HBx promotes glomerular podocyte-induced immune cell responses.

BACKGROUND: Podocytes, as intrinsic renal cells, can also express MHC-II and costimulatory molecules under inflammatory conditions, suggesting that they may act as antigen-presenting cells (APCs) to activate immune cell responses and then lead to immune-mediated renal injury. They are already recognized as main targets in the pathogenic mechanism of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN). Previous studies also have indicated that inflammatory cells infiltration and immune-mediated tissue injury are evident in the kidney samples of patients with HBV-GN. However, the role of podocytes immune disorder in the pathogenic mechanism of HBV-GN remains unclear. METHODS: Renal function and inflammatory cells infiltration were measured in HBV transgenic (HBV-Tg) mice. In vitro, podocytes/CD4+ T cells or macrophages co-culture system was established. Then, the expression of HBx, CD4, and CD68 was determined by immunohistochemistry, while the expression of MHC-II, CD40, and CD40L was determined by immunofluorescence. Co-stimulatory molecules expression was examined by flow cytometry. The levels of inflammatory factors were detected by ELISA. RESULTS: In vivo, renal function was obviously impaired in HBV-Tg mice. HBx was significantly upregulated and immune cells infiltrated in the glomerulus of HBV-Tg mice. Expression of MHC-II and costimulatory molecule CD40 increased in the podocytes of HBV-Tg mice; CD4+ T cells exhibited increased CD40L expression in glomerulus. In vitro, CD40 expression was markedly elevated in HBx-podocytes. In co-culture systems, HBx-podocytes stimulated CD4+ T cells activation and caused the imbalance between IFN-γ and IL-4. HBx-podocytes also enhanced the adhesion ability of macrophages and induced the release of proinflammatory mediators. CONCLUSION: Taken together, these podocyte-related immune disorder may be involved in the pathogenic mechanism of HBV-GN.

Serum IL-6 as a marker of disease progression in interstitial nephritis.

OBJECTIVE: To investigate the mechanism of serum interleukin-6 (IL-6) change in disease progression of interstitial nephritis. METHODS: This is a retrospective study. From November 2017 to November 2019, 87 patients with interstitial nephritis treated in our hospital were enrolled and divided into an acute group (n=42) and a chronic group (n=45) based on pathological results of renal biopsies. Forty healthy individuals after physical examination during the same period were enrolled into the reference group. Serum IL-6 levels were determined using the enzyme-linked immunosorbent assay (ELISA). RESULTS: Among the three groups, patients in the acute group showed the highest IL-6 level (P<0.001). The acute group obtained higher serum advanced oxidation protein products (AOPP) levels and glomerular filtration rate (GFR) than the other two groups (P<0.05). The acute group showed lower levels of CD34+ [number of positive microvessels (MVs)/HP], a smaller type III collagen positive area, and a larger type IV collagen positive area than the chronic group (P<0.05). The acute group obtained higher levels of IL-27 and tumor necrosis factor-α (TNF-α) than the chronic group (P<0.001). The acute group had higher levels of serum creatinine (SCr), erythrocyte sedimentation rate (ESR), estimated glomerular filtration rate (eGFR), and 24-hour urine protein quantity (24 h UPQ) than the other groups (P<0.001). The combined detection of serum IL-6, TNF-α, and micro-albumin (mALB) outperformed the stand-alone approach (P<0.05). Serum IL-32 and kidney injury molecule-1 (KIM-1) levels in the acute and chronic group were positively correlated with SCr and 24 h UPQ (P<0.05). CONCLUSIONS: Serum IL-6 shows a great potential as an important marker of disease progression in interstitial nephritis.