Recent advances of multiple sclerosis research in Japan

研究成果: ジャーナルへの寄稿評論記事

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抄録

Multiple sclerosis (MS) is rare in Asians, but selective and severe involvement of the optic nerve and spinal cord is characteristic when it does occur. Recent epidemiological studies have demonstrated an increase in the prevalence of MS in Japan. Moreover, while there are two distinct phenotypes of MS in Asians, opticospinal (OSMS) and conventional (CMS), it is important to determine if MS phenotypes in Japanese are presently undergoing change. Four nationwide surveys of MS have been conducted in Japan: 1972, 1982, 1989, and 2004. The most recent survey demonstrated: (1) a four-fold increase in the estimated number of clinically definite MS patients in 2003 (9,900; crude MS prevalence, 7.7/100,000) compared to the numbers in 1972; (2) a shift in the peak age at onset from the early 30s in 1989 to the early 20s in 2003; (3) a successive proportional decrease in optic-spinal involvement; (4) a significant north-south gradient for the CMS/OSMS ratio; (5) after dividing the mainland (3045° North) into northern and southern parts at 37°N, northern-born northern-residents (northern patients) showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern-residents; (6) among northern patients, the absolute numbers of CMS patients and those with Barkhof brain lesions rapidly increased with advancing birth year; (7) further classifications based on MRI findings demonstrated distinct demographic features with not only the CMS/OSMS phenotype but also the presence or absence of longitudinally extensive spinal cord lesions (LESCLs). In northern patients, the incidence of OSMS with LESCLs had decreased with advancing year of birth, while incidences of intermediate phenotypes, such as CMS with LESCLs and OSMS without LESCLs, had increased. Although phenotypic changes appeared to be mostly attributable to the increase in CMS patients with Barkhof brain lesions in younger northern populations, the emergence of such intermediate phenotypes may support the notion that CMS and OSMS represent opposite ends of a single spectrum of disease. These findings suggest that phenotype is drastically altered by environmental factors, such as latitude and " Westernization". The recent discovery of a specific IgG against neuromyelitis optica (NMO) suggests that NMO is a disease entity distinct from MS. NMO-IgG targeting aquaporin-4 (AQP4) is present in 30 to 60% of Japanese OSMS patients with LESCLs. MS patients with anti-AQP4 antibodies were not responsive to interferon beta-lb while those without anti-AQP4 antibody did respond. In CSF, IL-17, IFN-gamma, granulocyte-colony stimulating factor, and IL-8 were markedly upregulated in OSMS patients, irrespective of the presence or absence of the anti-AQP4 antibody. Pathological studies of autopsy specimens of OSMS patients disclose that there are two subtypes of OSMS, with or without showing a selective AQP4 loss; although both subtypes had severe necrotic spinal cord lesions. There are also OSMS cases showing both pathological patterns at different lesions. These findings indicate that both anti-AQP4 autoimmunity-related and -unrelated OSMS occur in Japanese. Th17/Th1 cells are involved in both conditions, while additional humoral factors also act in the former.

元の言語英語
ページ(範囲)549-559
ページ数11
ジャーナルClinical Neurology
49
発行部数9
DOI
出版物ステータス出版済み - 1 1 2009

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Multiple Sclerosis
Aquaporin 4
Japan
Spinal Cord
Research
Neuromyelitis Optica
Phenotype
Brain
Antibodies
Immunoglobulin G
Parturition
Th17 Cells
Th1 Cells
Interleukin-17
Interferon-beta
Incidence
Granulocyte Colony-Stimulating Factor
Optic Nerve
Autoimmunity
Interleukin-8

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

これを引用

Recent advances of multiple sclerosis research in Japan. / Kira, Jun-Ichi.

:: Clinical Neurology, 巻 49, 番号 9, 01.01.2009, p. 549-559.

研究成果: ジャーナルへの寄稿評論記事

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title = "Recent advances of multiple sclerosis research in Japan",
abstract = "Multiple sclerosis (MS) is rare in Asians, but selective and severe involvement of the optic nerve and spinal cord is characteristic when it does occur. Recent epidemiological studies have demonstrated an increase in the prevalence of MS in Japan. Moreover, while there are two distinct phenotypes of MS in Asians, opticospinal (OSMS) and conventional (CMS), it is important to determine if MS phenotypes in Japanese are presently undergoing change. Four nationwide surveys of MS have been conducted in Japan: 1972, 1982, 1989, and 2004. The most recent survey demonstrated: (1) a four-fold increase in the estimated number of clinically definite MS patients in 2003 (9,900; crude MS prevalence, 7.7/100,000) compared to the numbers in 1972; (2) a shift in the peak age at onset from the early 30s in 1989 to the early 20s in 2003; (3) a successive proportional decrease in optic-spinal involvement; (4) a significant north-south gradient for the CMS/OSMS ratio; (5) after dividing the mainland (3045° North) into northern and southern parts at 37°N, northern-born northern-residents (northern patients) showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern-residents; (6) among northern patients, the absolute numbers of CMS patients and those with Barkhof brain lesions rapidly increased with advancing birth year; (7) further classifications based on MRI findings demonstrated distinct demographic features with not only the CMS/OSMS phenotype but also the presence or absence of longitudinally extensive spinal cord lesions (LESCLs). In northern patients, the incidence of OSMS with LESCLs had decreased with advancing year of birth, while incidences of intermediate phenotypes, such as CMS with LESCLs and OSMS without LESCLs, had increased. Although phenotypic changes appeared to be mostly attributable to the increase in CMS patients with Barkhof brain lesions in younger northern populations, the emergence of such intermediate phenotypes may support the notion that CMS and OSMS represent opposite ends of a single spectrum of disease. These findings suggest that phenotype is drastically altered by environmental factors, such as latitude and {"} Westernization{"}. The recent discovery of a specific IgG against neuromyelitis optica (NMO) suggests that NMO is a disease entity distinct from MS. NMO-IgG targeting aquaporin-4 (AQP4) is present in 30 to 60{\%} of Japanese OSMS patients with LESCLs. MS patients with anti-AQP4 antibodies were not responsive to interferon beta-lb while those without anti-AQP4 antibody did respond. In CSF, IL-17, IFN-gamma, granulocyte-colony stimulating factor, and IL-8 were markedly upregulated in OSMS patients, irrespective of the presence or absence of the anti-AQP4 antibody. Pathological studies of autopsy specimens of OSMS patients disclose that there are two subtypes of OSMS, with or without showing a selective AQP4 loss; although both subtypes had severe necrotic spinal cord lesions. There are also OSMS cases showing both pathological patterns at different lesions. These findings indicate that both anti-AQP4 autoimmunity-related and -unrelated OSMS occur in Japanese. Th17/Th1 cells are involved in both conditions, while additional humoral factors also act in the former.",
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N2 - Multiple sclerosis (MS) is rare in Asians, but selective and severe involvement of the optic nerve and spinal cord is characteristic when it does occur. Recent epidemiological studies have demonstrated an increase in the prevalence of MS in Japan. Moreover, while there are two distinct phenotypes of MS in Asians, opticospinal (OSMS) and conventional (CMS), it is important to determine if MS phenotypes in Japanese are presently undergoing change. Four nationwide surveys of MS have been conducted in Japan: 1972, 1982, 1989, and 2004. The most recent survey demonstrated: (1) a four-fold increase in the estimated number of clinically definite MS patients in 2003 (9,900; crude MS prevalence, 7.7/100,000) compared to the numbers in 1972; (2) a shift in the peak age at onset from the early 30s in 1989 to the early 20s in 2003; (3) a successive proportional decrease in optic-spinal involvement; (4) a significant north-south gradient for the CMS/OSMS ratio; (5) after dividing the mainland (3045° North) into northern and southern parts at 37°N, northern-born northern-residents (northern patients) showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern-residents; (6) among northern patients, the absolute numbers of CMS patients and those with Barkhof brain lesions rapidly increased with advancing birth year; (7) further classifications based on MRI findings demonstrated distinct demographic features with not only the CMS/OSMS phenotype but also the presence or absence of longitudinally extensive spinal cord lesions (LESCLs). In northern patients, the incidence of OSMS with LESCLs had decreased with advancing year of birth, while incidences of intermediate phenotypes, such as CMS with LESCLs and OSMS without LESCLs, had increased. Although phenotypic changes appeared to be mostly attributable to the increase in CMS patients with Barkhof brain lesions in younger northern populations, the emergence of such intermediate phenotypes may support the notion that CMS and OSMS represent opposite ends of a single spectrum of disease. These findings suggest that phenotype is drastically altered by environmental factors, such as latitude and " Westernization". The recent discovery of a specific IgG against neuromyelitis optica (NMO) suggests that NMO is a disease entity distinct from MS. NMO-IgG targeting aquaporin-4 (AQP4) is present in 30 to 60% of Japanese OSMS patients with LESCLs. MS patients with anti-AQP4 antibodies were not responsive to interferon beta-lb while those without anti-AQP4 antibody did respond. In CSF, IL-17, IFN-gamma, granulocyte-colony stimulating factor, and IL-8 were markedly upregulated in OSMS patients, irrespective of the presence or absence of the anti-AQP4 antibody. Pathological studies of autopsy specimens of OSMS patients disclose that there are two subtypes of OSMS, with or without showing a selective AQP4 loss; although both subtypes had severe necrotic spinal cord lesions. There are also OSMS cases showing both pathological patterns at different lesions. These findings indicate that both anti-AQP4 autoimmunity-related and -unrelated OSMS occur in Japanese. Th17/Th1 cells are involved in both conditions, while additional humoral factors also act in the former.

AB - Multiple sclerosis (MS) is rare in Asians, but selective and severe involvement of the optic nerve and spinal cord is characteristic when it does occur. Recent epidemiological studies have demonstrated an increase in the prevalence of MS in Japan. Moreover, while there are two distinct phenotypes of MS in Asians, opticospinal (OSMS) and conventional (CMS), it is important to determine if MS phenotypes in Japanese are presently undergoing change. Four nationwide surveys of MS have been conducted in Japan: 1972, 1982, 1989, and 2004. The most recent survey demonstrated: (1) a four-fold increase in the estimated number of clinically definite MS patients in 2003 (9,900; crude MS prevalence, 7.7/100,000) compared to the numbers in 1972; (2) a shift in the peak age at onset from the early 30s in 1989 to the early 20s in 2003; (3) a successive proportional decrease in optic-spinal involvement; (4) a significant north-south gradient for the CMS/OSMS ratio; (5) after dividing the mainland (3045° North) into northern and southern parts at 37°N, northern-born northern-residents (northern patients) showed a significantly higher CMS/OSMS ratio and higher frequency of brain lesions fulfilling the Barkhof criteria (Barkhof brain lesions) than southern-born southern-residents; (6) among northern patients, the absolute numbers of CMS patients and those with Barkhof brain lesions rapidly increased with advancing birth year; (7) further classifications based on MRI findings demonstrated distinct demographic features with not only the CMS/OSMS phenotype but also the presence or absence of longitudinally extensive spinal cord lesions (LESCLs). In northern patients, the incidence of OSMS with LESCLs had decreased with advancing year of birth, while incidences of intermediate phenotypes, such as CMS with LESCLs and OSMS without LESCLs, had increased. Although phenotypic changes appeared to be mostly attributable to the increase in CMS patients with Barkhof brain lesions in younger northern populations, the emergence of such intermediate phenotypes may support the notion that CMS and OSMS represent opposite ends of a single spectrum of disease. These findings suggest that phenotype is drastically altered by environmental factors, such as latitude and " Westernization". The recent discovery of a specific IgG against neuromyelitis optica (NMO) suggests that NMO is a disease entity distinct from MS. NMO-IgG targeting aquaporin-4 (AQP4) is present in 30 to 60% of Japanese OSMS patients with LESCLs. MS patients with anti-AQP4 antibodies were not responsive to interferon beta-lb while those without anti-AQP4 antibody did respond. In CSF, IL-17, IFN-gamma, granulocyte-colony stimulating factor, and IL-8 were markedly upregulated in OSMS patients, irrespective of the presence or absence of the anti-AQP4 antibody. Pathological studies of autopsy specimens of OSMS patients disclose that there are two subtypes of OSMS, with or without showing a selective AQP4 loss; although both subtypes had severe necrotic spinal cord lesions. There are also OSMS cases showing both pathological patterns at different lesions. These findings indicate that both anti-AQP4 autoimmunity-related and -unrelated OSMS occur in Japanese. Th17/Th1 cells are involved in both conditions, while additional humoral factors also act in the former.

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