Intrathecal activation of the complement system and disability in multiple sclerosis

Sellebjerg, Finn; Jaliashvili, Irakli; Christiansen, Michael; Garred, Peter

doi:10.1016/s0022-510x(98)00086-0

Cited by 74 publications

(51 citation statements)

References 33 publications

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“…Another possibility is that B cells entering the CNS secrete complement-binding Abs which lead to local activation of complement proteins including C5a and C3a. C5a is an especially potent chemo-attractant for monocytes, macrophages and neutrophils, and also upregulates the production of several chemokines by endothelial cells (Sellebjerg et al, 1998;Guo and Ward, 2005).…”

Section: Discussionmentioning

confidence: 99%

Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients

Cross

Stark

Lauber

et al. 2006

Journal of Neuroimmunology

407

314

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Effects of B cell depletion by rituximab, a monoclonal antibody to CD20, were studied in patients with relapsing MS that had not responded optimally to standard immunomodulatory therapies. Flow cytometry demonstrated reduced cerebrospinal fluid (CSF) B cells and T cells in most patients at 6 months post-treatment. ELISAs demonstrated modest reductions in serum antibodies to myelin oligodendrocyte glycoprotein and myelin basic protein in some subjects. Beta-interferon neutralizing antibodies were reduced in three subjects, but developed anew after treatment in three others, suggesting caution in considering rituximab as a means to eliminate NABs. In summary, rituximab depleted B cells from CSF at 24 weeks after initial treatment, and this B cell depletion was associated with a reduction in CSF T cells as well.

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Section: Discussionmentioning

confidence: 99%

Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients

Cross

Stark

Lauber

et al. 2006

Journal of Neuroimmunology

407

314

View full text Add to dashboard Cite

show abstract

“…these antibodies cause sickness through three principal mechanisms: opsonization and phagocytosis, antibody dependent cellular cytoxicity and injuries mediated by the complement system. this triggers the lysis through the formation of a membrane attack complex (MAc), the attraction of the macrophages (chymiotaxis) that liberate toxic substances, develop inflammatory responses and opsonization with the consequent phagocytosis [15][16][17] .…”

mentioning

confidence: 99%

C3c intrathecal synthesis evaluation in patients with multiple sclerosis

Padilla-Docal¹,

Dorta‐Contreras²,

Fundora-Hernández³

et al. 2007

Arq. Neuro-Psiquiatr.

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-Introduction: Multiple sclerosis (Ms) is a chronic, inflammatory and progressive disease of the central nervous system in which local inflammatory injuries of the brain white matter appears, being the most outstanding feature the myeline loss (demyelination). Objective: to determine if the complement system might be involved in the Ms immunopathogeny favouring the mechanism intervening in the myelin destruction. Method: samples of sera and csF from twelve patients with a diagnosis of Ms obtained at the moment of the admission to the hospital at the beginning of the break out, were collected. Levels of c3c and albumin in sera and in csF were quantified using radial immunodiffusion plates. Results: High values over 80% of intrathecal synthesis were obtained except in one of the patients. Conclusion: Intrathecal synthesis of c3c and its liberation to the csF means that the activation of the complement system in any of the two ways has taken place, and that once performed its biological functions, has suffered a degradation process Key words: cytotoxicity, complement, multiple sclerosis, hypersensibility, immunopathogenicity, reibergram.evaluación de la síntesis intratecal de C3c en pacientes con esclerosis múltiple resuMeN -Introducción: La esclerosis múltiple (eM) es una enfermedad crónica, inflamatoria y progresiva del sistema nervioso central que cursa con la aparición de lesiones inflamatorias focales en la sustancia blanca cerebral, en las que lo más llamativo es la pérdida de mielina (desmielinización). Objetivo: conocer si el sistema de complemento puede estar involucrado en la inmunopatogenia de la eM favoreciendo los mecanismos que median la destrucción de la mielina. Método: se colectaron muestras de suero y Lcr de doce pacientes con diagnóstico de eM obtenidas en el momento del ingreso al inicio del brote. se cuantificaron los niveles de c3c y albúmina en suero y en Lcr en placas de inmunodifusión radial. Resultados: se obtuvieron altos valores que superan el 80% de síntesis intratecal, menos en uno de los pacientes. Conclusion: La síntesis intratecal de c3c y su liberación al Lcr significa que ha sucedido la activación del sistema de complemento en alguna de las dos vías y que una vez cumplidas sus funciones biológicas, ha sufrido un proceso de degradación y liberación al Lcr en forma de c3c.PALABrAs-cLAve: citotoxicidad, complemento, esclerosis múltiple, hipersensibilidad, inmunopatogenia, reibergrama.

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“…[1][2][3][4][5] Deposition of complement-activation products has been shown in Alzheimer's disease, 6,7 ischemia/reperfusion injury, 8 Huntington's and Prion disease, 9,10 and multiple sclerosis (MS). [11][12][13][14][15] In the immune-mediated inflammatory demyelinating disease, multiple sclerosis, and its animal model, experimental autoimmune encephalomyelitis (EAE), myelin, and oligodendrocytes are primary targets of damage.…”

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confidence: 99%

Complement C5 in Experimental Autoimmune Encephalomyelitis (EAE) Facilitates Remyelination and Prevents Gliosis

Weerth¹,

Rus²,

Shin³

et al. 2003

The American Journal of Pathology

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Activation of the classical complement system is known to play a central role in autoimmune demyelination. We have analyzed the role of complement component C5 in experimental autoimmune encephalomyelitis (EAE) using C5-deficient (C5-d) and C5-sufficient (C5-s) mice. Both groups of mice displayed early onset EAE, a short recovery phase, and similar stable chronic courses. However, in contrast to the clinical similarities, marked differences were apparent by histopathology. During acute EAE in C5-d, a delay in inflammatory cell infiltration and tissue damage was observed along with restricted lesion areas, which in C5-s mice were more extensive and diffuse. More striking were the differences in chronic lesions. In C5-d mice, inflammatory demyelination and Wallerian degeneration were followed by axonal depletion and severe gliosis, while in C5-s, the same initial signs were followed by axonal sparing and extensive remyelination. In C5-d, immunohistochemistry and Western blotting showed an increase in glial fibrillary acidic protein and a decrease in neurofilament protein, proteolipid protein, and several pro-inflammatory markers. These results in the EAE model indicate that absence of C5 resulted in fiber loss and extensive scarring, whereas presence of C5-favored axonal survival and more efficient remyelination.

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Intrathecal activation of the complement system and disability in multiple sclerosis

Cited by 74 publications

References 33 publications

Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients

Rituximab reduces B cells and T cells in cerebrospinal fluid of multiple sclerosis patients

C3c intrathecal synthesis evaluation in patients with multiple sclerosis

Complement C5 in Experimental Autoimmune Encephalomyelitis (EAE) Facilitates Remyelination and Prevents Gliosis

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