Associations between Viral Infection History Symptoms, Granulocyte Reactive Oxygen Species Activity, and Active Rheumatoid Arthritis Disease in Untreated Women at Onset: Results from a Longitudinal Cohort Study of Tatarstan Women.

Marina I Arleevskaya,Yves Renaudineau,Albina Z Shafigullina,Yulia V Filina,Julie Lemerle

doi:10.3389/fimmu.2017.01725

Abstract

To evaluate the effects of infectious episodes at early stages of rheumatoid arthritis (eRA) development, 59 untreated eRA patients, 77 first-degree relatives, from a longitudinal Tatarstan women cohort, were included, and compared to 67 healthy women without rheumatoid arthritis (RA) in their family history. At inclusion, informations were collected regarding both the type and incidence of infectious symptom episodes in the preceding year, and granulocyte reactive oxygen species (ROS) were studied at the basal level and after stimulation with serum-treated zymosan (STZ). In the eRA group, clinical [disease activity score (DAS28), health assessment questionnaire] and biological parameters associated with inflammation (erythrocyte sedimentation rate, C-reactive protein) or with RA [rheumatoid factor, anticyclic citrullinated peptide (anti-CCP2) antibodies] were evaluated. An elevated incidence of infection events in the previous year characterized the eRA and relative groups. In addition, a history of herpes simplex virus (HSV) episodes was associated with disease activity, while an elevated incidence of anti-CCP2 autoantibody characterized eRA patients with a history of viral upper respiratory tract infection symptoms (V-URI). Granulocyte ROS activity in eRA patients was quantitatively [STZ peak and its area under the curve (AUC)] and qualitatively (STZ time of peak) altered, positively correlated with disease activity, and parameters were associated with viral symptoms including HSV exacerbation/recurrence, and V-URI. In conclusion, our study provides arguments to consider a history of increased viral infection symptoms in RA at the early stage and such involvement needs to be studied further.

Highlights

Rheumatoid arthritis (RA) development results from an inappropriate immune response to environmental challenges in genetically predisposed patients
When compared to controls and first-degree relatives (Figure 1A), early stages of rheumatoid arthritis (eRA) patients included in this study had more frequent infection symptoms in the previous year than healthy controls (4.2 ± 0.4 events/year in eRA versus 2.7 ± 0.2 in controls, P = 0.03), but less than what was observed in relatives (6.0 ± 0.4 events/year, P = 0.004 versus eRA, and P < 10−4 versus controls)
As the incidence of B-URI was similar between the three groups, and as the prevalence and incidence of acute bronchitis was modest in relatives and in eRA patients, both parameters were not considered further

Summary

Introduction

Rheumatoid arthritis (RA) development results from an inappropriate immune response to environmental challenges in genetically predisposed patients. The immunological hypothesis proposes that RA development results from an inappropriate immune response to infections, which can lead to loss of tolerance to self-antigens In support of such a hypothesis, up to 40 risk factors have been associated with RA, and a significant part of the genetic contribution is associated with the major histocompatibility complex locus [2]. While on the other hand, the environmental hypothesis proposes that RA development may result from a cumulative effect of microbial/ viral/environmental factors and explains the absence of a single defined pathogen. In this case, environmental factors may be accelerators or protective [3]

Methods

Results

Conclusion