Diagnostic significance of intrathecally synthesized immunoglobulins against neurotropic viruses (MRZ-reaction) in diagnosis of multiple sclerosis

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Abstract

Multiple sclerosis is chronic demyelinating disease of the central nervous system with autoimmune inflammation and accretive neurodegeneration. One of the characteristics of autoimmune inflammation in multiple sclerosis is a polyspecific intrathecal humoral immune response against neurotropic viruses (Measles, Rubella and varicella Zoster) called MRZ-reaction. This immune response is based on polyclonal activation of mature B lymphocytes in the central nervous system and intrathecal synthesis of antibodies to anamnestic antigens unrelated to viral replication in the central nervous system as well as serum antibody release. Immunoglobulins produced against neurotropic viruses are an integral part of the oligoclonal antibody pool in the cerebrospinal fluid. Because immunoglobulins can penetrate the blood brain barrier, not only serum and cerebrospinal fluid specific antibody indices are calculated, but also blood-brain barrier antibody permeability (Qalbumin, QIgG) are taken into account to assess their intrathecal synthesis. The aim of the study was to assess the informative value of the intrathecal antibodies against neurotropic viruses (MRZ-reaction) in multiple sclerosis. There were enrolled 60 patients divided into 2 groups: group 1 — 35 patients diagnosed with multiple sclerosis, group 2 — 25 patients with inflammatory and non-inflammatory disоrders of the central nervous system. Paired cerebrospinal fluid and serum samples were collected from all patients to measure level of oligoclonal IgG, immunoglobulin free kappa and lambda light chains, IgG index and specific antibodies indices, followed by assessing magnitude of MRZ-reaction. We found that the MRZ-reaction was the most specific test to diagnose multiple sclerosis. Intrathecally produced antibodies against neurotropic viruses were detected in 3 of 35 multiple sclerosis patients with lacking oligoclonal IgG antibodies. In addition, a relationship between MRZ-reaction and degree of EDSS disability was found in MS patients: peak EDSS score was reported in patients with intrathecally synthesized antibodies against 3 viral agents, whereas the minimum EDSS score — among MRZ-negative patients. Thus, assessing MRZ-reaction seems rational for confirming MS diagnosis in case of other negative laboratory tests (oligoclonal immunoglobulins and free kappa/lambda light chains in cerebrospinal fluid) allowing to improves diagnostic accuracy and evaluation of MS severity.

About the authors

A. N. Moshnikova

Pavlov First St. Petersburg State Medical University

Author for correspondence.
Email: moshnikova-anna@mail.ru

Anna N. Moshnikova, Junior Researcher, Autoimmune Diseases Diagnostics Laboratory, Scientific and Methodological Center for Molecular Medicine

197022, St. Petersburg, L. Tolstoy str., 6/8.

Phone: +7 (812) 499-71-94 (office).

Russian Federation

V. K. Maksimchuk

Pavlov First St. Petersburg State Medical University

Email: guravkon@mail.ru

6th Year Student

St. Petersburg

Russian Federation

S. V. Lapin

Pavlov First St. Petersburg State Medical University

Email: svlapin@mail.ru

PhD (Medicine), Head of the Autoimmune Diseases Diagnostics Laboratory, Scientific and Methodological Center for Molecular Medicine

St. Petersburg

Russian Federation

V. D. Nazarov

Pavlov First St. Petersburg State Medical University

Email: nazarov19932@mail.ru

Junior Researcher, Autoimmune Diseases Diagnostics Laboratory, Scientific and Methodological Center for Molecular Medicine

St. Petersburg

Russian Federation

E. A. Surkova

Pavlov First St. Petersburg State Medical University

Email: easurkova@mail.ru

PhD (Biology), Senior Researcher, Autoimmune Diseases Diagnostics Laboratory, Scientific and Methodological Center for Molecular Medicine

St. Petersburg

Russian Federation

S. A. Novikov

Pavlov First St. Petersburg State Medical University

Email: fake@neicon.ru

PhD, MD (Medicine), Professor of the Department of Ophthalmology

St. Petersburg

Russian Federation

G. S. Makshakov

City Center for Multiple Sclerosis and Autoimmune Diseases Treatment, St. Petersburg

Email: g.makshakov@centrems.com
ORCID iD: 0000-0001-6831-0441

Neurologist, City Center for Multiple Sclerosis and Autoimmune Diseases Treatment

St. Petersburg

Russian Federation

I. Yu. Krutetskaya

A.M. Granov Russian Research Center for Radiology and Surgical Technologies

Email: mpsamoylovich@gmail.com

PhD (Biology), Senior Researcher, Laboratory of Hybridoma Technology

St. Petersburg

Russian Federation

V. S. Krasnov

Pavlov First St. Petersburg State Medical University

Email: krasnov_volod@mail.ru

Associate Professor, Department of Neurology

St. Petersburg

Russian Federation

Ya. B. Kushnir

Pavlov First St. Petersburg State Medical University

Email: kushnir.yana2014@yandex.ru

Neurologist, Neurology Clinic No. 1

St. Petersburg

Russian Federation

N. A. Neofidov

Pavlov First St. Petersburg State Medical University; City Center for Multiple Sclerosis and Autoimmune Diseases Treatment, St. Petersburg

Email: n.neofidov@centrems.com
ORCID iD: 0000-0001-9043-9823

PhD Student, Department of Neurology; Neurologist

St. Petersburg

Russian Federation

N. A. Totolian

Pavlov First St. Petersburg State Medical University

Email: ntotolyan@mail.ru

PhD, MD (Medicine), Professor of the Department of Neurology

St. Petersburg

Russian Federation

A. A. Skoromets

Pavlov First St. Petersburg State Medical University

Email: askoromets@gmail.com

RAS Full Member, PhD, MD (Medicine), Professor, Head of the Department of Neurology

St. Petersburg

Russian Federation

E. P. Evdoshenko

Pavlov First St. Petersburg State Medical University; City Center for Multiple Sclerosis and Autoimmune Diseases Treatment, St. Petersburg

Email: e.evdoshenko@centrems.com
ORCID iD: 0000-0002-8006-237X

PhD (Medicine), Neurologist, Head of the City Center for Multiple Sclerosis and Autoimmune Diseases Treatment; Doctoral Student, Department of Neurology

St. Petersburg

Russian Federation

Areg A. Totolian

Pavlov First St. Petersburg State Medical University; St. Petersburg Pasteur Institute

Email: totolian@spbraaci.ru

RAS Full Member, PhD, MD (Medicine), Professor, Head of the Department of Immunology; Director, St. Petersburg Pasteur Institute

St. Petersburg

Russian Federation

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Copyright (c) 2019 Moshnikova A.N., Maksimchuk V.K., Lapin S.V., Nazarov V.D., Surkova E.A., Novikov S.A., Makshakov G.S., Krutetskaya I.Y., Krasnov V.S., Kushnir Y.B., Neofidov N.A., Totolian N.A., Skoromets A.A., Evdoshenko E.P., Totolian A.A.

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