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001-es BibID:	BIBFORM134812
035-os BibID:	(scopus)105016268170 (wos)001571366900001
Első szerző:	Pócsi Marianna (klinikai laboratóriumi kutató)
Cím:	Comparison of the Effect of CFTR Modulators elexacaftor/tezacaftor/ivacaftor and lumacaftor/ivacaftor via Serum Human Epididymis Protein 4 Concentration in p.Phe508del-CFTR Homozygous Cystic Fibrosis Patients / Pócsi Marianna, Fila Libor, Péterfia Csaba, Halász Adrien, Szanto Tibor G., Mészáros Beáta, Major Judit, Laki István, Szabó Hajnalka, Panyi György, Balogh István, Amaral Margarida D., Macek Jr. Milan, Nagy Jr. Béla
Dátum:	2025
ISSN:	2077-0383
Megjegyzések:	Elevated human epididymis protein 4 (HE4) levels decreased in patients with CF (pwCF) in response to CFTR-specific drugs and negatively correlated with FEV1% predicted values (ppFEV1). Objectives: Although elexacaftor/tezacaftor/ivacaftor (ETI, Kaftrio?) demonstrates more substantial effectiveness than lumacaftor/ivacaftor (LUM/IVA, Orkambi?) in pwCF, plasma biomarkers have not been used to compare treatment efficacy. Hence, our aim was to correlate the change in HE4 levels and the clinical effects of these CFTR modulators (CFTRm). Methods: Serum HE4 concentrations were measured in a total of 123 pwCF homozygous for the p.Phe508del-CFTR variant before treatment and 1?6 months after either ETI or LUM/IVA administration. A correlation between serum HE4 and ppFEV1 was assessed using the Spearman test. HE4 protein levels were also analyzed in the supernatants of p.Phe508del-CFTR CFBE 41o- cells before and after treatment with these CFTRm, and their direct effect on CFTR function was monitored by the whole-cell patch-clamp technique. Results: Serum HE4 levels were reduced below baseline after 3 months of either ETI or LUM/IVA (mean delta HE4: ?38.5 vs. ?18.5 pmol/L, respectively) when the mean change of ppFEV1 was 13.6 vs. 1.6% and remained decreased up to 6 months. A significant inverse correlation between HE4 and ppFEV1 was observed in both study cohorts (r = ?0.537 and r = ?0.575, respectively; p < 0.0001). In agreement with ex vivo results, the effect on p.Phe508del-CFTR was more pronounced by ETI than LUM/IVA in CFBE cells, showing a larger improvement in p.Phe508del-CFTR function and reductions in HE4 levels at 24 h. Conclusions: Serum HE4 negatively correlates with lung function improvement and monitors better drug efficacy in pwCF under ETI than LUM/IVA.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk cystic fibrosis HE4 CFTR modulator ppFEV1 biomarker treatment efficacy
Megjelenés:	Journal of Clinical Medicine. - 14 : 17 (2025), p. 1-18. -
További szerzők:	Fila, Libor Péterfia Csaba Halász Adrienn Szántó Gábor Tibor (1980-) (vegyész) Mészáros Beáta (1985-) (molekuláris biológus, mikrobiológus) Major Judit Laki István Szabó Hajnalka Panyi György (1966-) (biofizikus) Balogh István (1972-) (molekuláris biológus, genetikus) Amaral, Margarida D. Macek Jr., Milan Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos)
Pályázati támogatás:	FK 135327 OTKA UID/04046/2025 Egyéb 00064203/6003 Egyéb
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM113535
035-os BibID:	(scopus)85153208380 (WoS)001129085700001
Első szerző:	Pócsi Marianna (klinikai laboratóriumi kutató)
Cím:	Human epididymis protein 4 (HE4) plasma concentration inversely correlates with the improvement of cystic fibrosis lung disease in p.Phe508del-CFTR homozygous cases treated with the CFTR modulator lumacaftor/ivacaftor combination / Marianna Pócsi, Zsolt Fejes, Zsolt Bene, Attila Nagy, István Balogh, Margarida D. Amaral, Milan Macek Jr., Béla Nagy Jr.
Dátum:	2023
ISSN:	1569-1993 1873-5010
Megjegyzések:	Background: We previously documented that elevated HE4 plasma concentration decreased in people with CF (pwCF) bearing the p.Gly551Asp-CFTR variant in response to CFTR modulator (CFTRm) ivacaftor (IVA), and this level was inversely correlated with the FEV1% predicted values (ppFEV1). Although the effectiveness of lumacaftor (LUM)/IVA in pwCF homozygous for the p.Phe508del-CFTR variant has been evaluated, plasma biomarkers were not used to monitor treatment efficacy thus far. Methods: Plasma HE4 concentration was examined in 68 pwCF drawn from the PROSPECT study who were homozygous for the p.Phe508del-CFTR variant before treatment and at 1, 3, 6 and 12 months after administration of LUM/IVA therapy. Plasma HE4 was correlated with ppFEV1 using their absolute and delta values. The discriminatory power of delta HE4 was evaluated for the detection of lung function improvements based on ROC-AUC analysis and multiple regression test. Results: HE4 plasma concentration was significantly reduced below baseline following LUM/IVA administration during the entire study period. The mean change of ppFEV1 was 2.6% (95% CI, 0.6 to 4.5) by 6 months of therapy in this sub-cohort. A significant inverse correlation between delta values of HE4 and ppFEV1 was observed especially in children with CF (r=-0.7053; p<0.0001). Delta HE4 predicted a 2.6% mean change in ppFEV1 (AUC: 0.7898 [95% CI 0.6823?0.8972]; P < 0.0001) at a cut-off value of -10.7 pmol/L. Moreover, delta HE4 independently represented the likelihood of being a responder with ? 5% delta ppFEV1 at 6 months (OR: 0.89, 95% CI: 0.82?0.95; P = 0.001). Conclusions: Plasma HE4 level negatively correlates with lung function improvement assessed by ppFEV1 in pwCF undergoing LUM/IVA CFTRm treatment. ? 2023
Tárgyszavak:	Orvostudományok Klinikai orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal Of Cystic Fibrosis. - 22 : 6 (2023), p. 1085-1092. -
További szerzők:	Fejes Zsolt (1988-) (molekuláris biológus) Bene Zsolt (1981-) (orvos) Nagy Attila Csaba (1981-) (megelőző orvostan és népegészségtan szakorvos, epidemiológus) Balogh István (1972-) (molekuláris biológus, genetikus) Amaral, Margarida D. Macek Jr., Milan Nagy Béla Jr. (1980-) (labordiagnosztikai szakorvos)
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