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Background: CD4+T cells are involved in the pathogenesis of immunoglobulin A nephropathy (IgAN); T helper (Th) 1, Th17 and Th22 cells promote the occurrence and amplification of inflammatory reactions, while regulatory T (Treg) cells produce the opposite effects. However, whether Th9 cells, a subset of CD4+T cells, participate in IgAN development is still unknown. Methods: Human peripheral blood mononuclear cells (PBMCs) were isolated from IgAN patients for Th9 cells detection by flow cytometry. Wild-type (WT) mouse was used to establish an IgAN mouse model while C3aR and C5aR inhibitor treated IgAN mouse. Kidney disease and function was assessed by histology and albumin-to-creatinine ratio. C3aR and C5aR expression was examined by immunohistochemical (IHC) assay. Th9 cell proportions in the blood of IgAN mouse was detected. C3a, C5a and interleukin (IL)-9 levels were tested by ELISA. Moreover, co-culture system between human mesangial cells (HMCs) and CD4+T cells were constructed with or without C3a, C5a and anti-CCL20 mAb stimulation for transwell assay to examine Th9 cell chemotaxis. Results: We observed the numbers of Th9 cell and the levels of IL-9 were increased in IgAN patients and IgAN mice. Furthermore, C3a and C5a level in serum and kidney, C3aR and C5aR expression was increased in IgAN mice compared to WT mice. Most interestingly, C3aR and C5aR inhibitor could reduce kidney damage, Th9 cell numbers and IL-9 levels. We also observed that C3a and C5a enhanced CCL20 production in HMCs. Notably, C3a and C5a also increased the recruitment of Th9 cells and IL-9 levels by HMCs through enhancing the CCL20-CCR6 pathway. Conclusions: Our results support that C3a and C5a increase the production of CCL20 by HMCs and consequently augment Th9 cell recruitment and IL-9 levels, resulting in IgAN exacerbation.

Background: Hematuria is common in myeloperoxidase anti-neutrophil cytoplasmic antibody associated vasculitis (ANCA-MPO). Previous studies have mainly focused on urinary dysmorphic red blood cells and few have reported the clinical significance of isomorphic urinary red blood cells. Therefore, the main aim of this study was to assess the predictive yield  of urinary isomorphic red blood cells for disease severity and renal outcomes in patients with ANCA-MPO associated vasculitis. Methods: A total of 191 patients with ANCA-MPO associated vasculitis with hematuria were retrospectively selected and were divided into two groups (with isomorphic red blood cells versus dysmorphic red blood cells) according to the percentage of isomorphic red blood cells on urinary sediment analysis. Clinical, biological and pathological data at diagnosis were compared. Patients were followed up for a median of 25 months and progression to end-stage kidney disease and death were regarded as main outcome events. Additionally, univariate and multivariate Cox regression models were used to estimate the risk factors for end-stage kidney disease. Results: Out of 191 patients, 115 (60%) had ≥ 70% and 76 (40%) had < 30% urine isomorphic red blood cells. Compared with patients in the dysmorphic red blood cell group, patients in the isomorphic red blood cell group had a significantly lower estimated glomerular filtration rate (eGFR) [10.41 mL/min (IQR 5.84–17.06) versus 12.53 (6.81–29.26); P= 0.026], higher Birmingham Vasculitis Activity Score [16 (IQR 12–18) versus 14 (10–18); P= 0.005] and more often received plasma exchange [40.0% versus 23.7% (P= 0.019)] at diagnosis. Kidney biopsies revealed a higher proportion of patients with glomerular basement membrane fracture in the isomorphic red blood cell group [46.3% versus 22.9% (P= 0.033)]. Furthermore, patients with predominant urinary isomorphic red blood cells were more likely to progress to end-stage kidney disease [63.5% versus 47.4% (P= 0.028)] and had a higher risk of death [31.3% versus 19.7% (P= 0.077)]. The end-stage kidney disease-free survival was lower in patients in the isomorphic red blood cell group (P= 0.024). However, urine isomorphic red blood cells ≥ 70% could not predict the presence of end-stage kidney disease in multivariate Cox analysis. Conclusion: Myeloperoxidase-anti-neutrophil cytoplasmic antibody associated vasculitis patients with predominant urinary isomorphic red blood cells at diagnosis had more severe clinical manifestations and a higher risk of poor renal outcomes. In this respect, urinary isomorphic red blood cells could be viewed as a promising biomarker of ANCA_MPO vasculitis severity and progression. Graphical abstract:

To investigate the characteristics of the achromatic bandwidth of composite achromatic quartz half-wave plates (QHWPs), three kinds of multi-element achromatic QHWPs with central wavelengths at 1000–3000 nm and relative deviation of the maximum phase retardation (Δδ_max) of 1%–5% are discussed. Based on the particle swarm optimization algorithm, the maximum bandwidth of the composite achromatic QHWPs at room temperature is obtained. The results show that the achromatic bandwidth increases with Δδ_max. At the same Δδ_max, the achromatic bandwidth of four-element achromatic QHWPs is larger than that of two- and three-element achromatic QHWPs. The maximum achromatic bandwidth of four-element achromatic QHWPs can reach 2229 nm when Δδ_max is 5%. In addition, the temperature effect on bandwidth in the wavelength range of 300–1500 nm is analyzed, and the maximum bandwidth of temperature insensitive composite achromatic QHWPs is 840 nm. The results provide a great reference for designing achromatic wave plates with broad bandwidths.

In order to obtain a composite achromatic wave plate with adjustable retardation, temperature insensitivity, and achromatic bandwidth of 500 nm, a five-element composite achromatic quartz wave plate is designed based on particle swarm optimization. The total phase retardation can be adjusted by rotating the azimuth angle of the central wave plate. The results show that the total phase retardation is adjustable with the range of 90°–180° when the range of temperature and the achromatic wavelength is −20−80^∘C and 750–1250 nm, respectively. The absolute value of the relative deviation of the maximum phase retardation is less than 3.6%, which meets the design requirements of the wave plate. The temperature insensitivity of the five-element wave plate is better than the three- and four-element wave plates. This method is of great reference value for designing this kind of composite achromatic wave plate.

Background: Effector memory T cells are pivotal effectors of adaptive immunity with enhanced migration characteristics and are involved in the pathogenesis of ANCA-associated vasculitis (AAV). The diversity of effector memory T cells in chemokine receptor expression has been well studied in proteinase 3 (PR3)-AAV. However, few studies have been conducted in myeloperoxidase (MPO)-AAV. Here, we characterized chemokine receptor expression on effector memory T cells from patients with active MPO-AAV. Methods: Clinical data from newly diagnosed MPO-AAV patients and healthy subjects were collected and analyzed. Human peripheral blood mononuclear cells (PBMCs) isolated from patients with active MPO-AAV were analyzed by flow cytometry. The production of effector memory T cell-related chemokines in serum was assessed by ELISA. Results: We observed decreased percentages of CD4+and CD8+T cells in the peripheral blood, accompanied by a significant decrease in CCR6-expressing T cells but an increase in CXCR3+T cells, in active MPO-AAV. Furthermore, the decrease in CCR6 and increase in CXCR3 expression were mainly limited to effector memory T cells. Consistent with this finding, the serum level of CCL20 was increased. In addition, a decreasing trend in the TEM17 cell frequency, with concomitant increases in the frequencies of CD4+TEM1 and CD4+TEM17.1 cells, was observed when T cell functional subsets were defined by chemokine receptor expression. Moreover, the proportions of peripheral CD8+T cells and CD4+TEMsubsets were correlated with renal prognosis and inflammatory markers. Conclusions: Our data indicate that dysregulated chemokine receptor expression on CD4+and CD8+effector memory T cells and aberrant distribution of functional CD4+T cell subsets in patients with active MPO-AAV have critical roles related to kidney survival.