Skip to main content
Log in

Differential Diagnostics of Active Progressing Multiple Sclerosis Using a Fluorescent Biomarker with Resonance Energy Transfer

  • BIOPHYSICS AND BIOCHEMISTRY
  • Published:
Bulletin of Experimental Biology and Medicine Aims and scope

Previous data showed that myelin-reactive autoantibodies found in patients with multiple sclerosis and mice with experimental autoimmune encephalomyelitis recognize and hydrolyze various fragments of myelin basic protein (MBP). Moreover, antibody-mediated cleavage of the encephalithogenic fragment MBP81-103 flanked with two fluorescent proteins can serve as a new biomarker of multiple sclerosis. Here we describe creation of the next generation of this biomarker based on antibody-dependent degradation of a new chemically synthesized fluorescent substrate with resonance energy transfer that contains fluorophore Cy5 and quencher QXL680 separated by MBP81-99 protein (Cy5-MBP81-99-QXL680). This substrate is degraded during incubation with purified antibodies and B cells from patients with multiple sclerosis, but not healthy volunteers.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Belogurov AA Jr, Kurkova IN, Friboulet A, Thomas D, Misikov VK, Zakharova MY, Suchkov SV, Kotov SV, Alehin AI, Avalle B, Souslova EA, Morse HC 3rd, Gabibov AG, Ponomarenko NA. Recognition and degradation of myelin basic protein peptides by serum autoantibodies: novel biomarker for multiple sclerosis. J. Immunol. 2008;180(2):1258-1267.

    Article  CAS  PubMed  Google Scholar 

  2. Blauth K, Owens GP, Bennett JL. The ins and outs of B cells in multiple sclerosis. Front. Immunol. 2015;6. ID 565. doi: https://doi.org/10.3389/fimmu.2015.00565.

  3. Katz Sand I, Krieger S, Farrell C, Miller AE. Diagnostic uncertainty during the transition to secondary progressive multiple sclerosis. Mult. Scler. 2014;20(12):1654-1657.

    Article  PubMed  Google Scholar 

  4. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983;33(11):1444-1452.

    Article  CAS  PubMed  Google Scholar 

  5. Lacroix-Desmazes S, Bayry J, Kaveri SV, Hayon-Sonsino D, Thorenoor N, Charpentier J, Luyt CE, Mira JP, Nagaraja V, Kazatchkine MD, Dhainaut JF, Mallet VO. High levels of catalytic antibodies correlate with favorable outcome in sepsis. Proc. Natl Acad. Sci. USA. 2005;102(11):4109-4113.

    Article  CAS  PubMed  Google Scholar 

  6. Lublin FD, Reingold SC, Cohen JA, Cutter GR, Sørensen PS, Thompson AJ, Wolinsky JS, Balcer LJ, Banwell B, Barkhof F, Bebo B Jr, Calabresi PA, Clanet M, Comi G, Fox RJ, Freedman MS, Goodman AD, Inglese M, Kappos L, Kieseier BC, Lincoln JA, Lubetzki C, Miller AE, Montalban X, O’Connor PW, Petkau J, Pozzilli C, Rudick RA, Sormani MP, Stüve O, Waubant E, Polman CH. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278-286.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Mizoguchi A, Mizoguchi E, Takedatsu H, Blumberg RS, Bhan AK. Chronic intestinal inflammatory condition generates IL-10-producing regulatory B cell subset characterized by CD1d upregulation. Immunity. 2002;16(2):219-230.

    Article  CAS  PubMed  Google Scholar 

  8. Ponomarenko NA, Durova OM, Vorobiev II, Aleksandrova ES, Telegin GB, Chamborant OG, Sidorik LL, Suchkov SV, Alekberova ZS, Gnuchev NV, Gabibov AG. Catalytic antibodies in clinical and experimental pathology: human and mouse models. J. Immunol. Methods. 2002;269(1-2):197-211.

    Article  CAS  PubMed  Google Scholar 

  9. Ponomarenko NA, Durova OM, Vorobiev II, Belogurov AA Jr, Kurkova IN, Petrenko AG, Telegin GB, Suchkov SV, Kiselev SL, Lagarkova MA, Govorun VM, Serebryakova MV, Avalle B, Tornatore P, Karavanov A, Morse HC 3rd, Thomas D, Friboulet A, Gabibov AG. Autoantibodies to myelin basic protein catalyze site-specific degradation of their antigen. Proc. Natl Acad. Sci. USA. 2006;103(2):281-286.

  10. Ponomarenko NA, Durova OM, Vorobiev II, Belogurov AA, Telegin GB, Suchkov SV, Misikov VK, Morse HC 3rd, Gabibov AG. Catalytic activity of autoantibodies toward myelin basic protein correlates with the scores on the multiple sclerosis expanded disability status scale. Immunol. Lett. 2006;103(1):45-50.

  11. Pulendran B, Ahmed R. Immunological mechanisms of vaccination. Nat. Immunol. 2011;12(6):509-517.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shuster AM, Gololobov GV, Kvashuk OA, Bogomolova AE, Smirnov IV, Gabibov AG. DNA hydrolyzing autoantibodies. Science. 1992;256:665-667.

    Article  CAS  PubMed  Google Scholar 

  13. von Büdingen HC, Palanichamy A, Lehmann-Horn K, Michel BA, Zamvil SS. Update on the autoimmune pathology of multiple sclerosis: B cells as disease-drivers and therapeutic targets. Eur. Neurol. 2015;73(3-4):238-246.

    Article  CAS  Google Scholar 

  14. Yang YH, Chang CJ, Chuang YH, Hsu HY, Chen PP, Chiang BL. Identification of anti-prothrombin antibodies in the antiphospholipid syndrome that display the prothrombinase activity. Rheumatology (Oxford). 2010;49(1):34-42.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A. A. Belogurov Jr.

Additional information

Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 167, No. 3, pp. 299-305, March, 2019

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lomakin, Y.A., Kudryaeva, A.A., Kostin, N.N. et al. Differential Diagnostics of Active Progressing Multiple Sclerosis Using a Fluorescent Biomarker with Resonance Energy Transfer. Bull Exp Biol Med 167, 329–334 (2019). https://doi.org/10.1007/s10517-019-04520-1

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10517-019-04520-1

Key Words

Navigation