Joong Kyong Ahn, M.D., Ph.D.. J Rheum Dis 2023;30:88-98. https://doi.org/10.4078/jrd.2022.0001

Objectives. To investigate the effect of α-defensin-1 on the expression of IL-6, IL-8 and MMPs as well as the signal transduction mechanisms responsible for their expression in RA fibroblast-like synoviocytes (FLS). Methods. The concentrations of α-defensin-1 in SF were measured by ELISA. In RA FLS, mRNA expression of IL-6, IL-8 and MMPs and activation of signalling molecules were examined by real-time PCR, western blotting and electrophoretic mobility shift assay. Results. Concentrations of SF α-defensin-1 were significantly increased in RA patients compared with OA patients. The levels of mRNA expression of IL-6, IL-8, MMP-1 and MMP-3 were significantly increased in RA FLS treated with α-defensin-1 compared with controls. Furthermore, α-defensin-1 activated JNK and ERK in RA FLS, respectively. Treatment of RA FLS with ERK or JNK inhibitors prior to α-defensin-1 treatment resulted in reduced expression of IL-6, IL-8, MMP-1, and MMP-3 compared with controls. Remarkably, treatment of RA FLS with an ERK inhibitor prior to α-defensin-1 stimulation significantly reduced production of IL-6 and MMP-1 by approximately 71% and 98% compared with controls, respectively. The JNK inhibitor significantly suppressed α-defensin-1-induced MMP-1 production by approximately 73% compared with controls. Finally, there was a significant induction of NF-κB DNA binding activity in response to α-defensin-1. Conclusion. Our results suggest that α-defensin-1 may play a role in RA pathogenesis by regulating the production of MMPs as well as IL-6 and IL-8. These processes were dependent on the regulation of the JNK and/or ERK and NF-κB pathways.

Diagnosing Behcet’s disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight–mass spectrometry (GC/TOF−MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF−MS, in conjunction with multivariate statistical analysis. A total of 110 urinary metabolites were identified. The urine metabolite profiles obtained from GC/TOF−MS analysis could distinguish BD patients from the HC group in the discovery set. The parameter values of the orthogonal partial least squared-discrimination analysis (OPLS-DA) model were R²X of 0.231, R²Y of 0.804, and Q² of 0.598. A biomarker panel composed of guanine, pyrrole-2-carboxylate, 3-hydroxypyridine, mannose, l-citrulline, galactonate, isothreonate, sedoheptuloses, hypoxanthine, and gluconic acid lactone were selected and adequately validated as putative biomarkers of BD (sensitivity 96.7%, specificity 93.3%, area under the curve 0.974). OPLS-DA showed clear discrimination of BD and HC groups by a biomarker panel of ten metabolites in the independent set (accuracy 88%). We demonstrated characteristic urinary metabolic profiles and potential urinary metabolite biomarkers that have clinical value in the diagnosis of BD using GC/TOF−MS.

Objectives: To determine whether level of serum uric acid (SUA) is linked to pulmonary function in health screening examinees without overt medical conditions. Methods: We performed a cross-sectional study on 69,928 Koreans that participated in an annual health check. Results: Percent predicted forced vital capacity (FVC%) and forced expiratory volume in 1 s (FEV1%) were positively correlated with SUA in both genders (FVC%: r = .361; FEV1%: r = .314 in males and FVC%: r = .413; FEV1%: r = .382 in females, all p < .001). When the 2nd, 3rd and lowest FEV1% quartile were compared to the highest quartile group (the reference) by regression analysis, the adjusted ORs for hyperuricemia in males were 0.876 (95% CI, 0.809–0.949), 0.631 (0.574–0.695), and 0.311 (0.278–0.349), respectively. The adjusted ORs for hyperuricemia when the 2nd, 3rd and lowest FEV1% quartile were compared to the highest quartile in males were 0.791 (95% CI, 0.729–0.859), 0.565 (0.513–0.623), and 0.302 (0.270–0.337), respectively (p for trend <.001). Similarly, the adjusted OR of having hyperuricemia in females decreased significantly across FEV1% and FVC% quartile groups compared to the reference. Conclusions: Hyperuricemia may have a positive effect on pulmonary function in middle aged healthy population.