijednosti određivanja aktivnosti e-GST u predikciji nastanka nefritisa, na početku istraživanja kod vrijednosti eGST > 4,1 U/gHb nađena je značajna površina ispod krivulje (AUC) od 91,1 % (P < 0,001) te osjetljivost od 90,5 % i specifičnost od 72,7 %. Nakon tri, odnosno šest mjeseci, pala je osjetljivost, a povećana specifičnost testova u otkrivanju nefritisa. U oboljelih nije nađena korelacija aktivosti e-GST s izraženošću kožnih promjena, primijenjenom terapijom niti njezinim trajanjem. Među praćenim laboratorijskim nalazima, konzistentna, statistički značajna, pozitivna korelacija utvrđena je samo između aktivnosti e-GST i broja E/mm3 urina (P < 0,001 (Spearmanov koeficijent korelacije)). ----- Zaključak: Rezultati istraživanja ukazuju da je aktivnost e-GST pouzdan, neovisan marker rane procjene rizika od razvoja nefritisa u djece oboljele od HSP. Određivanje aktivnosti navedenog enzima u serumu, kao osjetljiva i specifična, jednostavno izvediva i jeftina laboratorijska pretraga, ima potencijalnu praktičnu primjenu u dijagnostičkom algoritmu obrade i praćenja bolesnika s HSP.

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