Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy - CNRS - Centre national de la recherche scientifique Accéder directement au contenu
Article Dans Une Revue PLoS ONE Année : 2020

Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy

Christelle Michiels
  • Fonction : Auteur
  • PersonId : 925183
Christina Zeitz
Connectez-vous pour contacter l'auteur

Résumé

Melanoma-associated retinopathy (MAR) is a rare paraneoplastic retinal disorder usually occurring in the context of metastatic melanoma. Patients present with night blindness, photopsias and a constriction of the visual field. MAR is an auto-immune disorder characterized by the production of autoantibodies targeting retinal proteins, especially autoantibodies reacting to the cation channel TRPM1 produced in melanocytes and ON-bipolar cells. TRPM1 has at least three different isoforms which vary in the N-terminal region of the protein. In this study, we report the case of three new MAR patients presenting different anti-TRPM1 autoantibodies reacting to the three isoforms of TRPM1 with variable binding affinity. Two sera recognized all isoforms of TRPM1, while one recognized only the two longest isoforms upon immunolocalization studies on overexpressing cells. Similarly, the former two sera reacted with all TRPM1 isoforms on western blot, but an immunoprecipitation enrichment step was necessary to detect all isoforms with the latter serum. In contrast, all sera labelled ON-bipolar cells on Tprm1+/+ but not on Trpm1-/- mouse retina as shown by co-immunolocalization. This confirms that the MAR sera specifically detect TRPM1. Most likely, the anti-TRPM1 autoantibodies of different patients vary in affinity and concentration. In addition, the binding of autoantibodies to TRPM1 may be conformation-dependent, with epitopes being inaccessible in some constructs (truncated polypeptides versus full-length TRPM1) or applications (western blotting versus immunohistochemistry). Therefore, we propose that a combination of different methods should be used to test for the presence of anti-TRPM1 autoantibodies in the sera of MAR patients.
Fichier principal
Vignette du fichier
journal.pone.0231750.pdf (1.63 Mo) Télécharger le fichier
Origine : Publication financée par une institution
Loading...

Dates et versions

inserm-02574509 , version 1 (14-05-2020)

Identifiants

Citer

Juliette Varin, Margaret M Reynolds, Nassima Bouzidi, Sarah Tick, Juliette Wohlschlegel, et al.. Identification and characterization of novel TRPM1 autoantibodies from serum of patients with melanoma-associated retinopathy. PLoS ONE, 2020, 15 (4), pp.e0231750. ⟨10.1371/journal.pone.0231750⟩. ⟨inserm-02574509⟩
117 Consultations
119 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More