RESUMEN
Background: Patients with systemic lupus erythematosus (SLE), an autoimmune disease, have a higher risk of cardiovascular (CV) disease and death. In addition, up to 40%-50% of SLE patients develop lupus nephritis (LN) and chronic kidney disease, which is an additional CV risk factor. Thus, the individual contributions of LN and other SLE-specific factors to CV events are unclear. Methods: In this study, we investigated the effect of LN on the development of CV changes using the female NZBxNZW F1 (NZB/W) mouse model of lupus-like disease, with female NZW mice as controls. Standard serologic, morphologic, immunohistologic, and molecular analyses were performed. In a separate group of NZB/W mice, systolic blood pressure (BP) was measured during the course of the disease using tail plethysmography. Results: Our data show marked CV changes in NZB/W mice, i.e., increased heart weight, hypertrophy of the left ventricle (LV) and septum, and increased wall thickness of the intramyocardial arteries and the aorta, which correlated with the progression of renal damage, but not with the age of the mice. In addition, systolic BP was increased in NZB/W mice only when kidney damage progressed and proteinuria was present. Pathway analysis based on gene expression data revealed a significant upregulation of the response to interferon beta in NZB/W mice with moderate kidney injury compared with NZB mice. Furthermore, IFI202b and IL-6 mRNA expression is correlated with CV changes. Multiple linear regression analysis demonstrated serum urea as a surrogate marker of kidney function and IFI202b expression as an independent predictor for LV wall thickness. In addition, deposition of complement factors CFD and C3c in hearts from NZB/W mice was seen, which correlated with the severity of kidney disease. Conclusions: Thus, we postulate that the pathogenesis of CV disease in SLE is affected by renal impairment, i.e., LN, but it can also be partly influenced by lupus-specific cardiac expression of pro-inflammatory factors and complement deposition.
RESUMEN
The differential diagnosis of T cell-mediated rejection (TCMR) and BK-virus nephropathy (BKVN) in renal transplant biopsies is notoriously difficult. Therefore, attempts were made to differentiate between the two by characterizing the immune cell infiltrate. Using immunohistochemistry, the distribution of immune cell (sub)populations such as CD4(+) T helper (TH), TH1, TH2, CD8(+) cytotoxic T cells, regulatory T cells, B cells, plasma cells and follicular dendritic cells was determined in a total of 38 renal biopsy specimens. In addition, the expression of the HLA class I antigen presentation machinery (APM) components was investigated. In general, the frequency of T cells was higher than B cells, and TH cells outnumbered cytotoxic T cells with a predominance of TH2 over TH1 cells. In BKVN, a significantly higher number of plasma cells was observed (P = .028), and interstitial fibrosis and tubular atrophy was more pronounced in BKVN (P = .007) compared to TCMR. The expression of components of the HLA class I APM was not affected by the infection with BK virus compared to TCMR. These findings indicate a TH2 shift in renal transplants in the context of alloreactive and virus-induced inflammation maybe as a consequence of immunosuppression, which usually targets T cell reaction. The predominance of plasma cells might underline an important role of humoral immunity in BKVN. Moreover, BK virus does not seem to modulate the expression of HLA class I APM as a strategy of immune evasion.
