TY - JOUR
T1 - Identification of autoantibodies against TRPM1 in patients with paraneoplastic retinopathy associated with ON bipolar cell dysfunction
AU - Kondo, Mineo
AU - Sanuki, Rikako
AU - Ueno, Shinji
AU - Nishizawa, Yuji
AU - Hashimoto, Naozumi
AU - Ohguro, Hiroshi
AU - Yamamoto, Shuichi
AU - Machida, Shigeki
AU - Terasaki, Hiroko
AU - Adamus, Grazyna
AU - Furukawa, Takahisa
PY - 2011
Y1 - 2011
N2 - Background: Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction. Methodology/Principal Findings: We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response with normal OFF response, indicating that the defect is in the signal transmission between photoreceptors and ON bipolar cells. We also investigated the sera of 26 patients with MAR for autoantibodies against TRPM1 because MAR patients are known to exhibit retinal ON bipolar cell dysfunction. Two of the patients were found to have autoantibodies against TRPM1 in their sera. Conclusion/Significance: Our study reveals TRPM1 to be one of the autoantigens targeted by autoantibodies in at least some patients with CAR or MAR associated with retinal ON bipolar cell dysfunction.
AB - Background: Paraneoplastic retinopathy (PR), including cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR), is a progressive retinal disease caused by antibodies generated against neoplasms not associated with the eye. While several autoantibodies against retinal antigens have been identified, there has been no known autoantibody reacting specifically against bipolar cell antigens in the sera of patients with PR. We previously reported that the transient receptor potential cation channel, subfamily M, member 1 (TRPM1) is specifically expressed in retinal ON bipolar cells and functions as a component of ON bipolar cell transduction channels. In addition, this and other groups have reported that human TRPM1 mutations are associated with the complete form of congenital stationary night blindness. The purpose of the current study is to investigate whether there are autoantibodies against TRPM1 in the sera of PR patients exhibiting ON bipolar cell dysfunction. Methodology/Principal Findings: We performed Western blot analysis to identify an autoantibody against TRPM1 in the serum of a patient with lung CAR. The electroretinograms of this patient showed a severely reduced ON response with normal OFF response, indicating that the defect is in the signal transmission between photoreceptors and ON bipolar cells. We also investigated the sera of 26 patients with MAR for autoantibodies against TRPM1 because MAR patients are known to exhibit retinal ON bipolar cell dysfunction. Two of the patients were found to have autoantibodies against TRPM1 in their sera. Conclusion/Significance: Our study reveals TRPM1 to be one of the autoantigens targeted by autoantibodies in at least some patients with CAR or MAR associated with retinal ON bipolar cell dysfunction.
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U2 - 10.1371/journal.pone.0019911
DO - 10.1371/journal.pone.0019911
M3 - Article
C2 - 21611200
AN - SCOPUS:79956105681
SN - 1932-6203
VL - 6
JO - PloS one
JF - PloS one
IS - 5
M1 - e19911
ER -