Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients.

BACKGROUND/OBJECTIVE: Chronic humoral immune response against multiple microbial antigens may play a crucial role in the etiopathogenesis of rheumatoid arthritis (RA). We aimed to assess the prevalence and magnitude of antibody response against various bacterial and viral immunogen peptides in the sera of RA patients compared with the general population. METHODS: Polyclonal IgG antibodies (Abs) specific for peptides derived from Porphyromonas gingivalis (RgpA, Kpg), Aggregatibacter actinomycetemcomitans (LtxA1, LtxA2), Mycobacterium avium subsp. paratuberculosis (MAP4027), Epstein-Barr virus (EBNA1, EBVBOLF), and human endogenous retrovirus (HERV-W env-su) were detected by ELISA in serum samples from 148 consecutive RA patients and 148 sex and age-matched healthy controls (HCs). In addition, the presence of a relationship between the positivity and the titer of antibodies and RA descriptors was explored by bivariate correlation analysis. RESULTS: RA patients exhibit a higher prevalence of humoral immune response against all tested peptides compared to HCs with a statically significant difference for MAP4027 (30.4% vs. 10.1%), BOLF (25.7% vs. 8.1%), RgpA (24.3% vs. 9.4%), HERV W-env (20.3% vs. 9.4%), and EBNA1 (18.9% vs. 9.4%) peptides. Fifty-three (35.8%) out of 148 RA serum and 93 (62.8%) out of 148 HCs were negative for all pathogen-derived peptides. There was a significant correlation between OD values obtained by ELISA test against all peptides (p < 0.0001). We also found an increased titer and prevalence of Abs against LtxA1 and LtxA2 in seropositive vs. seronegative RF (p = 0.019, p = 0.018). CONCLUSION: This study demonstrates a significantly increased humoral response against multiple pathogens in patients with RA and implies that they could be an important factor in the pathogenesis of the disease. Therefore, the role of each individual pathogen in RA needs to be further investigated.

Methotrexate therapy is not associated with increased liver stiffness and significant liver fibrosis in rheumatoid arthritis patients: A cross-sectional controlled study with real-time two-dimensional shear wave elastography.

OBJECTIVE: To explore the significance of the association between treatment with methotrexate (MTX) and liver stiffness in rheumatoid arthritis (RA) patients. METHODS: We enrolled 140 consecutive RA patients under MTX treatment (MTX-treated RA; mean treatment duration: 6.2 years; mean MTX cumulative dose: 4.67 g), 33 RA patients naive to MTX (MTX-naive RA) and 100 age and sex-matched healthy blood donors (HD). Liver stiffness was assessed by real time two-dimensional shear wave elastography, with values ≥7.1 Kilopascals (kPa) defining significant liver fibrosis. RESULTS: kPa values in HD (4.32 ±â€¯0.7) were lower than that in MTX-naive RA (4.92 ±â€¯0.8) and MTX-treated RA (4.85 ±â€¯0.9, p < .0005 for trend). On the contrary, the difference in kPa between MTX-naive and MTX-treated RA was not significant (p = .89). Similarly, liver stiffness was not significantly different across strata of cumulative MTX dose (4.95 ±â€¯0.7 kPa in MTX <1 g, 4.90 ±â€¯1.1 kPa in MTX 1-3 g and 4.80 ±â€¯0.9 in MTX >3 g, p = .610). Significant liver fibrosis was diagnosed in 4 patients in the MTX-treated RA (highest kPa value = 7.6; no liver function test abnormalities or clinical signs of hepatic failure) and in none in both the MTX-naive RA and HD groups (p = .145). CONCLUSION: Liver stiffness values, although within the normal range, are significantly higher in RA patients vs. controls, irrespective of MTX treatment. RA patients taking MTX do not have a higher prevalence of significant liver fibrosis when compared to MTX naive RA patients and the general population.

Prevalence and Determinants of Peripheral Microvascular Endothelial Dysfunction in Rheumatoid Arthritis Patients: A Multicenter Cross-Sectional Study.

OBJECTIVES: To define the prevalence and determinants of peripheral microvascular endothelial dysfunction (ED) in a large series of rheumatoid arthritis (RA) patients free of previous cardiovascular events. MATERIALS AND METHODS: Data from 874 RA patients enrolled in the EDRA study (Endothelial Dysfunction Evaluation for Coronary Heart Disease Risk Estimation in Rheumatoid Arthritis-ClinicalTrials.gov: NCT02341066) were analyzed. Log-transformed reactive hyperemia index (Ln-RHI) was evaluated by peripheral arterial tonometry (PAT) using the EndoPAT2000 device: values of Ln-RHI < 0.51 were considered indicative of peripheral ED. RESULTS: Peripheral microvascular ED was documented in one-third of RA patients (33.5%); in multiple logistic regression analysis, ACPA negativity and higher triglycerides concentrations were independently associated with the presence of peripheral ED [OR (95% CI) = 1.708 (1.218-2.396), p < 0.01 and OR (95% CI) = 1.005 (1.002-1.009), p < 0.01, respectively]. Multiple regression analysis showed a positive correlation between Ln-RHI values and systolic blood pressure and HDL cholesterol levels; furthermore, higher values of Ln-RHI were associated with ACPA positivity, while smoking habit was associated with lower Ln-RHI values. CONCLUSIONS: This study demonstrates for the first time a high prevalence of peripheral microvascular ED in patients with RA free of previous cardiovascular events that appear to be only partially driven by traditional cardiovascular risk factors. The association between ACPA negativity and ED warrants further exploration.