Background/Objectives: Patients with rheumatoid arthritis (RA) are prone to develop infections. Methods: Accordingly, 195 untreated early (e)RA patients and 398 healthy controls were selected from women in Tatarstan’s cohort to study infectious history in the anamnesis (four criteria) and in the previous year (16 criteria). Information about annual infections was collected face-to-face from year to year by a qualified rheumatologist/general practitioner and included the active use of information from medical records. Results: In the anamnesis, tuberculosis, and pneumonia, and in the previous year, respiratory tract infections, skin infections, and herpes simplex virus reactivation incidence were reported to be increased in eRA patients, as well as the event number and duration of acute and chronic tonsillitis. Moreover, more bacterial-suspected upper respiratory infections and urinary tract infections were retrieved in sporadic eRA patients as compared to familial eRA patients. An elevated immunization against CCP prevented respiratory tract infection in those with HSV exacerbation. Finally, associations were retrieved between infection (event number/delay) and RA indices: (i) chronic tonsillitis exacerbations with disease activity and health assessment (HAQ) in familial eRA; (ii) bacterial-suspected upper respiratory infections with the number of swollen and tender joints in sporadic eRA; and (iii) HSV exacerbation with inflammation in eRA patients with negative/low response against CCP. Here, we demonstrate the complex nature of the interplay of RA with specific infections. Conclusions: For the first time, differences in the patterns of annual trivial infections and their links with RA indices were found in cohorts of familial and sporadic cases of the disease. Additionally, for the first time, we identified a remarkable relationship between early RA and exacerbations of chronic tonsillitis, as well as tuberculosis in the patient’s history. Altogether, this study supports the existence of a complex interplay between infections and RA at onset driven by familial status and the presence of anti-CCP Ab at elevated levels.

Environmental factors are suspected of triggering rheumatoid arthritis (RA). One such factor is oxidative stress (OS), which is a step in ecotoxin detoxification and a damaging factor. The linkage of ecotoxin-triggered OS with clinical and laboratory RA indices in patients and individuals at the pre-RA stage was studied in patients with early (e) (n = 35) and advanced (a) stages of RA (n = 25) and individuals at pre-RA stages (FDR-First-Degree Relative(s), pre-RA, n = 72) in comparison with 52 healthy individuals without autoimmune and immunoinflammatory diseases in their family history (Controls). Ecotoxins within permissible concentration limits were associated with serum levels of OS markers in all cohorts, including Controls. Serum oxidized low-density lipoprotein (oxLDL) levels in pre-RA and eRA cohorts exceeded Control values. Significant differences were found in anti-oxLDL antibody correlations and OS markers. In pre-RA and both RA cohorts, a relationship was found with regards to serum antibodies to cyclic citrullinated peptide (ACCP) levels. Thus, ecotoxin-induced OS likely triggers pathogenic mechanisms at the pre-RA stage and RA onset.

BACKGROUND: Rheumatoid arthritis (RA) is a phenotypically heterogeneous disease. AIM: The study aimed to identify the role of triggers in the onset of RA and preclinical joint symptoms, as well as their association with clinical and laboratory parameters. METHODS: Data on potential disease triggers and preclinical joint symptoms were collected from patients with early RA (n = 461) and their relatives (n = 247). Moreover, 299 healthy participants (control group) were examined for past infections within the previous 6–12 months. Anxiety levels, number of childbirths, age at onset of menopause, and body mass index (BMI) were assessed. Additionally, the association of triggers with composite disease activity indices, morning stiffness duration, severity of functional joint impairment, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) levels, anti-citrullinated peptide antibodies (ACPA), and rheumatoid factor (RF) was assessed. Data were analyzed using the Mann–Whitney test, multiple regression analysis, and Spearman correlation. RESULTS: The most common triggers for RA and preclinical joint symptoms were menopause (17.6%, 11.7%), infections (13.4%, 15.8%), and psychological stress (15.2%, 18.2%). Preclinical joint symptoms were additionally provoked by physical exertion (19.8%). RA triggered by infections or menopause was associated with an increased frequency and duration of infections (p 0.001) and higher BMI (p = 0.019 and p = 0.024, respectively) compared with controls. A similar association was observed between preclinical joint symptoms triggered by infections and increased frequency and duration of infections (p 0.001). Additionally, joint symptoms triggered by physical exertion were associated with more frequent and prolonged infections compared with the control group (p = 0.015 and p = 0.016, respectively). ESR levels exhibited a heightened response when preclinical joint symptoms were associated with infections (p = 0.010), menopause (p = 0.033), or physical exertion (p = 0.020) in comparison with their response to psychological stress. The arthralgia score was highest when provoked by menopause compared with cases provoked by infection (p = 0.053) or childbirth (p = 0.012). Preclinical joint symptoms triggered by psychological stress were associated with a higher arthralgia score than those provoked by physical exertion (p = 0.002). In the preclinical group, ESR and CRP levels correlated with BMI (p = 0.005 and p = 0.028, respectively). In patients with RA, ACPA (p = 0.044) and RF (p = 0.009) concentrations were associated with personal anxiety levels. CONCLUSION: The influence of triggers on clinical and laboratory parameters is evident in preclinical RA. The highest arthralgia scores were observed in cases triggered by menopause or psychological stress. Joint symptoms associated with infections, menopause, or physical exertion were associated with higher ESR levels.

Rheumatoid arthritis (RA) is a multifactorial disease. Environmental toxins are among its suspected triggers. Objective. The aim of the study is to examine the correlation between environmental parameters and clinical and laboratory parameters in patients with RA and individuals with pre-RA. Materials and Methods. The study enrolled four groups of patients with early (early RA, n=349), established (established RA, n=529), and preclinical (pre-RA, n=333) stages of RA, as well as presumably healthy individuals with no family history of autoimmune and immuno-inflammatory diseases (control, n=203). The authors analyzed the correlation between clinical signs and laboratory parameters of RA with 10-year average environmental parameters in the administrative districts of the Republic of Tatarstan (RT) and heavy metal concentrations in soil samples from the residential areas of the study participants. Results. Environmental factors at maximum permissible concentrations (MPCs) influenced some key parameters in all groups, including the control one, particularly RF and ESR. Furthermore, environmental factors also affected serum Ig levels in the combined cohort of all subjects examined, and these parameters were inversely proportional to environmental toxicant levels. Undeniable evidence of the environmental factor impact on immunopathological processes at pre-RA stages is the identified pattern: unlike patients with pre-RA (stages III and VI) and those with early RA (stage V), patients with RA stage I (genetic) predominate in areas with lower population density and lower concentrations of certain air pollutants. Further evidence of the involvement of environmental factors in the immunopathogenesis of pre-RA and the disease itself is the identified correlation between clinical and laboratory parameters of RA in the pre-RA and early RA groups. Conclusion. Correlation between environmental factors and clinical/laboratory parameters was demonstrated in all study groups. The obtained data on the role of environmental factors in RA pathogenesis can be used to develop therapeutic intervention algorithms aimed at preventing or delaying the disease onset at its preclinical stage.