Oligoclonal band

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Proteins separated by SDS-PAGE, Coomassie Brilliant Blue staining

Oligoclonal bands (OCBs) are bands of immunoglobulins that are seen when a patient's blood serum, or cerebrospinal fluid (CSF) is analyzed.

Two methods of analysis are possible: (a) protein electrophoresis, a method of analyzing the composition of fluids, also known as "agarose gel electrophoresis/Coomassie Blue staining", and (b) the combination of isoelectric focusing/silver staining. The latter is more sensitive.[1]

For the analysis of cerebrospinal fluid, a patient has a lumbar puncture performed, which collects some of his or her cerebrospinal fluid. The blood serum can be gained from a clotted blood sample. Normally it is assumed that all the proteins that appear in the CSF, but are not present in the serum, are produced intrathecally (inside the CNS). Therefore, it is normal to subtract bands in serum from bands in CSF when investigating CNS diseases.

Oligoclonal bands in multiple sclerosis[edit]

OCBs are especially important for multiple sclerosis. In MS, normally only OCBs made of immunoglobulin G antibodies are considered, though sometimes other proteins can be taken into account, like lipid-specific immunoglobulin M.[2][3] The presence of these IgM OCBs is associated with a more severe course.[4]

New techniques like "capillary isoelectric focusing immunoassay" are able to detect them in a population higher than 95%.[5]

Even more than 12 OCBs can appear in MS.[6] Each one of them represent proteins (or protein fragments) secreted by plasma cells, although why exactly these bands are present, and which proteins these bands represent, has not yet been fully elucidated. The target antigens for these antibodies is not easy to find because it requires to isolate a single kind of protein in each band, though new techniques are able to do so.[7]

In 40% of MS patients with OCBs, HHV-6 and EBV specific antibodies have been found.[8]

HHV-6 specific OCBs have also been found in other demyelinating diseases.[9][10] A lytic protein of HHV-6A virus was identified as the target of HHV-6 specific oligoclonal bands.[11]

Though early theories assumed that the OCBs were somehow pathogenic autoantigens, recent research has shown that the IgG present in the OCBs are antibodies against debris, and therefore, OCBs seem to be just a secondary effect of MS.[12] Nevertheless, OCBs remain useful as a biomarker.

Diagnostic value in MS[edit]

Oligoclonal bands are an important indicator in the diagnosis of multiple sclerosis. Up to 95% of all patients with multiple sclerosis have permanently observable oligoclonal bands.[13] At least for those with european ancestry.[14] The last available reports in 2017 were pointing to a sensitivity of 98% and specificity of 87% for differential diagnosis versus MS mimickers (specificity respect unselected population should be equal or higher)[15]

The main importance of oligoclonal bands was to demonstrate the production of intrathecal immunoglobins (IgGs) for establishing a MS diagnosis. Currently alternative methods for detection of this intrathecal synthesis have been published, and therefore it has lost some of its importance in this area. A specially interesting method is the free light chains (FLC), specially the kappa-FLCs (kFLCs). Several authors have reported that the nephelometric and ELISA FLCs determination is comparable with OCBs as markers of IgG synthesis, and kFLCs behave even better than oligoclonal bands.[16]

The remaining application for OCB's is as a tool to classify patients. It is known since long ago that OCB negative MS patients have a slower evolution. Some reports point that the underlying condition that causes the MS lesions in these patients is different. There are four pathological patterns of damage, and in the majority of patients with pattern II and III brain lesions oligoclonal bands are absent or only transiently present.[17]

Heterogeneity[edit]

It has been reported that oligoclonal bands are nearly absent in patients with pattern II and pattern III lesion types[18]

Bands in other diseases[edit]

The presence of one band (a monoclonal band) may be considered serious, such as lymphoproliferative disease, or may simply be normal—it must be interpreted in the context of each specific patient. More bands may reflect the presence of a disease. The bands tend to disappear from the cerebrospinal fluid as a person recovers from the neurological disease.

Diseases associated[edit]

Oligoclonal bands are found in:

External links[edit]

References[edit]

  1. ^ Davenport RD, Keren DF (1988). "Oligoclonal bands in cerebrospinal fluids: significance of corresponding bands in serum for diagnosis of multiple sclerosis". Clinical Chemistry. 34 (4): 764–5. PMID 3359616. 
  2. ^ Álvarez-Cermeño JC, Muñoz-Negrete FJ, Costa-Frossard L, Sainz de la Maza S, Villar LM, Rebolleda G (2016). "Intrathecal lipid-specific oligoclonal IgM synthesis associates with retinal axonal loss in multiple sclerosis". Journal of neurological sciences. 360: 41–44. doi:10.1016/j.jns.2015.11.030. 
  3. ^ Villar Luis M.; et al. "Lipid-specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab". Annals of Neurology. 77 (3): 447–457. doi:10.1002/ana.24345. PMID 25581547. 
  4. ^ Ferraro D, et al. (2015). "Cerebrospinal fluid CXCL13 in clinically isolated syndrome patients: Association with oligoclonal IgM bands and prediction of Multiple Sclerosis diagnosis". Neuroimmunology. 283: 64–69. doi:10.1016/j.jneuroim.2015.04.011. 
  5. ^ Halbgebauer S, Huss A, Buttmann M, Steinacker P, Oeckl P, Brecht I, Weishaupt A, Tumani H, Otto M (2016). "Detection of intrathecal immunoglobulin G synthesis by capillary isoelectric focusing immunoassay in oligoclonal band negative multiple sclerosis". Journal of Neurology. 263 (5): 954–960. doi:10.1007/s00415-016-8094-3. 
  6. ^ Dalla Costa Gloria; et al. (2015). "Clinical significance of the number of oligoclonal bands in patients with clinically isolated syndromes". Neuroimmunology. 289: 62–67. doi:10.1016/j.jneuroim.2015.10.009. 
  7. ^ Brändle Simone M.; Obermeier Birgit; Senel Makbule; Bruder Jessica; Mentele Reinhard; Khademi Mohsen; Olsson Tomas; Tumani Hayrettin; Kristoferitsch Wolfgang; Lottspeich Friedrich; Wekerlef Hartmut; Hohlfeld Reinhard; Dornmair Klaus. "Distinct oligoclonal band antibodies in multiple sclerosis recognize ubiquitous self-proteins". Proceedings of the National Academy of Sciences. 113: 7864–7869. doi:10.1073/pnas.1522730113. 
  8. ^ Virtanen JO, Wohler J, Fenton K, Reich DS, Jacobson S (2014). "Oligoclonal bands in multiple sclerosis reactive against two herpesviruses and association with magnetic resonance imaging findings". Multiple Sclerosis. 20 (1): 27–34. doi:10.1177/1352458513490545. PMC 5001156Freely accessible. PMID 23722324. 
  9. ^ Virtanen JO, Pietiläinen-Nicklén J, Uotila L, Färkkilä M, Vaheri A, Koskiniemi M (2011). "Intrathecal human herpesvirus 6 antibodies in multiple sclerosis and other demyelinating diseases presenting as oligoclonal bands in cerebrospinal fluid". Journal of Neuroimmunology. 237 (1–2): 93–7. doi:10.1016/j.jneuroim.2011.06.012. PMID 21767883. 
  10. ^ Pietiläinen-Nicklén J, Virtanen JO, Uotila L, Salonen O, Färkkilä M, Koskiniemi M (2014). "HHV-6-positivity in diseases with demyelination". Journal of Clinical Virology. 61 (2): 216–9. doi:10.1016/j.jcv.2014.07.006. PMID 25088617. 
  11. ^ Alenda R, Alvarez-Lafuente R, Costa-Frossard L, Arroyo R, Mirete S, Alvarez-Cermeño JC, Villar LM (2014). "Identification of the major HHV-6 antigen recognized by cerebrospinal fluid IgG in multiple sclerosis". European Journal of Neurology. 21 (8): 1096–101. doi:10.1111/ene.12435. PMID 24724742. Lay summaryHHV-6 Foundation (April 29, 2014). 
  12. ^ Wingera RC, Zamvil SS. "Antibodies in multiple sclerosis oligoclonal bands target debris". Proceedings of the National Academy of Sciences. 113: 201609246. doi:10.1073/pnas.1609246113. PMC 4948325Freely accessible. PMID 27357674. 
  13. ^ Correale J, de los Milagros M, Molinas B (2002). "Oligoclonal bands and antibody responses in Multiple Sclerosis". Journal of Neurology. 249 (4): 375–389. doi:10.1007/s004150200026. 
  14. ^ An Goris et al. Genetic variants are major determinants of CSF antibody levels in multiple sclerosis, Brain. 2015 Mar; 138(3): 632–643. 2015 Jan 23. doi: 10.1093/brain/awu405, PMCID: PMC4408440, Quote "OCBs are reported to be observed in 90–95% of patients in Northern Europe, and are composed predominantly of IgG"
  15. ^ Bernitsas E, Khan O, Razmjou S, Tselis A, Bao F, Caon C, Millis S, Seraji-Bozorgzad N1. Cerebrospinal fluid humoral immunity in the differential diagnosis of multiple sclerosis. PLoS One. 2017 Jul 20;12(7):e0181431. doi:10.1371/journal.pone.0181431. eCollection 2017. PMID 28727770
  16. ^ Fabio Duranti; Massimo Pieri; Rossella Zenobi; Diego Centonze; Fabio Buttari; Sergio Bernardini; Mariarita Dessi. "kFLC Index: a novel approach in early diagnosis of Multiple Sclerosis". International Journal of Scientific Research. 4 (8). 
  17. ^ Jarius S, König FB, Metz I, Ruprecht K, Paul F, Brück W, Wildemann B (29 Aug 2017). "Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis". J Neuroinflammation. 14: 171. doi:10.1186/s12974-017-0929-z. PMID 28851393. 
  18. ^ Jarius, S., König, F. B., Metz, I., Ruprecht, K., Paul, F., Brück, W., & Wildemann, B. (2017). Pattern II and pattern III MS are entities distinct from pattern I MS: evidence from cerebrospinal fluid analysis. Journal of Neuroinflammation, 14(1), 171.