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

BackgroundA 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.MethodsA 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.ResultsAs 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.ConclusionBefore 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

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

Toxoplasma gondii seroprevalence in goats, cats and humans in Russia

The findings suggest that the natural environment in Russia may be widely polluted with T. gondii oocysts shed by cats, and ingestion of these oocysts provides a major route for human infection with this parasite

Editorial: Epigenetic aspects of autoimmune diseases

International audienceGenetics, environmental factors, and epigenetics all contribute to autoimmune disease onset and progression (Gulati and Brunner, 2018). Most of the earlier research on autoimmune diseases focused on genetics and environmental factors. Research into genetics, in attempting to identify specific risk alleles has had limited success, for example, identifying HLA-DRB1, a complex of genes coding for cell surface proteins, has emerged as a risk allele for autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) (Niu et al., 2015). However, genetic findings have not been sufficient to explain the majority of RA and SLE cases, autoimmune diseases in general, or the typical delay in initial onset, occurring later in life (early to mid-adulthood), in most autoimmune diseases. Even with identification of a risk allele, it is not clear if it is a cause of the disease or just a subsidiary factor. Likewise, environmental factors (e.g., viruses, toxins, bacteria, etc.) also present confusion as to their role since a variety of environmental factors and combinations can be involved in triggering onset of an autoimmune disease (Arleevskaya et al., 2016; Arleevskaya et al., 2020). For example, Epstein-Barr virus (EBV) is suspected of a role in autoimmune diseases, especially multiple sclerosis (MS) (Bjornevik et al., 2022). However, almost all adults have had exposure to EBV but only a small percentage develop MS and onset can be many years after initial infection with EBV. It may be that another environmental factor and/or a genetic risk allele needs to be involved, such as an especially heavy cellular viral load of EBV that may occur by viral binding and entry using HLA-DR cell surface proteins as opposed to other HLA types (Agostini et al., 2018). Research into the involvement of epigenetics in autoimmune diseases has been steadily increasing in the past two decades. Epigenetics is the control of gene expression or suppression without changing the underlying DNA sequence of the gene (Renaudineau et al., 2011). Epigenetics can involve methylation of DNA, which typically suppresses the underlying gene, or demethylation of the DNA as a step towards expression (Fali et al., 2014). Coordinated with the DNA methylation state ar

Serological herpes infection burden is associated with diseases activity in rheumatoid arthritis

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Microbes and Viruses Are Bugging the Gut in Celiac Disease. Are They Friends or Foes?

The links between microorganisms/viruses and autoimmunity are complex and multidirectional. A huge number of studies demonstrated the triggering impact of microbes and viruses as the major environmental factors on the autoimmune and inflammatory diseases. However, growing evidences suggest that infectious agents can also play a protective role or even abrogate these processes. This protective crosstalk between microbes/viruses and us might represent a mutual beneficial equilibrium relationship between two cohabiting ecosystems. The protective pathways might involve post-translational modification of proteins, decreased intestinal permeability, Th1 to Th2 immune shift, induction of apoptosis, auto-aggressive cells relocation from the target organ, immunosuppressive extracellular vesicles and down regulation of auto-reactive cells by the microbial derived proteins. Our analysis demonstrates that the interaction of the microorganisms/viruses and celiac disease (CD) is always a set of multidirectional processes. A deeper inquiry into the CD interplay with Herpes viruses and Helicobacter pylori demonstrates that the role of these infections, suggested to be potential CD protectors, is not as controversial as for the other infectious agents. The outcome of these interactions might be due to a balance between these multidirectional processes

Effects of environmental factors and omega-3 fatty acids on rheumatoid arthritis.

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Microbial and Environmental Factors in Autoimmune and Inflammatory Diseases

In recent years there has been a substantial increase in the number of diseases with the inflammatory component such as such as allergy, asthma, rheumatoid arthritis, inflammatory bowl disease (IBD, which includes ulcerative colitis and Crohn's disease), chronic sinusitis, and many other conditions. The majority of these diseases are multifactorial, with the contribution of genetic and environmental factors. Among the latter, the role of certain microorganisms and viruses in triggering or sustaining the inflammatory process is most controversial. In rheumatoid arthritis, for example, the following bacteria and viruses have been implicated in triggering the disease: Mycoplasma spp., Proteus mirabilis, Escherichia coli, Staphylococcus spp., Bordetella spp., Acinetobacter spp., the parvoviruses, Epstein-Barr virus, and retroviruses. The list of putative microbial triggers of rheumatoid arthritis is still growing, and it becomes essentially impossible to make a causation link between certain infectious agents and the disease. In the light of these disappointing results there are calls for even larger studies with the use of more advanced and large-scale technologies. The primary function of the immune system is the maintenance of body homeostasis and protection against any threats to it via several lines of elaborate and complex immune defense. Given even higher complexity that involves the microbiota and the corresponding host-microbe interaction, the conditions for this equilibrium become even more challenging. In the absence of a defined pathogen, for example, the spectrum of microorganisms involved in triggering inappropriate immune responses may include polymicrobial communities or the cumulative effect of several microbial/viral factors. Under the normal circumstances there is a fine-tuned balance between commensal microbiota and the host’s immune responses. However, when this balance is compromised, for example in IBD, a massive immune response is launched against commensal microbiota resulting in chronic inflammation. Besides the microbial/viral factors, the balance of the immune system can be compromised by other causes. Given, for example, the close and inclusive interaction of the immune, nervous and endocrine systems, the list of these provoking factors can expand even more. For instance, it has been demonstrated that even mild sleep deprivation may increase the production of interleukin-6 and C-reactive protein. Understanding the complex role of microbial and environmental factors in inflammatory and autoimmune diseases, therefore, is the main subject of this topic