Polyreactive monoclonal autoantibodies in multiple sclerosis: functional selection from phage display library and characterization by deep sequencing analysis.
Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system that primarily affects young and middle-aged people. It is widely accepted that B lymphocyte activation is required for MS progression. Despite the fact that the exact triggering mechanisms of MS remain enigmatic, one may suggest that MS can be induced by viral or bacterial infection in combination with specific genetic and environmental factors. Using deep sequencing and functional selection methodologies we characterized clones of poly- and cross-reactive antibodies that are capable of simultaneous recognition of viral proteins and autoantigens. The latter, in turn, possibly may trigger MS progression through molecular mimicry. It was identified that two cross-reactive antigens are probably recognized by light or heavy chains individually. According to the high structural homology between selected autoantibodies and a number of various antiviral IgGs, we suggest that a wide range of pathogens, instead of a single virus, be regarded as possible triggers of MS.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.
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Lomakin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.
M Yu
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Zakharova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia ; Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia.
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Belogurov
Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences, 127994, Moscow, Russia ; Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991, Moscow, Russia.
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Bykova
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.
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Dronina
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia ; Genomics Core Facility, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia.
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Tupikin
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.
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Knorre
Moscow Multiple Sclerosis Center at the City Hospital #11, 127018, Moscow, Russia ; Pirogov Russian National Research Medical University, Department of Fundamental and Clinical Neurology and Neurosurgery, 117997, Moscow, Russia.
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Boyko
Vavilov Institute of General Genetics, Russian Academy of Sciences, 119991, Moscow, Russia ; Department of Oncology, Division of Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, 21218, Baltimore, Maryland, USA ; State Research Institute of Genetics and Selection of Industrial Microorganisms GosNIIGenetika, 117545, Moscow, Russia.
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Favorov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia ; Genomics Core Facility, Siberian Branch, Russian Academy of Sciences, 630090, Novosibirsk, Russia.
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Kabilov
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia.
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Ponomarenko
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, 117997, Moscow, Russia ; Institute of Gene Biology, Russian Academy of Sciences, 119334, Moscow, Russia ; Faculty of Chemistry, Lomonosov Moscow State University, 119991, Moscow, Russia.
Gabibov
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Gabibov
Multiple sclerosis; autoreactive B cells; cross-reactivity; deep sequencing; myelin basic protein; viral triggers