0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Comment & Response |

Neuronal Antibodies in Creutzfeldt-Jakob Disease—Reply

Francesc Graus, MD, PhD1,2; Josep Dalmau, MD, PhD2,3,4
[+] Author Affiliations
1Department of Neurology, Hospital Clínic, Barcelona, Spain
2Institut d’Investigació Biomèdica August Pi i Sunyer, Barcelona, Spain
3Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain
4Department of Neurology, University of Pennsylvania, Philadelphia
JAMA Neurol. 2014;71(4):514-515. doi:10.1001/jamaneurol.2014.30.
Text Size: A A A
Published online

Extract

In Reply Takahashi and colleagues detected in the cerebrospinal fluid of a patient with Creutzfeldt-Jakob disease antibodies against the NR2b subunit of the N-methyl-D-aspartate receptor (NMDAR) confirmed by immunoblot and immunofluorescence on human embryonic kidney 293 cells transfected with NR1 and NR2B subunits of the NMDAR.1 They concluded that antibodies against NMDAR do not rule out the diagnosis of Creutzfeldt-Jakob disease. Takahashi and colleagues do not understand that our article was focused on determining antibodies to neuronal cell-surface proteins including NMDARs and other synaptic receptors.2 These antibodies are against conformation-dependent epitopes and do not react with immunoblots of the protein. In addition, Takahashi and colleagues do not understand that anti-NMDAR encephalitis associates with antibodies against a well-defined epitope in the N-terminal region of the NR1 subunit of the NMDAR.3 These antibodies cause capping and internalization of the receptor, leading to a decrease of the density of cell surface and synaptic NMDAR and a reduction of NMDAR-synaptic currents.4 These antibodies show intense reactivity with the neuropil of brain along with robust immunolabeling of the neuronal cell surface and are demonstrated with human embryonic kidney cells transfected with NR1 alone or combined with NR2B.5 These data5 have been in the literature since 2008. The lack of significance of antibodies against NR2B was also reported in 2008, when we assessed samples (all supposedly with NMDAR antibodies) from Takahashi6 showing that those we identified (masked of clinical information) with NR1 antibodies were found to be highly specific for anti-NMDAR encephalitis, while those that were NR1 antibody negative (supposedly NR2B positive) had no syndrome specificity, lacking clinical utility. Moreover, we did not find any reactivity with the neuropil of brain or cultures of neurons with those supposedly NR2B antibody positive. Therefore, it is difficult to understand why Takahashi and colleagues still confuse NR1 with NR2B antibodies. Indeed, most reports by Takahashi refer to antibodies reacting with NR2B linear epitopes or peptides that have never been convincingly shown to react with the neuropil of brain or cell surface of neurons. In their article1 where they suggest binding of NR2B antibodies with human embryonic kidney cells, the unusual staining pattern and absence of colocalization studies raise serious concerns about their interpretation. These authors have never demonstrated any pathogenic effect of NR2B antibodies and therefore attributing to these antibodies1 the findings obtained by other investigators with NR14 is highly misleading. The numerous disorders that Takahashi and colleagues have reported in association with NR2B antibodies, including Rasmussen encephalitis, epilepsia partialis continua, viral encephalitis, neurodegenerative diseases, paraneoplastic opsoclonus, and encephalitis6 (to which now Creutzfeldt-Jakob disease has been added), leads to a modified interpretation of their conclusion: cerebrospinal fluid antibodies against NR2B (NMDAR) do not rule out the diagnosis of any disease.

Topics

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview

Figures

Tables

References

Correspondence

April 1, 2014
Koji Fujita, MD, PhD; Keiko Tanaka, MD, PhD; Yukitoshi Takahashi, MD, PhD
1Department of Clinical Neuroscience, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan
2Department of Neurology, Kanazawa Medical University, Ishikawa, Japan
3National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan
JAMA Neurol. 2014;71(4):514. doi:10.1001/jamaneurol.2014.27.
CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

279 Views
0 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

See Also...
Jobs
brightcove.createExperiences();