Oligoclonal bands and antibody responses in Multiple Sclerosis

Abstract

Multiple Sclerosis (MS) is an inflammatory disease of the Central Nervous System with multifocal areas of demyelination. Although its etiology and pathogenesis remain controversial, several lines of evidence indicate that MS is mediated by a misdirected immune response against one or several myelin proteins. The involvement of diverse leukocyte subsets and their products in MS is still the subject of considerable debate. The emphasis on T cells has derived mainly from the detection of activated T cells in MS plaques and analogies with animal models of MS. Because of these observations cell-mediated immunity has dominated the research field of MS to this day. However, in recent years the role of B cells, plasma cells and immunoglobulins in MS have been re-examined, and current findings indicate that humoral immunity also plays a major role in disease pathogenesis. B cells and their products could exert several potential effects during the course of MS. Firstly, autoantibodies against specific myelin antigens could mediate damage to myelin membranes. Secondly, some studies suggest that natural autoantibodies could enhance remyelination. Thirdly, antibodies directed against myelin components can participate in anti-idiotypic networks, which may regulate the course of MS. Increased intrathecal immunoglobulin synthesis reflected by raised IgG indices and an oligoclonal pattern is the most common abnormality detected in MS patients. The introduction of more sensitive procedures for protein detection has allowed demonstrating oligoclonal bands (OCBs) in up to 95 % of patients with clinically definite MS. Although the presence of OCBs in CSF of MS patients is now well established as a sensitive laboratory test to support the clinical diagnosis, OCBs may be present in other disorders, including those not directly related to infection or abnormal immune response. Nevertheless, the pathogenesis of OCBs in MS is still obscure, and despite extensive research their antigenic target(s) have yet to be established. Therefore, a critical task is to identify the specificity of such target(s), thus providing significant clues about MS etiology. For this purpose, novel molecular immunologic strategies have been recently developed to offer alternative approaches to identify putative antigens recognized by antibodies present in MS patients. The elucidation of the mechanisms and target(s) responsible for the onset of MS has obvious implications for the further development of specific therapies.

Study of oligoclonal bands restricted to the cerebrospinal fluid in multiple sclerosis patients in the city of São Paulo

“…This information may be helpful for distinction when images seen at MRI may correspond to acute lesions or only to cicatricial demyelination; (4) the graphic representation of samples from patients with IgG immunoproduction is displayed in a similar way to that of the Link's IgG index analysis (region 4 of Fig 2). Although CSF analysis in MS aims to characterize the local immune response in the CNS, a number of other features may differentiate MS from other diseases of the CNS, such as: (1) in MS, there is usually a high number of OCB; (2) in MS, the simultaneous presence of OCB in CSF and in the blood serum is uncommon, even if a high number of bands have been identified in the CSF; (3) there usually is a normal number of cell count or a slight pleocytosis, usually below 30 cells/mm 3 , with an absolute predominance of lymphomononuclear cells; (4) the total protein content is usually normal or slightly above normal, generally below 70 mg/dL; (5) the concentration of glucose should be within reference limits [2][3][4]20 .…”

Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen

“…A poor understanding of the etiology of MS has complicated the development of effective therapeutics (2). Despite strong evidence for the contribution of T cell responses to manifestations of autoimmunity in the central nervous system (CNS) of patients with MS (3,4), recent findings encouraged investigators to search also for B cell-mediated contributions to the MS pathogenesis (5,6).…”

Determinação de autoanticorpos para antígenos da mielina no soro de pacientes HLA - DQB1*0602 com esclerose múltipla

“…A etiopatogenia da EM ainda é desconhecida embora um distúrbio ou processo infeccioso sistêmico contribua para o desencadeamento de inflamação recorrente de natureza autoimune com lesões desmielinizantes no SNC 1,2,4,10 . A inflamação em diferentes regiões do cérebro e a heterogeneidade das manifestações clínicas nos pacientes EM parece ser influenciada pela especificidade do reconhecimento antigênico dos linfócitos T ativados que migram para o SNC e também por mecanismos efetores dependentes de autoanticorpos 1,10,21 .…”

“…A inflamação em diferentes regiões do cérebro e a heterogeneidade das manifestações clínicas nos pacientes EM parece ser influenciada pela especificidade do reconhecimento antigênico dos linfócitos T ativados que migram para o SNC e também por mecanismos efetores dependentes de autoanticorpos 1,10,21 . Outro aspecto importante da participação dos linfócitos B na desmielinização refere-se à sua capacidade de funcionar como célula acessória na apresentação de antígenos solú-veis durante a resposta imune inicial.…”

“…Contudo, a deposição de imunoglobulinas e componentes da ativação do sistema complemento próximo da lesão inflamatória sugere participação importante dos linfócitos B na fisiopatologia da lesão no SNC 9,10 . A proteína básica da mielina (MBP), o proteolipídeo (PLP) e a sequência MOG 92-106 da glicoproteína associada ao oligodendrócito são considerados os principais componentes encefalitogê- A maioria (85%) dos pacientes incluídos no estudo (Tabela 1) era do sexo feminino na faixa etária de 16 a 54 anos (média 35 anos).…”