Sequential changes in oligoclonal patterns during the course of multiple sclerosis.

Thompson, E J; Kaufmann, Peter; Rudge, Peter

doi:10.1136/jnnp.46.2.115

Cited by 20 publications

(9 citation statements)

References 11 publications

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“…Matching transcriptome and proteome in the CSF has shown that cells present in the cerebrospinal fluid (CSF) are of the same clonal origin as the OKB producing cells [10]. The OCB in the CSF of MS patients persist for many years [11,12], although changes of the banding pattern have been observed longitudinally in some patients [12]. The tendency of the OCB to persist suggests that the CNS provides a long-term survival niche for plasma cells.…”

Section: The Cns Of Ms Patients Provides a B Cell Fostering Environmentmentioning

confidence: 97%

See 1 more Smart Citation

Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

Meinl¹,

Krumbholz²,

Derfuss³

et al. 2008

Journal of the Neurological Sciences

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Section: The Cns Of Ms Patients Provides a B Cell Fostering Environmentmentioning

confidence: 97%

“…The tendency of the OCB to persist suggests that the CNS provides a long-term survival niche for plasma cells. The changes of the banding pattern [12] might indicate that the plasma cells compete for the limited survival niches.…”

Section: The Cns Of Ms Patients Provides a B Cell Fostering Environmentmentioning

confidence: 99%

Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

Meinl¹,

Krumbholz²,

Derfuss³

et al. 2008

Journal of the Neurological Sciences

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“…The OCBs in the CSF of MS patients remain for many years,69, 70 although changes of the banding pattern have been observed longitudinally in some patients 70. The tendency of the OCBs to persist suggests that the CNS provides a long‐term survival niche for plasma cells (see Fig 2).…”

Section: Features Of Intrathecally Produced Iggmentioning

confidence: 99%

“…The tendency of the OCBs to persist suggests that the CNS provides a long‐term survival niche for plasma cells (see Fig 2). The changes of the banding pattern70 might indicate that the plasma cells compete for the limited survival niches. It is not known whether the presumed, long‐lived plasma cells that cause the persisting OCBs in MS originate from tracks 1, 2, 3, or 4 (see Fig 1).…”

Section: Features Of Intrathecally Produced Iggmentioning

confidence: 99%

B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production, and therapeutic modulation

Meinl

Krumbholz

Hohlfeld

2006

Annals of Neurology

284

180

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B cells have long played an enigmatic role in the scenario of multiple sclerosis pathogenesis. This review summarizes recent progress in our understanding of B-cell trafficking, survival, and differentiation in the central nervous system (CNS). We propose four possible routes of intrathecal immunoglobulin-producing cells. The inflammatory CNS provides a unique, B-cell-friendly environment, in which B lineage cells, notably long-lived plasma cells, can survive for many years, perhaps even for a lifetime. These new findings offer a plausible explanation for the notorious persistence and stability of cerebrospinal fluid oligoclonal bands. Furthermore, we highlight similarities and differences of intrathecal immunoglobulin production in multiple sclerosis patients and patients with other CNS inflammatory conditions. Finally, we outline the possibly double-edged effects of B cells and immunoglobulin in the CNS and discuss various therapeutic strategies for targeting the B-cell response.

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“…Oligoklonal bantların MS olgularının BOS örneklerinde yıllarca varlıklarını sürdürebilmeleri bu bantları oluşturan Ig'lerin MSS'de bulunan uzun yaşam süreli plazma hücreleri tarafından üretildiğini ve MS MSS'de bu plazma hücrelerinin varlıklarını sürdürebilecekleri uygun ortamın bulunduğunu göstermektedir (24). Yıllarca yaşamlarını sürdürerek antikor üretebilen uzun yaşamlı plazma hücrelerinin gelişmesini sağlayan faktörlerden başlıcaları, her biri inflamasyonlu MSS dokusunda yüksek miktarda bulunan, CXCL12, IL-6, TNF-α, α4β1 integrin ve BAFF ("B-cell-activating factor of the TNF family")'dır (13,14).…”

Section: Mss'de Ig Birikimleriunclassified

Multipl Skleroz Patogenezinde B Hücrelerinin Rolü ve B Hücre Karşıtı Monoklonal Antikor Tedavileri

Tüzün¹

2011

Npa

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Ya z›fl ma Ad re si/Ad dress for Cor res pon den ce: Dr. Erdem Tüzün, İstanbul Üniversitesi İstanbul Tıp Fakültesi, Nöroloji Anabilim Dalı, İstanbul, Türkiye Tel.: +90 212 414 20 00/32580 E-pos ta: drerdem@yahoo.com © Nö rop si ki yat ri Ar şi vi Der gi si, Ga le nos Ya yı ne vi ta ra f›n dan ba s›l m›fl t›r. / © Arc hi ves of Neu ropsy chi atry, pub lis hed by Ga le nos Pub lis hing. ABS TRACTThe presence of B cells, plasma cells and increased immunoglobulin (Ig) levels in multiple sclerosis (MS) lesions and cerebrospinal fluid (CSF) samples has suggested that the humoral immunity plays an important role in MS pathogenesis. Moreover, the demonstration of correlation of CSF B lymphocyte and Ig levels with the clinical course and prognosis of the disease has substantiated this notion. However, until the advent of clinical trials performed with B cell-targeting monoclonal antibodies, the role of B lymphocytes in MS pathogenesis has been a matter of controversy. Clinical trials testing the chimeric anti-CD20 monoclonal antibody rituximab and other monoclonal antibodies have shown that B-cell depletion significantly decreases MS relapse rate, disability progression and development of new contrast-enhancing MRI lesions. With the introduction of novel antibodies and fusion proteins that are currently being produced and tested, treatment methods with higher efficacy and lower side-effect profile are expected to be developed in the forthcoming years. (Archives of Neuropsychiatry 2011; 48 Supplement 2: 73-8) ÖZET Multipl skleroz (MS) lezyonlarında ve beyin-omurilik sıvısı (BOS) örneklerinde saptanan B hücresi, plazma hücresi ve artmış immunglobulin (Ig) düzeyleri MS patogenezinde hümoral immünitenin önemli rol oynadığını düşündürmektedir. Ayrıca BOS B lenfosit ve Ig düzeyleri ile hastalığın klinik seyri ve prognozu arasında korelasyon olduğunun gösterilmesi bu görüşü desteklemiştir. Ancak B hücrelerini hedefleyen monoklonal antikorlarla yapılan klinik çalışmalara kadar B lenfositlerinin MS patogenezindeki rolüne şüpheyle yaklaşılmıştır. Başta kimerik anti-CD20 monoklonal antikoru rituksimab olmak üzere çeşitli monoklonal antikorlarla yapılan klinik çalışmalar, B hücre tüketiminin, MS olgularının atak sıklığını, özürlülük gelişimini ve kontrast tutan yeni MR lezyonu oluşumunu belirgin derece azalttığını göstermiştir. Geliştirilmekte ve denenmekte olan yeni antikor ve füzyon proteinleri ile önümüzdeki yıllarda daha etkin ve daha düşük yan etki profilli tedavi yöntemlerinin geliştirilmesi beklenmektedir. (Nöropsikiyatri Arşivi 2011; 48 Özel Say› 2: 73-8) Anah tar ke li me ler: B hücreleri, multipl skleroz, monoklonal antikor, anti-CD20, tedavi, otoimmünite

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Sequential changes in oligoclonal patterns during the course of multiple sclerosis.

Cited by 20 publications

References 11 publications

Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

Compartmentalization of inflammation in the CNS: A major mechanism driving progressive multiple sclerosis

B lineage cells in the inflammatory central nervous system environment: Migration, maintenance, local antibody production, and therapeutic modulation

Multipl Skleroz Patogenezinde B Hücrelerinin Rolü ve B Hücre Karşıtı Monoklonal Antikor Tedavileri

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