Recent years have brought notable progress in the field of IgA nephropathy. Here, we highlight important new directions and latest developments, including successful discovery of several genetic susceptibility loci, formulation of the multihit pathogenesis model, introduction of the Oxford pathology scoring system, and formalization of the Kidney Disease Improving Global Outcomes (KDIGO) consensus treatment guidelines. We focus on the latest genetic findings that confirm a strong contribution of inherited factors and explain some of the geoethnic disparities in disease susceptibility. Most IgA nephropathy susceptibility loci discovered to date encode genes involved in the maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The concerted pattern of interpopulation allelic differentiation across all genetic loci parallels the disease prevalence and correlates with variation in local pathogens, suggesting that multilocus adaptation might have shaped the present-day landscape of IgA nephropathy. Importantly, the 'Intestinal Immune Network for IgA Production' emerged as one of the new targets for potential therapeutic intervention. We place these findings in the context of the multihit pathogenesis model and existing knowledge of IgA immunobiology. Lastly, we provide our perspective on the existing treatment options, discuss areas of clinical uncertainty, and outline ongoing clinical trials and translational studies.Kidney International advance online publication, 16 September 2015; doi:10.1038/ki.2015.252.

New developments in the genetics, pathogenesis, and therapy of IgA nephropathy / Magistroni, Riccardo; D'Agati, Vivette D.; Appel, Gerald B.; Kiryluk, Krzysztof. - In: KIDNEY INTERNATIONAL. - ISSN 0085-2538. - STAMPA. - 88:5(2015), pp. 974-989. [10.1038/ki.2015.252]

New developments in the genetics, pathogenesis, and therapy of IgA nephropathy

MAGISTRONI, Riccardo;
2015

Abstract

Recent years have brought notable progress in the field of IgA nephropathy. Here, we highlight important new directions and latest developments, including successful discovery of several genetic susceptibility loci, formulation of the multihit pathogenesis model, introduction of the Oxford pathology scoring system, and formalization of the Kidney Disease Improving Global Outcomes (KDIGO) consensus treatment guidelines. We focus on the latest genetic findings that confirm a strong contribution of inherited factors and explain some of the geoethnic disparities in disease susceptibility. Most IgA nephropathy susceptibility loci discovered to date encode genes involved in the maintenance of the intestinal epithelial barrier and response to mucosal pathogens. The concerted pattern of interpopulation allelic differentiation across all genetic loci parallels the disease prevalence and correlates with variation in local pathogens, suggesting that multilocus adaptation might have shaped the present-day landscape of IgA nephropathy. Importantly, the 'Intestinal Immune Network for IgA Production' emerged as one of the new targets for potential therapeutic intervention. We place these findings in the context of the multihit pathogenesis model and existing knowledge of IgA immunobiology. Lastly, we provide our perspective on the existing treatment options, discuss areas of clinical uncertainty, and outline ongoing clinical trials and translational studies.Kidney International advance online publication, 16 September 2015; doi:10.1038/ki.2015.252.
2015
16-set-2015
88
5
974
989
New developments in the genetics, pathogenesis, and therapy of IgA nephropathy / Magistroni, Riccardo; D'Agati, Vivette D.; Appel, Gerald B.; Kiryluk, Krzysztof. - In: KIDNEY INTERNATIONAL. - ISSN 0085-2538. - STAMPA. - 88:5(2015), pp. 974-989. [10.1038/ki.2015.252]
Magistroni, Riccardo; D'Agati, Vivette D.; Appel, Gerald B.; Kiryluk, Krzysztof
File in questo prodotto:
File Dimensione Formato  
Magistroni-2015-New developments in the geneti.pdf

Open access

Tipologia: Versione dell'autore revisionata e accettata per la pubblicazione
Dimensione 1.8 MB
Formato Adobe PDF
1.8 MB Adobe PDF Visualizza/Apri
VOR_New developments in the genetics pathogenesis.pdf

Accesso riservato

Tipologia: Versione pubblicata dall'editore
Dimensione 1.9 MB
Formato Adobe PDF
1.9 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1081707
Citazioni
  • ???jsp.display-item.citation.pmc??? 111
  • Scopus 229
  • ???jsp.display-item.citation.isi??? 196
social impact