Rosanna Coppo1, Licia Peruzzi2, Elisa Loiacono1, Massimilano Bergallo3, Alexandra Krutova4, Maria Luisa Russo1, Enrico Cocchi2, Alessandro Amore2, Sigrid Lundberg5, Dita Maixnerova6, Vladimir Tesar6, Agnieszka Perkowska-Ptasińska7, Magdalena Durlik7, Dimitris Goumenos8, Miltiadis Gerolymos8, Kresimir Galesic9, Luka Toric9, Aikaterini Papagianni10, Maria Stangou10, Malgorzata Mizerska-Wasia Membek11, Loreto Gesualdo12, Eustacchio Montemurno12, Luisa Benozzi13, Stefano Cusinato13, Tomasz Hryszko14, Marian Klinger15, Dorota Kamińska15, Magdalena Krajewska15. 1. Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy. 2. Department of Nephrology, Dialysis and Transplantation, Regina Margherita Hospital, Turin, Italy. 3. Department of Public Health and Pediatric Sciences, University of Turin, Turin, Italy. 4. Department of Pediatrics, Regional Children's Clinical Hospital, Vladivostok, Russia. 5. Division of Nephrology, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institutet, Stockholm, Sweden. 6. Department of Nephrology, First Faculty of Medicine and General University Hospital, Prague, Czech Republic. 7. Department of Transplantation Medicine and Nephrology, Medical University of Warsaw, Warsaw, Poland. 8. Department of Nephrology, University Hospital of Patras, Patras, Greece. 9. Department of Nephrology, Dubrava University Hospital, Zagreb, Croatia. 10. Department of Nephrology, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 11. Department of Pediatrics and Nephrology, Medical University of Warsaw, Warsaw, Poland. 12. Department of Nephrology, Emergency and Transplantation, University of Bari, Bari, Italy. 13. Department of Nephrology, Borgomanero Hospital, Borgomanero, Italy. 14. Department of Nephrology, Transplantation and Dialysis, Medical University of Bialystok, Bialystok, Poland. 15. Department of Nephrology and Transplantation Medicine, Wroclaw Medical University, Wroclaw, Poland.
Abstract
BACKGROUND: Complement is thought to play a role in immunoglobulin A nephropathy (IgAN), though the activating mechanisms are unknown. This study focused on the gene expression of CD46 and CD55, two key molecules for regulating C3 convertase activity of lectin and alternative complement pathways at a cellular level. METHODS: The transcriptional expression in peripheral white blood cells (WBCs) of CD46 and CD55 was investigated in 157 patients enrolled by the Validation of the Oxford Classification of IgAN group, looking for correlations with clinical and pathology features and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous median follow-up of 6.4 (interquartile range 2.8-10.7) years and were divided into progressors and non-progressors according to the median value of their velocity of loss of renal function per year (-0.41 mL/min/1.73 m2/year). RESULTS: CD46 and CD55 messenger RNA (mRNA) expression in WBCs was not correlated with eGFR values or proteinuria at sampling. CD46 mRNA was significantly correlated with eGFR decline rate as a continuous outcome variable (P = 0.014). A significant difference was found in CD46 gene expression between progressors and non-progressors (P = 0.013). CD46 and CD55 mRNA levels were significantly correlated (P < 0.01), although no difference between progressors and non-progressors was found for CD55 mRNA values. The prediction of progression was increased when CD46 and CD55 mRNA expressions were added to clinical data at renal biopsy (eGFR, proteinuria and mean arterial blood pressure) and Oxford MEST-C (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, presence of any crescents) score. CONCLUSIONS: Patients with progressive IgAN showed lower expression of mRNA encoding for the complement inhibitory protein CD46, which may implicate a defective regulation of C3 convertase with uncontrolled complement activation.
BACKGROUND: Complement is thought to play a role in immunoglobulin A nephropathy (IgAN), though the activating mechanisms are unknown. This study focused on the gene expression of CD46 and CD55, two key molecules for regulating C3 convertase activity of lectin and alternative complement pathways at a cellular level. METHODS: The transcriptional expression in peripheral white blood cells (WBCs) of CD46 and CD55 was investigated in 157 patients enrolled by the Validation of the Oxford Classification of IgAN group, looking for correlations with clinical and pathology features and estimated glomerular filtration rate (eGFR) modifications from renal biopsy to sampling. Patients had a previous median follow-up of 6.4 (interquartile range 2.8-10.7) years and were divided into progressors and non-progressors according to the median value of their velocity of loss of renal function per year (-0.41 mL/min/1.73 m2/year). RESULTS:CD46 and CD55 messenger RNA (mRNA) expression in WBCs was not correlated with eGFR values or proteinuria at sampling. CD46 mRNA was significantly correlated with eGFR decline rate as a continuous outcome variable (P = 0.014). A significant difference was found in CD46 gene expression between progressors and non-progressors (P = 0.013). CD46 and CD55 mRNA levels were significantly correlated (P < 0.01), although no difference between progressors and non-progressors was found for CD55 mRNA values. The prediction of progression was increased when CD46 and CD55 mRNA expressions were added to clinical data at renal biopsy (eGFR, proteinuria and mean arterial blood pressure) and Oxford MEST-C (mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, presence of any crescents) score. CONCLUSIONS:Patients with progressive IgAN showed lower expression of mRNA encoding for the complement inhibitory protein CD46, which may implicate a defective regulation of C3 convertase with uncontrolled complement activation.
Authors: Dalia Mahmoud Eldewi; Alshaymaa M Alhabibi; Hanaa Mohammed Eid El Sayed; Sammar Ahmed Kasim Mahmoud; Sanaa Mohammed El Sadek; Rasha Mahmoud Gouda; Mohammed Abd El Malik Hassan; Amal H Ibrahim; Naglaa F Abd El Haliem Journal: Int J Gen Med Date: 2019-09-16
Authors: Marek Cernoch; Petra Hruba; Marek Kollar; Petra Mrazova; Lucia Stranavova; Alena Lodererova; Eva Honsova; Ondrej Viklicky Journal: Front Immunol Date: 2018-10-09 Impact factor: 7.561