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Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP

From the Department of Neurology (M.I., M.T., S.M., Y.K., T.N., H.K., M.K., N.H., F.T., G.S.), Nagoya University Graduate School of Medicine; Institute for Advanced Research (M.K.), Nagoya University; and Department of Speech Pathology and Audiology (M.Y.), Aichi Gakuin University School of Health Science, Aichi, Japan.

Address correspondence and reprint requests to Dr. Gen Sobue, Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 467-0048, Japan sobueg{at}med.nagoya-u.ac.jp

Objective: Chronic inflammatory demyelinating polyneuropathy (CIDP) is characterized by immune-mediated peripheral demyelination. Although corticosteroid, IV immunoglobulin (IVIg) and plasma exchange have been established as the most effective therapeutics, subpopulations of patients show little or no response to either of these therapies. In this study, we examined whether particular genetic factors influence the therapeutic responsiveness of patients with CIDP.

Methods: One hundred Japanese patients categorized as responders or nonresponders to IVIg therapy participated in our study. We performed an association analysis with single nucleotide polymorphisms (SNPs) and haplotype studies between the IVIg responders and nonresponders.

Results: Two separate SNPs, corresponding to TAG-1 (transient axonal glycoprotein 1) and CLEC10A (C-type lectin domain family 10, member A), showed strong significant differences between responders and nonresponders. Haplotype analysis of a series of expanded SNPs, from TAG-1 or CLEC10A, showed that only TAG-1 included a significant haplotype within 1 linkage disequilibrium block, which accommodates IVIg responsiveness. Diplotype analysis of TAG-1 also supported this observation.

Conclusions: Transient axonal glycoprotein 1 is a crucial molecule involved in IV immunoglobulin responsiveness in Japanese patients with chronic inflammatory demyelinating polyneuropathy.

Abbreviations: CIDP = chronic inflammatory demyelinating polyneuropathy; CMAP = compound muscle action potential; dbSNP = Single Nucleotide Polymorphism database; IVIg = IV immunoglobulin; LD = linkage disequilibrium; PNS = peripheral nervous system; SAP = shrimp alkaline phosphatase; SNP = single nucleotide polymorphism.

Supplemental data at www.neurology.org

Editorial, page 1344

e-Pub ahead of print on September 23, 2009, at www.neurology.org.

Supported by the Ministry of Health, Labor and Welfare of Japan.

Disclosure: The authors report no disclosures.

Received April 4, 2009. Accepted in final form August 5, 2009.

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Predicting treatment responses to IV immunoglobulins: Can we already ask the genes?

Helmar C. Lehmann and Bernd C. Kieseier
Neurology 2009 73: 1344-1345. [Full Text] [PDF]

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				H. C. Lehmann and B. C. Kieseier Predicting treatment responses to IV immunoglobulins: Can we already ask the genes? Neurology, October 27, 2009; 73(17): 1344 - 1345. [Full Text] [PDF]