Original article| Volume 45, 102412, October 2020

CSF oligoclonal band frequency in a Cuban cohort of patients with multiple sclerosis. comparison with Latin American countries and association with latitude


      • The prevalence of OCBs in a cohort of Cuban MS patients was 87%.
      • OCB frequency in Cuban MS patients was slightly lower, but close to Caucasians.
      • A relationship between OCB prevalence and latitude might be present in Latin America.


      Background. The diagnostic sensitivity of CSF specific oligoclonal bands (OCBs) in multiple sclerosis (MS), using state of the art methods, has been clearly established to be over 95% in patients with a predominantly Caucasian background. This is not the case for other geographical regions, where reports of OCB prevalence can be much lower, and a relationship between OCB frequency and latitude has been suggested. Objective. The aim of the present study was to assess the frequency of OCBs in a cohort of MS patients evaluated at the Institute of Neurology and Neurosurgery (Havana, Cuba), and to review the scientific literature in order to investigate the possible relationship between OCB status and latitude in the region of Latin America. Methods. Fifty-three patients (47 with definite MS and 6 with clinically isolated syndrome – CIS) were included. Isoelectric focusing (IEF) with IgG immunoblotting for OCB analyses, was performed placing paired CSF and serum samples in the same analytical run. PubMed, Scielo and Google Scholar were searched for papers containing information concerning CSF OCB status (employing isoelectric focusing with IgG immunoblotting) in patients with definite MS in Latin America and the Caribbean. Results. In Cuban patients with definite MS, an OCB prevalence of 87% was observed, while the frequency in CIS patients was lower (67%). The prevailing pattern was that of OCBs restricted to the CSF (type 2), which was observed in 71% of definite MS patients and in all CIS patients with intrathecal IgG synthesis. OCB prevalence was slightly lower, but very close to that reported in Caucasian populations. Comparison with other Latin American countries revealed a significant correlation between OCB prevalence and latitude. Conclusions. A prevalence of CSF restricted OCBs of 87% was observed in definite MS patients, a frequency which was slightly lower, but similar to that reported in Caucasian populations. The analysis of OCB frequency in Latin American countries revealed a possible relationship between OCB prevalence and latitude, but this must be further investigated in more countries and larger samples of patients.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Multiple Sclerosis and Related Disorders
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Arrambide G.
        • Tintore M.
        • Espejo C.
        • et al.
        The value of oligoclonal bands in the multiple sclerosis diagnostic criteria.
        Brain. 2018; 141: 1075-1084
        • Deisenhammer F.
        • Zetterberg H.
        • Fitzner B.
        • et al.
        The cerebrospinal fluid in multiple sclerosis.
        Front. Immunol. 2019; 10: 726
        • Thompson A.J.
        • Baranzini S.E.
        • Geurts J.
        • et al.
        Multiple sclerosis.
        Lancet North Am. Ed. 2018; 391: 1622-1636
        • Thompson A.J.
        • Banwell B.L.
        • Barkhof F.
        • et al.
        Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria.
        Lancet Neurol. 2018; 17: 162-173
        • Dobson R.
        • Ramagopalan S.
        • Davis A.
        • et al.
        Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude.
        J. Neurol. Neurosurg. Psychiat. 2013; 84: 909-914
        • Zeman D.
        • Hradilek P.
        • Kusnierova P.
        • et al.
        Oligoclonal free light chains in cerebrospinal fluid as markers of intrathecal inflammation. Comparison with oligoclonal igG.
        Biomed. Pap. 2015; 159: 104-113
        • Siritho S.
        • Freedman M.S.
        The prognostic significance of cerebrospinal fluid in multiple sclerosis.
        J. Neurol. Sci. 2009; 279: 21-25
        • Simonsen C.S.
        • HØ Flemmen
        • Lauritzen T.
        • et al.
        The diagnostic value of IgG index versus oligoclonal bands in cerebrospinal fluid of patients with multiple sclerosis.
        Mult. Scler. J. Exp. Transl. Clin. 2020; 6205521731990129
        • Schwenkenbecher P.
        • Konen F.F.
        • Wurster U.
        • et al.
        The persisting significance of oligoclonal bands in the dawning era of kappa free light chains for the diagnosis of multiple sclerosis.
        Int. J. Mol. Sci. 2018; 19: 3796
        • Villar L.M.
        • Masterman T.
        • Casanova B.
        • et al.
        CSF oligoclonal band patterns reveal disease heterogeneity in multiple sclerosis.
        J. Neuroimmunol. 2009; 211: 101-104
        • Franciotta D.
        • Columba-Cabezas S.
        • Andreoni L.
        • et al.
        Oligoclonal IgG band patterns in inflammatory demyelinating human and mouse diseases.
        J. Neuroimmunol. 2008; 200: 125-128
        • Cobo-Calvo Á.
        • d’Indy H.
        • Ruiz A.
        • et al.
        Frequency of myelin oligodendrocyte glycoprotein antibody in multiple sclerosis: a multicenter cross-sectional study.
        Neurol. Neuroimmunol. Neuroinflam. 2019; 7: e649
        • Mero I.-.L.
        • Gustavsen M.W.
        • Sæther H.S.
        • et al.
        Oligoclonal band status in Scandinavian multiple sclerosis patients is associated with specific genetic risk alleles.
        PLoS ONE. 2013; 8: e58352
        • Siritho S.
        • Prayoonwiwat N.
        A retrospective study of multiple sclerosis in Siriraj Hospital, Bankok, Thailand.
        Can. J. Neurol. Sci. 2007; 34: 99-104
        • Lu T.
        • Zhao L.
        • Sun X.
        • et al.
        Comparison of multiple sclerosis patients with and without oligoclonal IgG bands in South China.
        J. Clin. Neurosci. 2019; 66: 51-55
        • Yoshimura S.
        • Isobe N.
        • Matsushita T.
        • et al.
        Genetic and infectious profiles influence cerebrospinal fluid IgG abnormality in Japanese multiple sclerosis patients.
        PLoS ONE. 2014; 9: e95367
        • Niino M.
        • Sato S.
        • Fukazawa T.
        • et al.
        Latitude and HLA-DRB1 alleles independently affect the emergence of cerebrospinal fluid IgG abnormality in multiple sclerosis.
        Mult. Scler. 2015; 21: 1112-1120
        • Lechner-Scott J.
        • Spencer B.
        • de Malmanche T.
        • et al.
        The frequency of CSF oligoclonal banding in multiple sclerosis increases with latitude.
        Mult. Scler. 2012; 18: 974-982
        • Petzold A.
        Intrathecal oligoclonal IgG synthesis in multiple sclerosis.
        J. Neuroimmunol. 2013; 262: 1-10
        • da Gama P.D.
        • dos Ramos Machado L.
        • Livramento J.A.
        • et al.
        Oligoclonal bands in cerebrospinal fluid of black patients with multiple sclerosis.
        Biomed. Res. Int. 2015; 2015217961
        • Correa-Díaz E.P.
        • Ortiz M.A.
        • Toral A.M.
        • et al.
        Prevalence of multiple sclerosis in Cuenca, Ecuador.
        Mult. Scler. J. Exp. Transl. Clin. 2019; 52055217319884952
        • Cabrera-Limpias S.
        • González J.C.
        • Romero-Sánchez C.
        • et al.
        Bandas oligoclonales en lıquido cefalorraquıdeo de pacientes con esclerosis múltiple del Hospital Militar Central, Bogota DC.
        Acta Neurol. Colomb. 2012; 28: 80-84
        • Rojas J.I.
        • Tizio S.
        • Patrucco L.
        • Cristiano E
        Oligoclonal bands in multiple sclerosis patients: worse prognosis?.
        Neurol. Res. 2012; 34: 889-892
        • Sáez M.S.
        • Rojas J.I.
        • Lorenzón M.V.
        • et al.
        Validation of CSF free light chain in diagnosis and prognosis of multiple sclerosis and clinically isolated syndrome: prospective cohort study in Buenos Aires.
        J. Neurol. 2019; 266: 112-118
        • Ruocco H.H.
        • Brando C.O.
        • Farias A.S.
        • et al.
        Quantitative MRI and cerebrospinal fluid inflammatory mediators in brazilian patients with relapsing-remitting multiple sclerosis before and after treatment with immunomodulators: a longitudinal study.
        Neuroimmunomod. 2012; 19: 277-282
        • Robinson-Agramonte M.
        • Reiber H.
        • Cabrera-Gomez J.A.
        • et al.
        Intrathecal polyspecific immune response to neurotropic viruses in multiple sclerosis: a comparative report from Cuban patients.
        Acta Neurol. Scand. 2007; 115: 312-318
        • Oehninger-Gatti C.
        • Buzó R A.J
        Utilidad de los marcadores biológicos en el diagnóstico y seguimiento de los pacientes con esclerosis múltiple. Test de los cinco humores.
        Rev. Neurol. 2000; 30: 977-979
        • Leone M.A.
        • Barizzone N.
        • Esposito F.
        • et al.
        Association of genetic markers with csf oligoclonal bands in multiple sclerosis patients.
        PLoS ONE. 2013; 8: e64408
        • Lublin F.D.
        • Reingold S.C.
        • Cohen J.A.
        • et al.
        Defining the clinical course of multiple sclerosis: the 2013 revisions.
        Neurology. 2014; 83: 278-286
        • Kurtzke J.F.
        Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).
        Neurology. 1983; 33: 1444-1452
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • Randall R.J
        Protein measurement with the Folin phenol reagent.
        J. Biol. Chem. 1951; 193: 265-275
        • Gaitán M.I.
        • Correale J
        Multiple sclerosis misdiagnosis: a persistent problem to solve.
        Front. Neurol. 2019; 10: 466
        • González-Quevedo A.
        • Peña Sánchez M.
        • González-García S
        Cerebrospinal fluid total protein reference intervals derived from 20 years of patient data.
        J. Lab. Precis. Med. 2018; 3: 35
        • Freedman M.S.
        • Thompson E.J.
        • Deisenhammer F.
        • et al.
        Recommended standard of cerebrospinal fluid analysis in the diagnosis of multiple sclerosis: a consensus statement.
        Arch. Neurol. 2005; 62: 865-870
        • Informe nacional del Censo de población y vivienda
        Oficina nacional de estadística e información. República de Cuba.
        Enero. 2012; : 2014
        • Jarius S.
        • König F.B.
        • Metz I.
        • et al.
        Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis.
        J. Neuroinflam. 2017; 14: 171
        • Tintoré M.
        • Rovira A.
        • Río J.
        • et al.
        Do oligoclonal bands add information to MRI in first attacks of multiple sclerosis?.
        Neurology. 2008; 70: 1079-1083
        • Robinson-Agramonte M.A
        Asimilación del método de focalización isoeléctrica en agarosa y aplicación del ELISA al estudio de la respuesta de anticuerpos en SNC de personas con esclerosis múltiple.
        Universidad de Ciencias Médicas de La Habana, 2010 (PhD thesisAvailable from)
        • Cabrera-Gómez J.A.
        • Santana-Capote E.
        • Echazábal-Santana N.
        • et al.
        [Actual status of multiple sclerosis in Cuba. National cooperative group for the clinical trial “Recombinant interferon alpha-2b in multiple sclerosis”].
        Rev. Neurol. 2000; 31: 482-493
        • Cabrera-Gómez J.A
        Estado actual de la esclerosis múltiple en el Caribe..
        Arriagada C, Nogales-Gaete (Eds) Esclerosis Múltiple. Una mirada Ibero-Panamericana. Arrynog - Ediciones, Santiago de Chile2002: 155-182
        • Koch-Henriksen N.
        • Sorensen P.S.
        The changing demographic pattern of multiple clerosis epidemiology.
        Lancet Neurol. 2010; 9: 520-532
        • Rivera V.M.
        • Medina M.T.
        • Duron R.M.
        • et al.
        Multiple sclerosis care in Latin America.
        Neurology. 2014; 82: 1660-1661
        • Marcheco-Teruel B.
        • Parra E.J.
        • Fuentes-Smith E.
        • et al.
        Cuba: exploring the history of admixture and the genetic basis of pigmentation using autosomal and uniparental markers.
        PLos Genet. 2014; 10e1004488
        • Carrá A.
        • MÁ Macías-Islas
        • Gabbai A.A.
        • et al.
        Optimizing outcomes in multiple sclerosis: consensus guidelines for the diagnosis and treatment of multiple sclerosis in Latin America.
        Ther. Adv. Neurol. Disord. 2011; 4: 349-360
        • Rivera V.M.
        Multiple sclerosis: a global concern with multiple challenges in an Era of advanced therapeutic complex molecules and biological medicines.
        Biomed. MDPI. 2018; 6: 112