Predictive risk factors before the onset of familial rheumatoid arthritis: the Tatarstan cohort study.

Background: A familial history of rheumatoid arthritis (RA) predisposes an individual to develop RA. This study aimed at investigating factors associated with this conversion from the Tatarstan cohort. Methods: A total of 144 individuals, referred to as pre-RA and at risk for familial RA, were selected 2 years (range: 2-21 years) before conversion to RA and compared to non-converted 328 first-degree relatives (FDR) from RA as assessed after ≥2 years follow-up, and 355 healthy controls were also selected (HC). Preclinical parameters and socio-demographic/individual/HLA genetic factors were analyzed when data were available at the time of enrollment. Results: As compared to FDR and HC groups, pre-RA individuals were characterized before conversion to RA by the presence of arthralgia, severe morning symptoms, a lower educational level, and rural location. An association with the HLA-DRB1 SE risk factor was also retrieved with symmetrical arthralgia and passive smoking. On the contrary, alcohol consumption and childlessness in women were protective and associated with the HLA-DRB1*07:01 locus. Conclusion: Before RA onset, a combination of individual and genetic factors characterized those who are at risk of progressing to RA among those with familial RA relatives.

In seroconverted rheumatoid arthritis patients a multi-reactive anti-herpes IgM profile is associated with disease activity.

Conflicting results have been reported regarding human herpes virus (HHV) reactivation in patients with rheumatoid arthritis (RA). To explore this link, 74 RA patients were selected and compared to 42 first degree relatives (FDR) from probands with RA and 25 healthy controls from the Tatarstan women cohort. The serological analysis was done by testing anti-HSV/CMV/EBV IgM, IgG, plus the IgG avidity index, and completed by evaluating HSV/CMV/EBV DNA by PCR. Results from these analyses reveal: (i) a long lasting infection of HHV in RA, FDR and healthy controls (IgG seroconversion >97%); (ii) an elevated IgM anti-HHV response in seroconverted RA patients which is related to HSV1/2 reactivation (HSV1/2 PCR+); and (iii) a multi-reactive IgM HHV burden profile associated with disease activity (DAS28). In conclusion, HSV1/2 reactivation in seroconverted RA patients is associated with an abnormal anti-HHV immune response, which was reflected in IgM HHV burden, and in activity disease profile.

Prevalence and Incidence of Upper Respiratory Tract Infection Events Are Elevated Prior to the Development of Rheumatoid Arthritis in First-Degree Relatives.

Introduction: The aim of this study was to characterize infection events in a longitudinal cohort of first-degree relatives (FDR) of probands with rheumatoid arthritis (RA) and explore their associations with RA development. To this end, newly diagnosed RA patients (n = 283), unaffected related FDR and age-matched healthy women were ascertained from the Caucasian triple women prospective Tatarstan cohort. Methods: In this cohort initiated in 1997, 26/283 (9.2%) FDR developed RA (incidence: 9.1 cases/1,000/year). At baseline and during the follow-up, information regarding infectious events (prevalence) and their incidence and duration per year were collected from all individuals. Results: Results reveal in the unaffected FDR developing RA subgroup: (i) a higher prevalence and/or incidence at baseline of upper respiratory infections (URI), otitis, tonsillitis, herpes reactivation, and skin infections; (ii) Mycoplasma sp detection was increased during pregnancy; (iii) a peak of infections started in the 3 years preceding RA onset, and thereafter decreased following RA diagnosis and treatment initiation with disease-modifying anti-rheumatic drugs (DMARDs) when considering URI, and acute tonsillitis; (iv) herpes virus reactivation, at baseline, was associated with a higher report of morning stiffness and arthralgia while independent from rheumatoid factors and anti-citrullinated peptide (CCP)2 Ab positivity; and (v) infection events represent an independent environmental factor associated with RA development. Conclusion: In conclusion, an annual increase of respiratory tract infections was found at the pre-clinical stage of RA. This could be due to alterations in the immune system that result in susceptibility to infection, controlled by DMARDs, or that the infectious events predispose to RA.