Is complement the main accomplice in IgA nephropathy? From initial observations to potential complement-targeted therapies

Molecular Immunology, vol. 140, pp. 1–11

Abstract

IgA Nephropathy (IgAN) is the main cause of primary glomerulonephritis, globally. This disease is associated with a wide range of clinical presentations, variable prognosis and a spectrum of histological findings. More than fifty years after its first description, this heterogeneity continues to complicate efforts to understand the pathogenesis. Nevertheless, involvement of the complement system in IgAN was identified early on. Dysfunction of the immunoglobulin A (IgA) system, the principal offender in this disease, including modification of isoforms and glycoforms of IgA1, the nature of immune complexes and autoantibodies to galactose deficient IgA1 might all be responsible for complement activation in IgAN. However, the specific mechanisms engaging complement are still under examination. Research in this domain should allow for identification of patients that may benefit from complement-targeted therapy, in the foreseeable future.

Authors 5

1. Marie-Bénédicte Le Stang

   Centre National de la Recherche Scientifique · Inserm · Université Paris Cité · Centre de Recherche sur l'Inflammation

   Affiliation as printed

   Université de Paris, Center for Research on Inflammation, Inserm U1149 & CNRS ERL8252, Inflamex Laboratory, Paris, France

2. Patrick James Gleeson

   Centre National de la Recherche Scientifique · Inserm · Royal College of Physicians of Ireland · Université Paris Cité · Centre de Recherche sur l'Inflammation

   Affiliation as printed

   Université de Paris, Center for Research on Inflammation, Inserm U1149 & CNRS ERL8252, Inflamex Laboratory, Paris, France; Royal College of Physicians of Ireland, Division of Nephrology, Dublin, Ireland

   Royal College of Physicians of Ireland, Division of Nephrology, Dublin, Ireland

   Université de Paris, Center for Research on Inflammation, Inserm U1149 & CNRS ERL8252, Inflamex Laboratory, Paris, France

3. Mohamed R. Daha Aachen Department of Nephrology, Leiden University Medical Center

   University Medical Center Groningen · Leiden University Medical Center

   Affiliation as printed

   Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands; Department of Nephrology, University Medical Center Groningen, Groningen, the Netherlands

   Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands

   Department of Nephrology, University Medical Center Groningen, Groningen, the Netherlands

4. Renato C. Monteiro

   Centre National de la Recherche Scientifique · Inserm · Université Paris Cité · Assistance Publique – Hôpitaux de Paris · Centre de Recherche sur l'Inflammation · Hôpital Bichat-Claude-Bernard

   Affiliation as printed

   Université de Paris, Center for Research on Inflammation, Inserm U1149 & CNRS ERL8252, Inflamex Laboratory, Paris, France; Laboratory of Immunological Dysfunction, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat-Claude Bernard University Hospital, Paris, France

   Laboratory of Immunological Dysfunction, Assistance Publique-Hôpitaux de Paris (AP-HP), Bichat-Claude Bernard University Hospital, Paris, France

   Université de Paris, Center for Research on Inflammation, Inserm U1149 & CNRS ERL8252, Inflamex Laboratory, Paris, France

5. Cees van Kooten corresponding Aachen Department of Nephrology, Leiden University Medical Center

   Leiden University Medical Center

   Affiliation as printed

   Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands. Electronic address: C.van_Kooten@lumc.nl

   Department of Nephrology, Leiden University Medical Center, Leiden, the Netherlands