Tobacco-Derived Lipopolysaccharide, Not Microbial Translocation, as a Potential Contributor to the Pathogenesis of Rheumatoid Arthritis

Abstract

Microbial lipopolysaccharides (LPS) have been implicated in the pathogenesis of rheumatoid arthritis (RA), possibly driving a systemic inflammatory response that may trigger the development and/or exacerbation of the disease. To explore the existence of this mechanism in African RA patients, we have measured systemic levels of LPS and its surrogate, LPS-binding protein (LBP), as well as those of intestinal fatty acid-binding protein (I-FABP), pulmonary surfactant protein D (SP-D), and cotinine in serum to identify possible origins of LPS, as well as associations of these biomarkers with rheumatoid factor (RF) and anticitrullinated peptide (aCCP) autoantibodies and the DAS 28-3 clinical disease severity score. A cohort of 40 disease-modifying antirheumatic drug-naïve, black South African RA patients rated by compound disease scores and 20 healthy subjects and 10 patients with chronic obstructive pulmonary disease (COPD) as controls were included in this study. Levels of the various biomarkers and autoantibodies were measured using a combination of ELISA and immunofluorimetric and immunoturbidometric procedures. LPS levels were lowest in the RA group compared to the healthy controls (p = 0.026) and COPD patients (p = 0.017), while LBP levels were also significantly lower in RA compared to the healthy individuals (p = 0.036). Levels of I-FABP and SP-D were comparable between all three groups. Categorisation of RA patients according to tobacco usage revealed the following significant positive correlations: LBP with C-reactive protein (p = 0.0137); a trend (p = 0.073) towards an association of LBP with the DAS 28-3 disease severity score; RF-IgG antibodies with both LPS and LBP (p = 0.033 and p = 0.041, respectively); aCCP-IgG antibodies with LPS (p = 0.044); and aCCP-IgG with RF-IgM autoantibodies (p = 0.0016). The findings of this study, several of them novel, imply that tobacco products, as opposed to microbial translocation, represent a potential source of LPS in this study cohort of RA patients, again underscoring the risks posed by tobacco usage for the development and severity of RA.

A Shifted Urinary Microbiota Associated with Disease Activity and Immune Responses in Rheumatoid Arthritis

“…Here, we reveal that the RA-related urinary microbiota displayed close correlations with host systemic immune responses; we found that increased amounts of Rhizorhapis , Stenotrophomonas , and Alcaligenes in RA patients were positively associated with plasma cells, serum LBP, and/or sCD14, with the latter being involved in the recognition of pathogenic bacteria and enhancement of LPS-mediated cytokine induction ( 25 – 27 ). The two inflammatory factors were linked to a number of inflammatory conditions, including RA, and positively correlated with RA disease activity ( 26 – 29 ). In addition, certain urinary microbes were associated with MAIT cells, which are innate-like T cells able to recognize bacterial metabolites presented by major histocompatibility complex (MHC) class I-related protein 1 (MR1) ( 30 ).…”

Effects of betulinic acid on synovial inflammation in rats with collagen-induced arthritis

“…The separated synovial tissues were soaked in phosphate-buffered saline (PBS) for 5 min, rinsed with PBS, and placed in a Petri dish. Tissues were minced and digested by adding type II collagenase (2 mg·mL − 1 ) was suspended in Dulbecco’s modified Eagle’s medium (DMEM) containing 10% fetal bovine serum (FBS; Cat. #10099-141, Gibco, Life Technologies Corporation, Beijing, China).…”

“…Rheumatoid arthritis (RA) is a systemic autoimmune disease, and is the most common inflammatory joint disease affecting 1% of the world’s population. 1 If RA is not actively treated at an early stage, it gradually progresses and leads to the destruction of joints and their loss of function. This reduces the patient’s quality of life and can even result in disability.…”

Liquiritigenin, isoliquiritigenin rich extract of glycyrrhiza glabra roots attenuates inflammation in macrophages and collagen-induced arthritis in rats

“…(Roe, 2021). Rheumatoid arthritis (RA) is a progressive autoimmune joint disease caused by environmental and genetic factors (Meyer et al, 2019). The yearly occurrence of RA is approximately three in ten thousand people, increasing with age and peaking between 35 and 50 years (Gabriel, 2001).…”