Spontaneous nephrotic mice (ICGN mice), a new mutant strain of mouse from outbred ICR, were clinically, macroscopically, histologically and immunohistochemically studied to establish their value as a model for human nephrotic syndrome. Most of the affected mice developed proteinuria, hypoproteinaemia and hypercholesterolaemia, and some of them developed systemic oedema. A high concentration of blood urea nitrogen (BUN) and a low haematocrit value were also observed. The kidneys of severe cases showed a decrease in size and had a yellowish granular surface. These findings indicated that the mice were terminally affected by chronic renal insufficiency. Histopathology demonstrated glomerular lesions consisting of thickened basement membranes of the capillary loops with irregular spike-like protrusions and enlargement of the mesangium unaccompanied by cellular proliferation. The immunofluorescence technique revealed positive granular staining for IgA, IgG and IgM and to a lesser extent for C3 along the capillary loops in affected mice. The similarity between this spontaneous disease and human nephrotic syndrome caused by idiopathic glomerular lesions is discussed. ICGN mice may be a useful animal model for this human disease.

No abstract

Glomerular lesions in hereditary nephrotic mice (ICGN strain) were investigated by electron microscopy. The glomeruli of unaffected animals, which appeared normal by light microscopy, had developed an ultrastructural change in the glomerular capillary basement membrane (GCBM). There was a partial thickening of the GCBM with bilaminar splitting of the lamina densa and an electron-dense fibrillar material exhibiting cross-striations. In affected animals, light microscopy revealed a marked thickening of GCBM and an increase of mesangial matrix without cellular proliferation. By electron microscopy, multilaminar splitting of the lamina densa in the thickened GCBMs and fusion of the epithelial foot processes were observed. In some severely affected animals, immune complex deposition was found in GCBM, but little if any was observed in other animals. In the end, the glomeruli were globally sclerosed. Our findings suggest that initial structural abnormalities in GCBM may play an important role in the onset and development of the disease, though subsequent events such as immune complex deposition would modify the disease.

No abstract

Performances of anti-nuclear antibody testing by immunofluorescence assay (ANA-IFA) and enzyme immunoassay (ANA-EIA) were compared in relation to patient diagnosis. A total of 467 patient serum samples were tested by ANA-IFA (Kallestad; Sanofi) and ANA-EIA (RADIAS; Bio-Rad), and their age, sex, diagnosis, disease status, and medications were obtained through chart review. Reference ranges were established by testing 98 healthy blood donor samples. Eighty-six samples came from patients with diffuse connective tissue diseases, including systemic lupus erythematosus, discoid lupus erythematosus, or drug-induced lupus (n ‫؍‬ 71); systemic sclerosis, CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal motility abnormalities, sclerodactyly, and telangiectasia), or Raynaud's syndrome (n ‫؍‬ 8); Sjögren's syndrome (n ‫؍‬ 5); mixed connective tissue disease (n ‫؍‬ 5); and polymyositis or dermatomyositis (n ‫؍‬ 3). The sensitivity, specificity, positive predictive value, and negative predictive value for ANA-IFA were 87.2, 48.0, 29.1, and 93.9%, respectively, for the reference range of <1:160. For ANA-EIA, they were 90.7, 60.2, 35.8, and 96.4%, respectively, for the reference range of <0.9. ANA-EIA offers equivalent sensitivity and higher specificity compared to ANA-IFA. Anti-nuclear antibody (ANA) testing is widely used as a screening test in connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE), scleroderma, CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal motility abnormalities, sclerodactyly, and telangiectasia), Sjögren's syndrome, mixed connective tissue disease (MCTD), polymyositis, and dermatomyositis. However, positive ANA results are seen in a significant proportion of the elderly population (6, 17, 18, 20) and sensitivity of ANA testing varies widely from one clinical disease to another. For example, ANA testing has been reported to be positive in Ͼ95% of patients with SLE but in only 10 to 50% of patients with dermatomyositis and polymyositis (20). The first description of ANA was made by Hargraves and colleagues in 1948 when they observed LE (lupus erythematosus) cells in the bone marrow of patients with SLE (4). Currently, the most commonly used method for ANA testing is ANA-immunofluorescence assay (ANA-IFA) in which slides prepared from human epithelioid cells (HEp-2 cells) as a substrate are incubated with diluted serum. The presence of autoantibodies is detected by fluorescent antiimmunoglobulin antibody, and characteristic morphologic patterns of fluorescent staining are observed. Certain ANA-IFA patterns are associated with the presence of autoantibodies to certain nuclear antigens which in turn are associated with certain clinical states (7, 13, 17, 20). For example, a diffuse or homogenous pattern is associated with such clinical states as SLE, rheumatoid arthritis, scleroderma, Sjögren's syndrome, and drug-induced lupus. The ANA-IFA is a subjective assay requiring skilled personnel and is a manual assay with a significant amount of hands-on time. Therefore, ...