| Abstract | Uvod: IgA vaskulitis (IgAV) najčešći je vaskulitis dječje dobi, a obilježava ga sistemska upala u malim krvnim žilama. Obično je povoljnog ishoda, međutim moguće su akutne komplikacije s gastrointestinalnim manifestacijama i nefritis kao kronična, dugoročna komplikacija. Iako su u IgAV-u ispitivani različiti biomarkeri, patogeneza bolesti još uvijek nije poznata niti su poznati biomarkeri koji bi mogli ukazivati na aktivnu bolest i predvidjeti moguća oštećenja.
Ciljevi istraživanja: Ispitati koncentraciju Gd-IgA1, HMGB1, RAGE i PCDH1 u serumu i urinu u djece s IgAV-om i u kontrolnih ispitanika te utvrditi postoji li povezanost s kliničkim značajkama, laboratorijskim nalazima, aktivnosti bolesti i predikcijom pojavnosti nefritisa u djece s IgAV-om.
Ispitanici i metode: Prospektivno istraživanje provedeno je u razdoblju od siječnja 2020. do listopada 2023., a uključilo je 86 djece s IgAV-om i 70 djece iz kontrolne skupine. Koncentracije Gd-IgA1, HMGB1, RAGE i PCDH1 u serumu i urinu određene su imunoenzimskom (ELISA) metodom u akutnoj fazi bolesti i nakon šest mjeseci praćenja u djece s IgAV-om te jednokratno u kontrolnoj skupini.
Rezultati: Koncentracija HMGB1, RAGE i PCDH1 u serumu te koncentracija Gd-IgA1, HMGB1, RAGE i PCDH1 u urinu su statistički značajno veće u djece s IgAV-om nego u kontrolnih ispitanika (p<0,001). U djece s IgAV-om uočena je statistički značajna razlika u vrijednostima koncentracija HMGB1 (5573 pg/ml vs. 3477 pg/ml vs. 1088 pg/ml, p<0,001) i RAGE (309 pg/ml vs. 302,4 pg/ml vs. 201,3 pg/ml, p=0,012) u serumu na početku bolesti u usporedbi s koncentracijom izmjerenom nakon šest mjeseci praćenja te između kontrolne skupine. Regresijska analiza nije izdvojila nijedan od ispitivanih biomarkera kao prediktor nefritisa. Koncentracije Gd-IgA1, HMGB1, RAGE i PCDH1 u urinu su pozitivno korelirale s omjerom albumina i kreatinina u urinu na početku bolesti, a HMGB1, RAGE i PCDH1 i u razdoblju praćenja. Serumska koncentracija RAGE značajno je pozitivno korelirala s koštano-mišićnim manifestacijama IgAV-a (τ=0,185, p=0,030), kao i PCDH1 u urinu (τ=0,238, p=0,012). Logistička regresija izdvojila je serumski Gd-IgA1 (CI 0,943-0,982, p=0,028), RAGE (CI 0,983-0,998, p=0,026) i PCDH1 (CI 1,021-1,137, p=0,012) te HMGB1 u urinu (CI 1,000-1,002, p=0,026) kao prediktore pojavnosti artritisa. Koncentracija HMGB1 u urinu PCDH1 u serumu značajno je pozitivno bila povezana s nalazom mezangijske hipercelularnosti (τ=0,450, p=0,042), a negativno s nalazom endokapilarne hipercelularnosti (τ= -0,478, p=0,030) u bioptiranih bolesnika.
Zaključak: Dobiveni rezultati upućuju na moguću povezanost Gd-IgA1, HMGB1, RAGE i PCDH1 s IgAV-om pri čemu HMGB1 i RAGE pokazuju povišene vrijednosti tijekom praćenja te bi mogli biti pokazatelj aktivnosti bolesti. Ispitivani biomarkeri u ovom istraživanju nisu bili prediktori pojavnosti nefritisa, najvažnije dugoročne komplikacije IgAV-a. Međutim, HMGB1 i PCDH1 mogu imati potencijal u praćenju bolesnika koji su razvili nefritis zbog pozitivne povezanosti s ishodom nefritisa odnosno s nalazom bioptata bubrega. |
| Abstract (english) | Introduction: IgA vasculitis (IgAV) is the most common childhood vasculitis characterized by systemic inflammation of small blood vessels. It usually has a favorable outcome, however, acute complications with gastrointestinal manifestations and nephritis as chronic, long term complication are possible. Although various biomarkers have been investigated in IgAV, the pathogenesis of the disease is not elucidated yet, nor are known biomarkers that could indicate active disease and predict possible damage.
Objectives: To examine the concentrations of Gd-IgA1, HMGB1, RAGE nad PCDH1 in serum and urine in children with IgAV and in control subjects and to determine whether there is an association with clinical features, laboratory findings, disease activity and prediction of nephritis in children with IgAV.
Subjects and methods: A prospective study was conducted in the period from January 2020 until October 2023, and included 86 children with IgAV and 70 children from the control group. Concentrations of Gd-IgA1, HMGB1, RAGE and PCDH1 in serum and urine were determined by immunoenzymatic (ELISA) method in the acute phase of the disease and after six months follow up interval in children with IgAV and once in the control group.
Results: Concentrations of HMGB1, RAGE and PCDH1 in sera and concentrations of Gd-IgA1, HMGB1, RAGE and PCDH1 in urine were statistically significantly higher in children with IgAV than in the control group (p<0.001). In children with IgAV, a statistically significant difference was observed in concentrations of HMGB1 (5573 pg/mL vs. 3477 pg/mL vs. 1088 pg/mL, p<0.001) and RAGE (309 pg/mL vs. 302.4 pg/mL vs. 201.3 pg/mL, p=0.012) in sera at the onset of the disease compared to the concentration measured after six months follow up and between the control group. Regression analysis didn't reveal any of investigated biomarkers as a predictor of nephritis. Concentrations of Gd-IgA1, HMGB1, RAGE and PCDH1 in urine positively correlated with the urine albumine to creatinine ratio at the onset of the disease, and HMGB1, RAGE and PCDH1 in the follow up interval. Serum RAGE were significantly positively correlated with musculoskeletal manifestations of IgAV (τ=0.185, p=0.030), as well as urinary PCDH1 (τ=0.238, p=0.012). Logistic regression distinguished serum Gd-IgA1 (CI 0.943-0.982, p=0.028), RAGE (CI 0.983-0.998, p=0.026) and PCDH1 (CI 1.021-1.137, p=0.012) and urinary HMGB1 (CI 1.000-1.002, p=0.026) as predictors of the incidence of arthritis. Concentration of HMGB1 in urine was significantly positively correlated with the outcome of nephritis (τ=0.287, p=0.044). Concentration of PCDH1 in the serum was significantly positively correlated with the finding of mesangial hypercellularity (τ=0.450, p=0.042) and negatively with the finding of mesangial hypercellularity (τ= -0.478, p=0.030) in biopsied patients.
Conclusion: Results imply a possible association of Gd-IgA1, HMGB1, RAGE and PCDH1 with IgAV, whereby HMGB1 and RAGE show elevated values during the disease follow up and could be an indicator of disease activity. The investigated biomarkers in this study were not predictors of the occurrence of nephritis, the most important long term complication of IgAV. However, HMGB1 and PCDH1 could have a potential role in the follow up of patients with nephritis due to a positive association with the outcome of nephritis and with the renal biopsy findings. |
