الفهرس 
Definition of Monoclonal antibody
Multiple sclerosisOnly 14 pages are availabe for public view
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Abstract
Monoclonal antibodies have a role in pathogenesis, diagnosis and treatment of different neurological disorders.
Multiple sclerosis: The pathologic hallmark of the disease is inflammation mediated by T cell that triggers inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies.
The CSF is tested for OCB, which are an inflammation marker found in 75–85% of people with MS; also there are antimyelines antibodies such as those directed against MBP, PLP and MOG have been variably reported in the serum as well as CSF of patients with MS.
Treatment strategies have changed from unspecific to specific therapies thanks to the development of mAb that target specific antigens responsible for selective effects. Natalizumab was the first mAb to be FDA approved for treatment of patients with MS.
Natalizumab is a humanized Ab directed against α 4 1 integrin, a molecule believed to play a role in allowing the entry of inflammatory cells into the central nervous system. This therapy seemed promising because it reduced disability rates and magnetic resonance imaging evidence of disease.
Besides natalizumab mentioned above, three more mAbs are expected to have the potential to considerably improve MS therapy: alemtuzumab, daclizumab and rituximab. Furthermore, a mAb directed against CD28, a costimulatory receptor for CD4 T-cells, has been tested. Experiments with this mAb showed that promising results in rodents could not simply be translated into humans.
Neuromyelitis optica: is an inflammatory demyelinating condition that attacks the optic nerve and spinal cord. The Ab against aquaporin 4 used as sensitive diagnostic test for NMO. Rituximab lead to Ab suppression so could help decrease central nervous system damage and lead to decreased attack frequency and used as treatment for NMO.
Myasthenia gravis: autoimmune neuromuscular disease leading to fluctuating muscle weakness and fatigability. In which weakness is caused by circulating antibodies that block acetylcholine receptors at the post-synaptic neuromuscular junction.
Anti-AChR antibody test considered as gold standard test. These antibodies are found in nearly 80%–85% of patients with generalized myasthenia gravis and 50%–60% cases of ocular myasthenia gravis. And about 10%–20% of patients do not have anti-AChR antibodies in their sera. However; they have antibody attack MuSK. And other antibodies as antititin, anti-Kv1.4.
Rituximab, a monoclonal antibody against CD20+ cells that causes prolonged B cell depletion. Treatment with rituximab leads to a sustained clinical improvement and discontinuation or reduction of prednisolone and other drugs. Therapy with rituximab was guided by the total count of peripheral B lymphocytes. Reviewing the anecdotal literature on rituximab for MG, we conclude that preliminary data on the efficacy and safety of rituximab are encouraging and that further studies in MG seem warranted.
Inclusion body myositis: is an inflammatory muscle disease with evidence for an autoimmune basis and evidence for a degenerative process.
Alemtuzumab is a humanized monoclonal antibody that causes an immediate depletion or severe reduction of peripheral blood lymphocytes, lasting at least 6 months. Alemtuzumab infusions in sIBM patients deplete endomysial T cells and alter the natural course of the disease.
New biologic agents targeting the main immuno pathological processes. such as T-cell proliferation, transmigration, antigen recognition or ER stress, might produce more rewarding results. Such therapies might be accomplished using the available monoclonal antibodies directed against T-cell regulatory pathways, such as CD56, costimulatory molecules (CD28/CTLA4), adhesion molecules (integrins/LFA-1/ICAM), cytokines (TNF-α), chemokines or B cells (CD20) .
Chronic inflammatory demyelinating polyradiculoneuropathy and other neuropathies: The pathogenesis of CIDP is inflammation in peripheral nerves and nerve roots due to immune response mediated by T cells and circulating antibodies directed against a self antigen confined to peripheral nervous system proteins.
Antibodies against several neural antigens have been associated with a number of chronic immune-mediated neuropathies. Including antibodies to MAG which have been associated with predominantly sensory demyelinating neuropathy associated with IgM monoclonal gammopathy. antibodies to sulfatide, associated with a predominantly sensory axonal neuropathy or demyelinating, antibodies to the gangliosides GM1, GM2 or GD1a associated with multifocal motor neuropathy with or without conduction block and to GQ1b and GD1b associated with sensory PN+IgM.
Rituximab, used to treat diseases characterized by having a plethora of B cells, overactive B cells, or dysfunctional B cells. It is currently used in the treatment of some autoimmune disorders as dysimmune neuropathies with IgM antibodies to (MAG) or to GM1 ganglioside by depleting B lymphocytes as also by reducing titers of serum autoantibodies.
Alemtuzumab, a recombinant DNA derived humanized MAb directed against the 21–28 kDa cell surface glycoprotein, CD52 Considering that increased levels of circulating activated peripheral T lymphocytes are implicated in the pathogenesis of CIDP, and data also shows that MAbs directed against CD52 cause complement mediated lysis and reduce the numbers of circulating lymphocytes.
Cerebrovascular stroke: Abciximab has been evaluated in patients with AIS. The only group where it may be potentially effective is, during neuroendovascular procedures, when the incidence of thromboembolic complications reduces after using abciximab.
A summary of studies using tirofiban in AIS is presented in Tirofiban appears to improve outcomes in acute stroke, without causing any increase in bleeding complications. Further trial of tirofiban is ongoing.
Paraneoplastic disorders: May result from production and release of antibodies and physiologically active substances that attack normal tissues leading to tissue damage. In the nervous system, the response occurs when cancer-fighting antibodies or blood T cells mistakenly attack normal nervous cells.
Demonstration of these autoantibodies is very important to confirm the diagnosis of a paraneoplastic syndrome. Such as Anti-Hu detected in the serum of patients with paraneoplastic subacute sensory neuronopathy and/or encephalomyelitis, Anti-Ri in patients with opsoclonus/myoclonus syndrome, Antibodies directed against amphiphysin have been detected in the serum of patients with the paraneoplastic form of stiff man syndrome and anti-Yo or anti-Purkinje cell antibody 1 (APCA-1) in patients with paraneoplastic cerebellar degeneration.
Rituximab has been reported in open-label studies in a variety of other antibody associated autoimmune disorders including polyneuropathy associated with IgM antibodies.
We found that rituximab induced elimination of circulating B lymphocytes in patients with newly diagnosed anti-Hu and anti-Yo associated PNS would result in the prevention of the development of antibody secreting cells, in a reduction of autoantibody titers and in clinical improvement or stabilization.
Cryoglobulinemic Vasculitis: Rituximab was effective on skin vasculitis manifestations, low-grade B-cell lymphoma, arthralgias, and fever, and also provided significant relief from subjective symptoms of peripheral neuropathy.
Rituximab also was effective in a patient with chronic ataxic neuropathy with cold agglutinins and in another patient with severe polyneuropathy secondary to cryoglobulinemia type III.
POEMS syndrome: Bevacizumab targeting VEGF within the context of POEMS syndrome has been assessed only in single case reports. There are two case reports of POEMS patients with increased VEGF levels in which the administration of Bevacizumab resulted in a rapid decrease of VEGF levels and significant improvement of peripheral nerve function (Badros et al, 2005).
Central nervous system lymphoma: Rituximab and temozolomide combination has efficacy against CNS lymphomas and this immunochemotherapy combination has acceptable toxicity.
Radioimmunotherapy with yttrium-90 (90Y) ibritummomab tiuxetan or iodine-131 (131I) tositumomab. Which are murine mAbs against CD20 antigen that are conjugated to a radioactive source, they have proven efficacy for relapsed or refractory non-Hodgkin’s lymphomas.
Epratuzumab, a humanized mouse anti-CD22 mAb, has shown efficacy against indolent and aggressive non-Hodgkin’s lymphomas. Its efficacy may be improved with concomitant cytotoxic chemotherapies, such as temozolomide.
Alemtuzumab is a humanized mAb against CD52 antigen on B- and T-lymphoma cells, so used in treatment of chronic lymphocytic leukemia. And Natalizumab used to stop the trafficking of B-lymphoma cells from systemic circulation into the CNS and block the invasive behavior of primary CNS lymphomas in the brain