Research Laboratory of Autoimmune and Autoinflammatory Diseases
Research Laboratory of Autoimmune and Autoinflammatory Diseases
Head of Laboratory: Mikhail Kostik, MD, DSc.
Research project: "Investigating the molecular mechanism of non-classical (non-monogenic) autoinflammatory diseases and searching for directions for their targeted therapy"
Objective
To develop approaches to clinical and laboratory diagnosis of non-classical autoinflammatory diseases, to develop and validate targeted therapy methods based on the study of the molecular mechanisms of their pathogenesis.
Tasks
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Establishing a biobank of patients with autoinflammatory diseases.
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Carrying out whole genome sequencing to identify disease-associated genetic mutations and rare variants.
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Developing approaches to the diagnosis of autoinflammatory diseases based on molecular genetic methods, data of cytokine and expression profiles and the results of molecular genetic testing.
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Establishing a laboratory of molecular immunology for working with cell cultures and experimental animals for functional tests.
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Describing new signal chains and disease development mechanisms, searching for new diseases.
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Developing approaches to targeted therapy based on the above research methods.
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Creating a clinical, laboratory, therapeutic algorithm for patients with autoinflammatory diseases.
Expected results
The project aims to generate cohorts of patients with the main forms of non-classical autoinflammatory diseases (juvenile idiopathic arthritis with systemic onset, adult Still's syndrome, idiopathic recurrent pericarditis, multifocal osteomyelitis and other undifferentiated autoinflammatory diseases), which will be examined in a prospective observation study in compliance with all the rules and principles of GCP and GMP.
Biobanking of the material will be carried out, followed by the study of expression profiles (RNA sequencing), NGS (next generation sequencing), metabolome, cytokine spectrum, minor cell populations of immunocompetent peripheral blood cells.
The prospective nature of the study and the phase course of autoinflammatory diseases will predetermine a dynamic study of the above indicators (during remission and exacerbation of the disease, initially and during therapy with genetically engineered, anticytokine drugs), making it possible to develop a multiparametric panel of highly specific diagnostic biomarkers as well as predictors for prescribing personalized, targeted biological therapy.
There are plans to conduct a registration study of domestic recombinant (IL-1) cytokine receptor antagonists for non-classical autoinflammatory diseases.
Specialists
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Mikhail Kostik, MD, DSc, Head of Laboratory, Senior Researcher
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Olga Kalinina, DSc in Biology, Leading Researcher
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Alexey Golovkin, MD, DSc, Leading Researcher
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Igor Kudryavtsev, PhD in Biology, Senior Researcher
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Ekaterina Kuchinskaya, MD, PhD, Researcher
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Valentina Myachikova, Researcher
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Ekaterina Zaikova, Junior Researcher
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Natalia Lyubimova, Junior Researcher
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Alexander Borodin, Research Assistant
- Artur Akino, Research Assistant
Major publications
- Kostik M. M., Kopchak O. L., Chikova I. A., Isupova E. A., Mushkin A. Y. Comparison of different treatment approaches of pediatric chronic non-bacterial osteomyelitis // Rheumatol Int. — 2019 Jan. — Vol. 39(1). — P. 89-96.
doi: 10.1007/s00296-018-4151-9.
- Kostik M. M., Suspitsin E. N., Guseva M. N., Levina A. S., Kazantseva A. Y., Sokolenko A. P., Imyanitov E. N. Multigene sequencing reveals heterogeneity of NLRP12-related autoinflammatory disorders // Rheumatol Int. — 2018 May — Vol.38(5). -P. 887-893.
doi: 10.1007/s00296-018-4002-8.
- Schulert G. S., Minoia F., Bohnsack J., Cron R. Q., Hashad S., Kone-Paut I., Kostik M., Lovell D., Maritsi D., Nigrovic P. A., Pal P., Ravelli A., Shimizu M., Stanevicha V., Vastert S., Woerner A., de Benedetti F., Grom A. A. Biologic therapy modifies clinical and laboratory features of macrophage activation syndrome associated with systemic juvenile idiopathic arthritis // Arthritis Care Res (Hoboken). — 2018 — Vol.70(3) — P. 409-419.
doi: 10.1002/acr.23277.
- Kostik M. M., Isupova E. A., Chikova I. A., Dubko M. F., Masalova V. V., Snegireva L. S., Kalashnikova O. V., Chasnyk V. G. Reasons for inactive disease and flare in systemic onset juvenile idiopathic arthritis patients during tocilizumab treatment // Clin Exp Rheumatol. — 2018 — Vol.36(2) — P. 335-341.
- Suspitsin E. N., Guseva M. N., Kostik M. M., Sokolenko A. P., Skripchenko N. V., Levina A. S., Goleva O. V., Dubko M. F., Tumakova A. V., Makhova M. A., Lyazina L. V., Bizin I. V., Sokolova N. E., Gabrusskaya T. V., Ditkovskaya L. V., Kozlova O. P., Vahliarskaya S. S., Kondratenko I. V., Imyanitov E. N. Next generation sequencing analysis of consecutive Russian patients with clinical suspicion of inborn errors of immunity // Clinical Genetics.- 2020 — Vol.98 — P. 231–239.
doi: 10.1111/cge.13789.
Patents
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M. M. Kostik, M. F. Dubko, V. V. Masalova, L. S. Snegireva, I. A. Chikova, E. A. Isupova. Method for diagnosing macrophage activation syndrome in patients with active systemic juvenile idiopathic arthritis (patent). Patent for invention RU 2582915 C2, 27.04.2016.
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M. M. Kostik, O. L. Kopchak, V. A. Gileva, A. Yu. Mushkin. Method for diagnosing osteomyelitis in children. Patent for invention RUS 2651091, 22.12.2016.
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A. A. Razinova, O. F. Pozdnyakova, M. M. Kostik, M. A. Silantieva, V. V. Masalova, L. S. Snegireva, A. V. Pozdnyakov. Method for diagnosing inflammatory changes in the joints in juvenile idiopathic arthritis (patent). Patent for invention RU 2682119 C1, 14.03.2019.
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M. M. Kostik, O. L. Kopchak, V. I. Zorin, A. Yu. Mushkin. Method for diagnosing osteomyelitis in children. Patent for invention RU 2707400 C1, 26.11.2019. 5. Russian-Japanese RFBR grant: 18-515-57001 Search for genes associated with the development of chronic non-bacterial osteomyelitis (NBO) in Russia and study of its molecular pathogenesis. Head: Kostik M. M.
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Golovkin S. I., Golovkin A. S., Shabaldin A. V. Method for predicting the outcomes of transient synovitis of the hip in children. Patent for invention RU 2262108 C1, 10.10.2005. Application No. 2004104524/15 dated 16.02.2004.
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Golovkin A.S., Shabaldin A.V., Lisachenko G.V. Method for diagnosing viral complications in the treatment of hemoblastosis in children. Patent for invention RU 2357256 C1, 27.05.2009. Application No. 2007141904/15 dated 12.11.2007.
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Golovkin A. S., Matveeva V. G., Grigoriev E. V., Shukevich D. L., Velikanova E. A., Barbarash L. S. Method for early diagnosis of complicated systemic inflammatory response in patients operated under cardiopulmonary bypass. Patent for invention RU 2463606 C1, 10.10.2012. Application No. 2011134573/15 dated 17.08.2011.
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Barbarash L. S., Elgudin Ya. L., Sevostyanova V. V., Golovkin A. S. Small-diameter tissue-engineered vascular graft and method for its manufacture. Patent for invention RU 2496526 C1, 27.10.2013. Application No. 2012113439/15 of 06.04.2012.
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Mukhamadiyarov R. A., Sevostyanova V. V., Golovkin A. S., Nokhrin A. V. Method for preparing biological tissue samples combined with implanted elements for examination by light microscopy. Patent for invention RU 2564895 C1, 10.10.2015. Application No. 2014123566/15 dated 09.06.2014.
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Antonova L. V., Golovkin A. S., Barbarash O. L., Barbarash L. S. Method for manufacturing a bioresorbable small-diameter hybrid vascular implant. Patent for invention RU 2504406 C1, 20.01.2014. Application No. 2012149663/15 dated 21.11.2012.
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Golovkin A. S., Ponasenko A. V., Grigoriev E. V., Shukevich D. L., Stasev A. N., Odarenko Yu. N., Barbarash L. S. Method for predicting the development of a complicated systemic inflammatory response in patients with infective endocarditis. Patent for invention RU 2520753 C1, 27.06.2014. Application No. 2013105296/15 dated 07.02.2013.
Contacts
Mikhail Kostik, Head of the Laboratory
e-mail: kostik_mm@almazovcentre.ru