RESUMO
Thrombospondin type I domain-containing 7A (THSD7A), is a specific autoantigen of adult idiopathic membranous nephropathy (IMN), whose circulating antibody (THSD7A-AB) represents a promising biomarker for diagnosis of IMN. The objective of this meta-analysis is to investigate the diagnostic efficiency of THSD7A-AB for IMN. After rigorous data extraction, quality assessment, and data analysis, 10 articles (4545 patients) are included. For IMN, the summary sensitivity is 4% (2-7%), and the specificity is 99% (98-100%). The summary positive likelihood ratio (PLR) and negative likelihood ratio (NLR) are 5.40 (2.40-11.90) and 0.97 (0.95-0.99), respectively. The diagnostic odds ratio (DOR) is 6.00 (2.00-12.00). The area under the summary receiver operating characteristic curve (AUC) is 0.78 (0.74-0.81). For M-type phospholipase A2 receptor (PLA2R)-negative IMN, the summary sensitivity is 8% (6-10%), specificity is 100% (99-100%). The summary PLR and NLR are 15.80 (5.70-44.00) and 0.93 (0.91-0.95), respectively. The DOR is 17.00 (6.00-48.00). The AUC is 0.99 (0.98-1.00). THSD7A-AB has higher diagnostic value in PLA2R-negative patients than in IMN patients. These results suggest that THSD7A-AB could possibly be applied as an auxiliary non-invasive diagnostic method for PLA2R-negative IMN.
RESUMO
IQGAP1 is a multifunctional, 190-kDa scaffolding protein that plays an important role in the regulation of cell adhesion, migration, proliferation, differentiation, polarization and cytoskeletal remodeling. IQGAP1 is ubiquitously expressed in human organs and is highly expressed in the kidney. Currently, the site-specific expression of IQGAP1 in the human nephrons is unclear. We performed Western blotting analysis, immunohistochemistry and double-immunolabeling confocal microscopic analysis of IQGAP1 with specific biomarkers of each nephron segment to study the expression and distribution of IQGAP1 in human nephrons. We found that IQGAP1 was strongly expressed in human podocytes and glomerular endothelial cells, but weakly expressed in glomerular mesangial cells. In human renal tubules, IQGAP1 was strongly expressed in the collecting duct, moderately expressed in the proximal tubule, medullary loop, distal convoluted tubule and connecting tubule. IQGAP1 staining was much stronger in the apical membrane in the proximal tubule, thick descending limb and thick ascending limb of medullary loop and collecting duct. However, the expression of IQGAP1 was mainly in the basolateral membrane of the connecting tubule, and diffusely in the thin limb of medullary loop and distal convoluted tubule. The interaction between IQGAP1 and F-actin suggested that cytoskeleton regulation may be the underlying mechanism mediating the effect of IQGAP1 in human nephrons. To the best of our knowledge, this is the first report of specific expression and differential subcellular location of IQGAP1 in human nephrons. The site-specific expression pattern of IQGAP1 suggests that IQGAP1 may play diverse roles in various human nephron segments.
