No genetic causal association between iron status and pulmonary artery hypertension: Insights from a two-sample Mendelian randomization.

To explore the genetic causal association between pulmonary artery hypertension (PAH) and iron status through Mendelian randomization (MR), we conducted MR analysis using publicly available genome-wide association study (GWAS) summary data. Five indicators related to iron status (serum iron, ferritin, total iron binding capacity (TIBC), soluble transferrin receptor (sTfR), and transferrin saturation) served as exposures, while PAH was the outcome. The genetic causal association between these iron status indicators and PAH was assessed using the inverse variance weighted (IVW) method. Cochran's Q statistic was employed to evaluate heterogeneity. We assessed pleiotropy using MR-Egger regression and MR-Presso test. Additionally, we validated our results using the Weighted median, Simple mode, and Weighted mode methods. Based on the IVW method, we found no causal association between iron status (serum iron, ferritin, TIBC, sTfR, and transferrin saturation) and PAH (p ß > 0.05). The Weighted median, Simple mode, and Weighted mode methods showed no potential genetic causal association (p ß > 0.05 in the three analyses). Additionally, no heterogeneity or horizontal pleiotropy was detected in any of the analyses. Our results show that there are no genetic causal association between iron status and PAH.

CD4/CD8 Ratio: An Independent Predictor of Herpes Zoster in Patients With Autoimmune Inflammatory Rheumatic Diseases.

BACKGROUND: A higher incidence of herpes zoster (HZ) was found in people with decreased cell-mediated immunity. However, the relationship between cellular immunity and HZ infection in patients with autoimmune inflammatory rheumatic diseases (AIRD) remains elusive. OBJECTIVE: To investigate the role of CD4/CD8 ratio in patients with AIRD and HZ. METHODS: This case-control study compared AIRD patients with and without HZ. We chose 70 AIRD patients with HZ as the experimental group and 140 AIRD patients without HZ as the control group. The clinical and laboratory findings were assessed in each trial participant. RESULTS: The CD4/CD8 ratio (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.10-0.49) was independently associated with the occurrence of HZ after adjusting for various confounders. Nonlinear analysis has unveiled a more profound nonlinear relationship between the CD4/CD8 ratio and the occurrence of HZ in patients with AIRD. The OR of HZ increased with a decreasing CD4/CD8 ratio before the turning point of 2. The adjusted regression coefficient was 0.14 (95% CI, 0.05-0.37, p<0.0001) for CD4/CD8 ratio less than 2. CONCLUSION: The CD4/CD8 ratio was expected to be a very promising quantitative biomarker for predicting the risk of developing HZ in patients with AIRD.

Effect of hydroxychloroquine blood concentration on the efficacy and ocular toxicity of systemic lupus erythematosus.

In the absence of evidence-based guidance on the impact of hydroxychloroquine (HCQ) blood concentration on efficacy and ocular toxicity in systemic lupus erythematosus (SLE), the clinical monitoring of HCQ blood concentration is not yet widely performed, which raised concerns about the necessity of conducting HCQ blood concentration monitoring. In this retrospective study, we consecutively enrolled 135 patients with SLE who received HCQ treatment for more than 6 months from July 2022 to December 2022. Ocular toxicity was evaluated by collecting relevant retinal parameters using optical coherence tomography angiography (OCTA). Therapeutic efficacy was evaluated using the SLE disease activity index (SLEDAI) and relevant clinical parameters. HCQ blood concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Spearman correlation analysis revealed that the cumulative dose of HCQ was positively correlated with the foveal avascular zone (FAZ) perimeter and FAZ area (r = 0.734, P < 0.001; r = 0.784, P < 0.001). Meanwhile, the treatment duration of HCQ was positively correlated with FAZ perimeter and FAZ area (r = 0.761, P < 0.001; r = 0.882, P < 0.001). The univariate and multivariate logistic regression analyses indicated that HCQ blood concentration was associated with the disease activity of patients with SLE (odds ratio 0.994, 95% CI 0.990-0.999). HCQ blood concentration may be an important factor in assessing the therapeutic effectiveness of SLE patients. The HCQ-related ocular toxicity was a long-term effect related to long term exposure, rather than the blood concentration of HCQ at the time of testing. More importantly, when addressing HCQ-related ocular toxicity, it may be crucial to pay attention to the cumulative dose and treatment duration of HCQ.

Factors affecting different COVID-19 outcomes in patients with systemic lupus erythematosus during the second pandemic wave of COVID-19 in China.

OBJECTIVE: To investigate characteristics associated with different COVID-19 outcomes of people with systemic lupus erythematosus (SLE) and COVID-19 during the second pandemic wave of COVID-19 in China. METHODS: In this retrospective study, people with SLE and COVID-19 who visited the First Affiliated Hospital of Nanchang University from December 2022 and February 2023 were subjected to this study. The three possible outcomes were listed in order of ordinal severity: (1) not hospitalized, (2) hospitalized but not receiving oxygenation, and (3) hospitalized with any ventilation or oxygenation. A multivariable ordinal logistic regression model was built to examine the association between COVID-19 severity and demographic traits, medications, comorbidities, and disease activity. Furthermore, among the 301 SLE patients included in our study, only two patients experienced mortality. In order to maintain statistical rigor, we have included these two deceased patients in the outcome measure of hospitalized with any ventilation or oxygenation. RESULTS: A total of 301 patients with SLE were enrolled in this study. The multivariate ordinal logistic regression analyses indicated that high SLE disease activity (vs remission; OR 39.04, 95% CI 3.08 to 494.44, p = .005) was associated with more severe outcomes. Three doses of COVID-19 vaccination (OR 0.19, 95% CI 0.07 to 0.51, p = .001), glucocorticoids dose (1-5 mg/day 0.14, 0.03 to 0.73, p = .020, and 6-9 mg/day 0.12, 0.02 to 0.61, p = .010), and more intensive immunosuppression drugs (0.34, 0.12 to 0.97, p = .044) were associated with better outcomes. In age-adjusted and sex-adjusted models, telitacicept (6.66, 1.35 to 32.86, p = .020) and rituximab (7.81, 1.87 to 32.66, p = .005) were associated with more severe outcomes. Hydroxychloroquine (0.47, 0.25 to 0.88, p = .018) was associated with favorable outcomes. CONCLUSION: Different COVID-19 outcomes in people with SLE are mostly driven by COVID-19 vaccination, medications, and activity SLE. More importantly, three doses of COVID-19 vaccination may be associated with better outcomes.

Performance of eye sign combined with increased interleukin-6 in cerebrospinal fluid in patients with neuropsychiatric lupus erythematosus.

OBJECTIVES: To ascertain whether microvascular alterations of eye sign combined with intrathecal concentrations of interleukin-6 (IL-6) can predict the development of neuropsychiatric systemic lupus erythematosus (NPSLE). METHODS: Cerebrospinal fluid (CSF) and serum samples of IL-6 were collected and measured at the same time for patients with SLE who were consecutively enrolled. Patients with a diagnosis of NPSLE were identified. Eye sign examinations according to our criteria were performed and scored for all SLE patients. Demographic and clinical parameters were compared between groups to identify potential predictors for NPSLE using multivariable logistic regression analysis. The performance of potential predictors from eye sign along with IL-6 in the CSF was assessed. RESULTS: A total of 120 patients with SLE were enrolled; 30 with NPSLE and 90 with non-NPSLE. No significant positive correlation was observed between CSF level and serum level of IL-6. CSF IL-6 was significant higher in the NPSLE group than the non-NPSLE (P < 0.001) group. Multivariable logistic analysis revealed that total score, ramified loops, and microangioma of eye sign were predictors for NPSLE after adjusting for SLE Disease Activity Index (SLEDAI) and antiphospholipid antibody (APL). Total score, ramified loops, microangioma of eye sign, and SLEDAI remain significant predictors for NPSLE after adjusting for CSF IL-6. Using receiver operating characteristics curve analysis, the cut-off point of potential predictors was applied in multivariable logistic analysis; APL, total score, ramified loops, and microangioma of eye sign remain significant predictors for NPSLE after adjusting for CSF IL-6. CONCLUSION: Specific microvascular alterations of eye sign are predictors for the development of NPSLE in addition to increased IL-6 in the CSF.

Overexpression of regulatory T cells in patients with unexplained recurrent pregnancy loss: friend or foe?

Background: This study aimed to investigate the role of regulatory T cells in patients with unexplained recurrent pregnancy loss (URPL). Methods: We retrospectively analyzed 136 women who had experienced two or more miscarriages before 24 weeks of gestation for no obvious reason from May 2018 to October 2021. The basic clinical data of the patients and expression of lymphocyte subsets such as regulatory T cells (Tregs) and natural killer cells (NKs) by flow cytometry were collected to explore the risk factors of pregnancy outcome in URPL patients. Results: A total of 136 URPL patients were enrolled in this study. Eventually, 50 patients attained clinical pregnancy. The median age was 31.8 ± 4.6 years in patients with clinical pregnancy. The univariate and multivariate logistic regression analyses indicated that Tregs was associated with the pregnancy outcomes of patients with URPL (odds ratio 0.63, 95% confidence interval 0.50-0.80). More importantly, a U-shaped association was found between Tregs and pregnancy outcome (p < 0.001), with either higher or lower Tregs levels adversely affecting pregnancy outcome. Conclusion: Tregs levels that are either too high or too low can harm pregnancy outcomes. It was expected to be a very promising quantitative biomarker for predicting pregnancy outcomes in URPL patients.