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Recently, plasma globotriaosylsphingosine (lyso-Gb3) has attracted attention as a biomarker of Fabry disease. However, we found a subset of Fabry disease patients who did not show any increase in the plasma lyso-Gb3 concentration, although other patients exhibited apparent enhancement of it. This subset predominantly exhibited the clinical phenotype of later-onset Fabry disease, and gene analysis revealed that the patients harbored the M296I mutation common to Japanese Fabry patients. This amino acid substitution is predicted to cause a small conformational change on the surface of the α-galactosidase A molecule, resulting in residual enzyme activity. Plasma lyso-Gb3 is a good biomarker of Fabry disease but care should be taken when it is used for a definitive diagnosis.

Background Depletion of glomerular podocytes is an important feature of progressive diabetic nephropathy. Although the most plausible explanation for this podocyte depletion is detachment from the glomerular basement membrane after cellular apoptosis, the mechanism is unclear. Fibroblast-specific protein 1 (FSP1; encoded by the S100A4 gene) is a member of the S100 family of calcium-binding proteins and is constitutively expressed in the cytoplasm of tissue fibroblasts or epithelial cells converted into fibroblasts by means of epithelial-mesenchymal transition. Study Design Retrospective cross-sectional analysis. Settings & Participants 109 patients with type 2 diabetes mellitus, of whom 43 (39%) underwent kidney biopsy. Predictor Clinical stage (4 categories) and histological grade (5 categories) of diabetic nephropathy. Outcome FSP1 expression in podocytes in urine and glomeruli in kidney biopsy specimens. Measurements Immunohistochemistry, real-time polymerase chain reaction, and in situ hybridization. Results 38 of 109 patients (35%) were normoalbuminuric, 16 (15%) had microalbuminuria, 8 (7%) had macroalbuminuria, and 47 (43%) had decreased kidney function. Approximately 95% of podocytes in urine sediment were not apoptotic, and 86% expressed FSP1. The number of FSP1-positive podocytes in urine sediment was significantly larger in patients with macroalbuminuria than in those with normoalbuminuria ( P = 0.03). Intraglomerular expression of FSP1 occurred almost exclusively in podocytes from patients with diabetes, and the number of FSP1-positive podocytes was larger in glomeruli showing diffuse mesangiopathy than in those showing focal mesangiopathy ( P = 0.01). The number also was larger in glomeruli with nodular lesions than in those without nodular lesions ( P Limitations Nonrepresentative study population. Conclusions These results suggest that the appearance of FSP1 in podocytes of patients with diabetes is associated with more severe clinical and pathological findings of diabetic nephropathy, perhaps because of induction of podocyte detachment through epithelial-mesenchymal transition–like phenomena.

Background Fractalkine (Fkn) is a chemokine that affects cells expressing its receptor, CX3CR1, including CD16-positive (CD16 + ) monocytes/macrophages (CD16 + Mos). The relationship of levels of glomerular Fkn expression and infiltration by CD16 + Mos with the severity and diversity of glomerular lesions in human lupus nephritis is not known. Study Design Retrospective cross-sectional analysis of variables observed in biopsy specimens. Settings & Participants 88 patients with systemic lupus erythematosus. Predictor Histological class and severity of lupus nephritis according to the International Society of Nephrology/Renal Pathology Society and clinicopathologic factors. Outcomes Outcome variables are assays related to the degree of glomerular Fkn expression and CD16 + Mo infiltration. Measurements Immunohistological grading of Fkn staining, number of CD16 + Mos, and messenger RNA levels of Fkn and CD16 in glomeruli. Results Patients with proliferative lupus nephritis (class III and IV glomeruli) showed significantly greater glomerular Fkn expression and CD16 + Mo counts than those with other classes. Infiltrating CD16 + Mos within glomeruli expressed CX3CR1. Moreover, glomerular Fkn expression significantly correlated with the histopathologic activity index and CD16 + Mo counts, and CD16 + Mo counts significantly correlated with serum levels of blood urea nitrogen, complement (CH 50 ), and anti-DNA antibody; estimated glomerular filtration rate; and urinary protein excretion. Glucocorticoid therapy had a tendency to decrease both glomerular Fkn expression and CD16 + Mo counts. Limitations Only frozen biopsy specimens (from 49 patients) were analyzed for the evaluation of glomerular Fkn expression. Conclusion Disease activity and proliferative glomerular lupus nephritis lesions are associated with the glomerular Fkn expression and CD16 + Mo accumulation.

We studied vascular endothelial growth factor (VEGF) mRNA synthesis by peripheral blood mononuclear cells (PBMCs) in 30 patients with acute myocardial infarction (AMI) and 20 healthy individuals. PBMCs were isolated from all patients on days 3 and 14 after the onset of aMI, and from all of control individuals. To prepare samples containing identical amounts of GAPDH cDNA, competitive PCR was performed by co-amplifying serial dilutions of GAPDH mutant templates. Next, to measure VEGF cDNA quantitatively in the samples containing identical amounts of GAPDH, we also used competitive PCR by co-amplifying mutant templates of VEGF. The serum VEGF concentrations on day 14 in patients with aMI were measured by an ELISA method. Higher levels of VEGF mRNA in PBMCs were present on day 14 than either on day 3 or in the control group. Serum VEGF concentrations correlated with the VEGF mRNA levels of PBMCs on day 14. Peak serum CK levels correlated well with VEGF mRNA levels of PBMCs on day 14. The present findings suggest that PBMCs may be one of the candidates responsible for elevated circulatory VEGF protein following aMI. In addition, VEGF mRNA may be overexpressed in PBMCs in response to cardiac muscle damage.