Determinação de Anticorpos Anti-Mielina na Esclerose Múltipla

 

Eduardo Lima*, Joana Guimarães††, Ana Pereira*, Abília Bodas*, Luís Delgado*‡, Maria José Sá*

*Laboratório de Imunologia, Hospital de São João, Porto; † †Serviço de Neurologia, Hospital de São João, Porto; ‡ Serviço de Imunologia, Faculdade de Medicina, Universidade do Porto

 

Introdução: A Esclerose Múltipla é uma doença desmielinizante primária de carácter autoimune, envolvendo diferentes mecanismos imunopatológicos. Pensa-se que anticorpos dirigidos contra antigénios da mielina podem estar associados aos danos na mielina ou surgirem devido a estes, pelo que, o seu doseamento poderá constituir um marcador de evolução da doença. No entanto, a positividade desta pesquisa pode levantar dúvidas em termos de valorização clínica dada a descrição destes auto-anticorpos também em indivíduos sem doença. O objectivo deste trabalho foi a avaliação da presença de auto-anticorpos para a mielina em pacientes com o diagnóstico de Esclerose Múltipla, comparativamente a amostras de controlo, avaliando a sua associação com sintomas clínicos em pacientes com diferentes formas clínicas da Esclerose Múltipla. Métodos: A pesquisa de anticorpos para a mielina foi realizada por uma técnica de imunofluorescência indirecta usando como substrato, nervo periférico de primata (EUROIMMUN®). Foram estudados 34 doentes (14M/11H), observados no serviço de Neurologia do Hospital de São João: 8 com forma monosintomática em surto, 11 com forma Surto/Remissão (SR) em remissão, 11 com forma SR em surto e 4 com forma Primária Progressiva (PP) em remissão. A população de controlo foi constituída por 25 amostras de indivíduos saudáveis (26M/8H). Resultados: Encontraram-se diferenças significativas nas duas populações em relação à presença de anticorpos para a mielina (p<0,001). A análise dos diferentes tipos clínicos demonstrou uma prevalência de 87,5% nos casos com SCI, 77,3% na forma SR e 75,0% na forma PP. Em relação à situação clínica, 94,7% dos doentes em surto possuíam anticorpos anti-mielina enquanto que nos doentes em remissão 60,0% foram positivos. No grupo sem patologia, 32,0% apresentou positividade para os anticorpos anti-mielina. Conclusões: Apesar deste teste não ser específico na Esclerose Múltipla, na população de doentes estudada verificou-se uma maior prevalência dos anticorpos anti-mielina por imunofluorescência indirecta nos pacientes em surto. Até que novos e melhores marcadores serológicos estejam disponíveis, este teste poderá ser útil para monitorizar pacientes com diagnóstico definitivo ou possível de Esclerose Múltipla, na qual a presença destes auto anticorpos poderá indicar um possível surto.

Palavras-chave: esclerose múltipla; auto-anticorpos; mielina; imunofluorescência indirecta.

 

Anti-Myelin Autoantibodies in Multiple Sclerosis

Introduction: Multiple Sclerosis (MS) is a primary demyelinating disease of autoimmune ethiology with different immunopathologic mechanisms. Anti-myelin autoantibodies may be associated with myelin damage and a possible marker of the disease evolution. However, the clinical usefulness of these autoantibodies is questionable as they may be present in healthy individuals. The aim of this work was the evaluation of autoantibodies against myelin in patients with MS comparatively with control samples, and their association with differents clinical types. Methology: For the search of anti-myelin antibodies we used indirect immunofluorescence in primate peripheral nerves (EUROIMMUN®). Thirty four patients (14 female/11 male) followed in the Neurology department were studied: 8 with the Clinically Isolated Syndrome (CIS) with relapse, 11 with Relapsing/Remitting (RR) in remission, 11 with RR with relapse and 4 with Primary Progressive (PP); 25 samples of healthy individuals (26 female/8 male) were studied as controls. Results: The presence of autoantibodies to myelin was signifiantly different in the two studied populations (p<0.001). Within the different clinical types we found a prevalence of 87.5% in CIS, 77.3% in RR and 75.0% in the patients with PP. Most patients (94.7%) in relapse had antibodies against myelin versus 60.0% of those in remision. In the control group, 32.0% presented anti-myelin antibodies. Conclusions: Although this test was not specific for MS, in the patient population studied the presence of anti-myelin antibodies by indirect immunofluorescence was higher in those in relapse. Until new and better serologic markers are available, this test may be useful to monitor patients with possible or definitive diagnosis of MS, in witch the presence of anti-myelin antibodies may support a possible relapse.

Key-words: multiple sclerosis; auto-antibody; myelin; indirect immunofluorescence.

 

 

Texto completo disponível apenas em PDF.

Full text only available in PDF format.

 

 

REFERÊNCIAS

1 -Thrower BW. Clinically isolated syndromes: predicting and delaying multiple sclerosis. Neurology 2007;68:S12-5.

        [ Links ]

2 - Brettschneider J, Petzold A, Junker A, Tumani H. Axonal damage markers in the cerebrospinal fluid of patients with clinically isolated syndrome improve predicting conversion to definite multiple sclerosis. Mult Scler 2006;2:143-8.

3 -Motamed MR, Najimi N, Fereshtehnejad SM. The effect of interferon-beta1a on relapses and progression of disability in patients with clinically isolated syndromes (CIS) suggestive of multiple sclerosis. Clin Neurol Neurosurg 2007;109:344-9.

4 -Miller JR. The importance of early diagnosis of multiple sclerosis. J Manag Care Pharm 2004;10:S4-11.

5 -Koch M, Heersema D, Mostert J, Teelken A, De Keyser J. Cerebrospinal fluid oligoclonal bands and progression of disability in multiple sclerosis. Eur J Neurol 2007;14: 797-800.

6 -Doggrell SA. Is natalizumab a breakthrough in the treatment of multiple sclerosis? Expert Opin Pharmacother 2003;4:999-1001.

7 -Kieseier BC, Wiendl H, Hemmer B, Hartung HP. Treatment and treatment trials in multiple sclerosis. Curr Opin Neurol 2007;20:286-93.

8 -Lassmann H, Brück W, Lucchinetti C. Heterogeneity of multiple sclerosis pathogenesis: implications for diagnosis and therapy. Trends Mol Med 2001;7:115-21.

9 -McDonald WI, Compston A, Edan G. Recommended Diagnostic Criteria for Multiple Sclerosis: Guideline from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurology 2001;50:121-7.

10 -Frohman EM, Racke MK, Raine. Multiple Sclerosis- The Plaque and Its pathogenesis. N Engl J Med 2006;354: 942-55.

11 -Berger T, Rubner P, Scautzer F et al. Antimyelin Antibodies as a Predictor of Clinically Definite Multiple Sclerosis after a First Demyelinating Event. N Engl J Med 2003;349:139-45.

12 -Kerlero R, Honegger P, Lassmann H, Matthieu J. Demyelination induced in aggregating brain cell cultures by a monoclonal antibody against myelin/oligodendrocyte glycoprotein. J Neurochem 1990;55:583-7.

13 -Angelucci F, Mirabella M, Frisullo G. Serum levels of anti-myelin antibodies in relapsing-remitting multiple sclerosis patients during different phases of disease activity and immunomodulatory therapy. Dis Markers 2005;21:49-55.

14 -Lolli F, Mazzanti B, Pazzagli M. The glycopeptide CSF114(Glc) detects serum antibodiesin multiple sclerosis. J Neuroimmunol 2005;167:131-7.

15 -Gaertner S, Graaf KL, Greve B, Weissert R. Antibodies against glycosylated native MOG are elevated in patients with multiple sclerosis. Neurology 2004;63:2238-383.

16 -Lalive PH, Menge T, Delarasse C, Gaspera BD, Pham-Dinh D, Villoslada P. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis. Proc Natl Acad Sci USA 2006;103: 2280-5.

17 -Khalil M, Reindl M, Luterotti A, Kuenz B, Ehling R, Gneiss C et al, Epitope specificity of serum antibodies against the extracelular domain of myelin oligodendrocyte glycoprotein: Influence of relapses and immunomodulatory treatments. J Neuroimmunol 2006;174:147-56.

18 -Breij ECW, Heijen P, van der Goes A, Teunissen CE, Polman CH, Dijkstra . Myelin flow citometry assay detects enhanced levels of antibodies to human whole myelin in a subpopulation of multiple sclerosis patients. J Neuroimmunol 2006;176:106-14.

19 -Mantegazza R, Cristaldini P, Bernasconi, P. Anti-MOG autoantibodies in Italian multiple sclerosis patients: specificity, sensitivity and clinical association. Int Immunol 2004;16: 559-65.

20 -Lim ET, Berger T, Reidl M. Anti-myelin antibodies do not allow earlier diagnosis of multiple sclerosis. Mul Scler 2005;11:492-4.

21 -Zadro I, Brinar V, Horvat G, Brinar M. Clinical Relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis. Clin Neurol Neurosurg 2007;109:23-6.

22 -Zadro I, Brinar V, Horvat G, Brinar M. Clinical Relevance of antibodies against myelin oligodendrocyte glycoprotein in different clinical types of multiple sclerosis. Clin Neurol Neurosurg 2007;109:23-6.

23 -Lampsona V, Franciotta D, Furlan R . Similar low frequency of anti-MOG IgG and IgM in MS patients and healthy subjects. Neurology 2004;62:2092-4.

24 -Marta CM, Oliver AR, Sweet RA. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosilated epitopes and perturb oligodendrocyte physiology. Proc Natl Acad Sci USA 2005;102:13992-7.

25 -Reindl M, Khalil M, Berger T. Antibodies as biological markers for pathophysiological processes in MS. J Neuroimmunol 2006;180:50-62.

26 -Robinson W H, Fontoura P, Lee B J et al. Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nat Biotechnol 2003;21:1033-9.

 

Correspondência:

Dr. Eduardo Lima

Laboratório de Imunologia

Hospital de São João

Alameda Prof. Hernâni Monteiro

4200-319 Porto

e-mail: edlima1982@hotmail.com