Pulmonary involvement of ANCA-associated vasculitis in adult Chinese patients

Objective The aim of this study was to clarify the clinical characteristics and long-term outcomes of ANCA-associated vasculitis (AAV) patients with pulmonary involvement from a single Chinese cohort. Methods Newly diagnosed AAV patients with pulmonary involvement, as defined by CT, were recruited from January 2010 to June 2020. Clinical data and CT images were collected retrospectively. Baseline CTs were evaluated and re-classified into four categories: interstitial lung disease (ILD), airway involvement (AI), alveolar hemorrhage (AH), and pulmonary granuloma (PG). Results A total of 719 patients were newly diagnosed with AAV, 366 (50.9%) of whom combined with pulmonary involvement at baseline. Among the AAV cases with pulmonary involvement, 55.7% (204/366) had ILD, 16.7% (61/366) had AI alone, 14.8% (54/366) had PG, and 12.8% (47/366) had AH alone. During follow-up of a median duration of 42.0 months, 66/366 (18.0%) patients died, mainly died from infections. Survival, relapse, and infection were all significantly different based on the radiological features. Specifically, the ILD group tends to have a poor long-term prognosis, the PG group is prone to relapse, and the AI group is apt to infection. The AH group has a high risk of both early infection and relapse, thus a poor short-term prognosis. Conclusion AAV patients with diverse radiological features have different clinical characteristics and outcomes. Therefore, the intensity of immunosuppressive therapy must be carefully valued by considering the baseline CT findings among AAV patients with pulmonary involvement.

Variant Type X91+ Chronic Granulomatous Disease: Clinical and Molecular Characterization in a Chinese Cohort

Purpose: We aimed to report the clinical and immunological characteristics of variant type X91+ CGD in a Chinese cohort.Methods: The clinical manifestations and immunological phenotypes of X91+ CGD patients were collected. Dihydrorhodamine (DHR) analysis was performed to evaluate neutrophil function. Gp91phox protein expression was determined by flow cytometry-based extracellular staining with the monoclonal antibody (mAb) 7D5. Results: X91+CGD patients accounted for 8% (7/85) of all patients with GCD. The median onset age in the 7 X91+ CGD patients was 4 months. Six patients received the same BCG vaccine strain, and three had probable BCG infections. Moreover, 4 patients were highly suspected of having Mycobacterium tuberculosis infection. Recurrent infections of the lungs and soft tissues (3/7) were the most common symptoms. Two patients had noninfectious recurrent oral ulcers and received interferon gamma (IFN-γ) treatment afterward. In our cohort, the stimulation index (SI) of the 7 X91+ CGD patients ranged widely from 1.9 to 67.5, while the SI ranged from 1.2 to 35.7 in patents with X910 CGD. The level of SI between these two groups was statistically significant (P<0.05). CYBB mutations associated with X91+CGD were usually located in or near the FAD and NADPH binding domains. Three new X91+ CGD related mutations (c.1462-2 A>T, c.1243C>T and c.925G>A) were identified. Conclusions: Variant type X91+ CGD may have varied severities of clinical manifestations. Moreover, the laboratory findings of X91+ CGD could present with a moderate neutrophil stimulation index. We should deepen our understanding of the X91+ variant CGD to prevent missed diagnosis.

Association Between Perforating Scleral Vessel and Myopic Maculopathy: A Cross-Sectional Study of a Chinese Cohort

Purpose: To investigate the association between perforating scleral vessel (PSV) and different types of myopic maculopathy (MM) in a highly myopic population.Methods: In total, 188 highly myopic eyes (117 participants) were enrolled. Each participant underwent detailed history taking and ocular examinations. Based on fundus photographs and optical coherence tomography, patients were subdivided into the non-MM group and MM group. Based on a new classification system (ATN), MM cases were classified as myopic atrophy maculopathy (MAM), myopic tractional maculopathy (MTM), and myopic neovascular maculopathy (MNM). The number of PSV and the macular choroidal thickness (mChT) were measured.Results: Compared with non-MM group, MM group was characterized by relatively larger age (48.40 vs. 32.34; p &lt; 0.001), longer axial length (AL, 29.72 vs. 27.75, p &lt; 0.001), thinner mChT (52.90 vs. 122.52; p &lt; 0.001), and lower PSV counts (6.73 vs. 9.47, p ≤ 0.001). The non-MM group had higher PSV counts in total area (0–9 mm, 9.47 vs. 6.73, p &lt; 0.001) and perifovea area (3–9 mm, 7.25 vs. 4.71, p &lt; 0.001) compared to the MM group. Univariate and multivariate analyses showed that PSV count had no association with MAM (p = 0.2419) and MTM (p = 0.5678). Total PSV count [odds ratio (OR) 0.78, 95% CI 0.64–0.95, p = 0.0149] and perifovea PSV count (OR 0.80, 95% CI 0.65–0.98, p = 0.0299) were both protective factors for MNM. The stratified analysis revealed that in groups with AL &lt;28 mm, or mChT &lt;50 μm, or mChT ≥100 μm, or eyes with cilioretinal artery, PSV count had no significant association with MNM.Conclusion: Higher PSV counts in perifovea area (3–9 mm centered fovea) and total area (0–9 mm centered fovea) were protective factors for MNM, whereas PSV count had no association with MAM and MTM. These findings may provide novel insights into the mechanisms of pathologic myopia.

Multi-scalar data integration links glomerular angiopoietin-tie signaling pathway activation with progression of diabetic kidney disease

Diabetes is the leading cause of chronic kidney disease. Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of diabetic kidney disease (DKD). In the Clinical Phenotyping and Resource Biobank study, an unbiased, machine learning approach identified a three-marker panel from plasma proteomics which, when added to standard clinical parameters, improved the prediction of outcome of end-stage kidney disease (ESKD) or 40% decline in baseline glomerular filtration rate (GFR) in a discovery DKD group (N=58) and was validated in an independent group (N=68) who also had kidney transcriptomic profiles available. Of the three markers, plasma angiopoietin 2 (ANGPT2) remained significantly associated with composite outcome in 210 Chinese Cohort Study of Chronic Kidney Disease participants with DKD. The glomerular transcriptional Angiopoietin/Tie (ANG-TIE) activation scores, derived from the expression of 154 literature-curated ANG-TIE signaling mediators, positively correlated with plasma ANGPT2 levels and outcome, explained by substantially higher TEK receptor expression in glomeruli and higher ANG-TIE activation scores in endothelial cells in DKD by single cell RNA sequencing. Our work suggests that activation of glomerular ANG-TIE signaling in the kidneys underlies the association of plasma ANGPT2 with disease progression, thereby providing potential targets to prevent DKD progression.