Serum cytokine profile in early and established rheumatoid arthritis

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Background: An important characteristic of immune pathology in rheumatoid arthritis (RA) is a B-cell tolerance defect, associated with autoantibodies production, and antigen-specific activation of Th-1 CD4+ T lymphocytes with an excess production of pro-inflammatory cytokines compared to anti-inflammatory ones. Pro-inflammatory cytokines contribute to the development of local inflammatory effects, induce bone destruction and pannus formation, and contribute to the development of autoimmune abnormalities and systemic manifestations. Anti-inflammatory cytokines are able to reduce the rate of joint destruction. There is evidence of the involvement of Th2 cytokines in the development of early RA. These facts suggest the need for a thorough investigation into the balance between the Th1 and Th2 types of immune response at different stages of the disease.

Aim: To assess the importance of сytokine profiling in the evaluation of immune abnormalities in RA.

Materials and methods: In this descriptive, controlled, retrospective study, we examined 118 patients with RA and 33 healthy donors as a control group. Serum IgM rheumatoid factor (RF) and C-reactive protein (CRP) levels were measured by immunonephelometry; anti-cyclic citrullinated peptide antibodies (anti-CCP) and anti-mutated citrullinated vimentin antibodies (anti-MCV) were determined by an enzyme immunoassay, cytokines levels with "xMAP" technique.

Results: Serum cytokine levels vary depending on RA duration. The cytokine profile in early RA, unlike that in established RA with a duration of more than 6 months, is characterized by higher levels of pro-inflammatory (MIP-1α), Th1 (IFN-γ), and Th17 (IL-17) cytokines, colony-stimulating factors (IL-7, G-CSF), and chemokines (IL-8, IP-10) (p < 0.05 for all parameters). In established RA, the levels of pro-inflammatory (IL-1β, -6, -15, TNF-α), anti-inflammatory (IL-1ra, IL-10, IL-13, IL-5), Th1 (IL-2, IL-12), Th2 (IL-9) cytokines and colony-stimulating factors (G-CSF, GM-CSF) correlate with the concentrations of IgM RF and antibodies to citrullinated proteins (antiCCP, anti-MCV) (all p < 0.05). There was also а correlation between CRP and pro-inflammatory (IL-1β, IL-6, TNF-α), Th1 (IL-12), Th2 (IL-5, IL-9) cytokine levels and between DAS28 and pro-inflammatory cytokine (IL-6) and colony-stimulating factor (G-CSF) levels (all p < 0.05). Conclusion: In RA, cytokines, chemokines and colony-stimulating factors mirror the inflammatory activity of the disease. Changes in blood concentrations of cytokines enable to get an insight into the complex interplay of numerous mediators of innate and acquired immunity.

About the authors

A. A. Novikov

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

Author for correspondence.
ORCID iD: 0000-0002-2738-2956

Aleksander A. Novikov – Doctor of Biol. Sci., PhD, Leading Research Fellow, Laboratory of Clinical Immunology

86 Shosse Entuziastov, Moscow, 111123

Russian Federation

Е. N. Aleksandrova

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department

ORCID iD: 0000-0003-4074-5907

Elena N. Aleksandrova – MD, PhD, Head of Laboratory of Clinical Immunology

86 Shosse Entuziastov, Moscow, 111123

G. V. Lukina

Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department;
V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences


Galina V. Lukina – MD, PhD, Professor, Head of Rheumatology Department Loginov Moscow Clinical Scientific Center, Moscow Healthcare Department; Leading Research Fellow, Safety of Anti-rheumatic Therapy Monitoring Laboratory V.A. Nasonova Research Institute of Rheumatology, Russian Academy of Medical Sciences

86 Shosse Entuziastov, Moscow, 111123, 

34A Kashirskoe shosse, Moscow, 115522


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Copyright (c) 2019 Novikov A.A., Aleksandrova Е.N., Lukina G.V.

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