[Secondary glomerulonephritis in neurofibromatosis type 1. Two case reports]. / Síndrome nefrótico secundario en neurofibromatosis tipo 1. A propósito de dos casos.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant neurocutaneous disorder with systemic clinical manifestations. There are few publications about the renal effects of this disease, with renal vascular disease and adrenal tumors being the most frequent forms of renal involvement, while cases describing glomerular effects are exceptional. Despite the lack of published information, common molecular mechanisms in both NF-1 and nephrotic syndrome, involving the mTOR pathway, were suggested to explain a possible association between both pathologies. We present two cases of renal involvement in the form of nephrotic syndrome in patients diagnosed with NF1. A 41-year-old female was diagnosed of NF-1 in the context of a nephrotic syndrome with resistance to steroid treatment; the renal biopsy revealed a diagnosis of minimal changes disease. The second case is other 71-year-old woman with a history of NF-1, who presented a nephrotic syndrome and secondary renal amyloidosis.

Autoantibodies reactive with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy.

Autoantibodies reacting with extracellular matrix proteins have been extensively studied in various autoimmune connective tissue diseases. Because of the possibility that such antibodies may play a role in orbital connective tissue inflammation in thyroid-associated ophthalmopathy (TAO), we studied the humoral immune response against specific extracellular matrix (ECM) proteins, namely: collagen types I, III, IV, V (CI, CIII, CIV, CV), fibronectin (FN), and laminin (LM). Anti-ECM antibodies of immunoglobulin G (IgG), IgA, and IgM classes were determined by enzyme linked immunosorbent assay (ELISA). Overall, sera from 50% of patients with TAO contained antibodies reactive against one or more ECM proteins, compared to 27% with Graves' disease (GD) without evident eye involvement, 28% with Hashimoto's thyroiditis (HT), and 9% of normal subjects. Serum anti-CI, anti-CIII, anti-CV and anti-LM levels were significantly (p<0.05) higher in patients with TAO than in normals. Anti-CI, anti-CV and anti-LM reactivity was antigen-specific in most TAO sera, while anti-CIII antibodies cross-reacted with other antigens. Anti-collagen antibodies were mainly of the IgG class. To determine the structural epitopes of these proteins, we performed immunoblotting studies on cyanogenbromide (CNBr)-derived peptides of CI and CV. While sera from 9 of 10 patients with TAO reacted with CI peptides, the response was polyclonal and uniform in all patients. However, only 2 of 10 TAO sera reacted with CV peptides. In conclusion, our study suggests that a variety of ECM proteins (CI, CV, LM) may be secondary autoantigens that are recognized by antibodies in TAO. While these antibodies appear to react with epitopes expressed on both native and denatured proteins, and may therefore have the potential to bind to ECM in vivo, their pathogenic role in TAO remains unknown.

T cell interactions with extracellular matrix proteins in patients with thyroid-associated ophthalmopathy.

Although thyroid-associated ophthalmopathy (TAO) is now generally accepted as an autoimmune inflammatory disorder of the extraocular muscles and the orbital connective tissue, its aetiopathogenesis remains poorly understood. Recent data indicate that impaired interactions between T cells and extracellular matrix (ECM) proteins may play an important role in development and maintaining of an inflammatory process. We report here results of the study focusing on interactions between T lymphocytes and collagen-I (Coll-I), collagen-IV (Coll-IV), fibronectin (FN), laminin (LM) in patients with TAO. Using a standard peripheral blood mononuclear cells (PBMC) proliferation assay, we observed a markedly enhanced T cell response to Coll-I in patients with active TAO (mean SI=4.5). The proliferatory response to Coll-I was significantly greater (Wilcoxon test; p < 0.001) than in normal subjects (mean SI=1.88), patients with stable TAO (mean SI=2.05) and patients with thyroid autoimmune diseases (AITD) without ophthalmopathy (mean SI=2.49). PBMC stimulation by Coll-I is likely to be antigen-dependent requiring engagement of the T cell receptor with collagen peptides, rather than mediated via integrins. The percentage of circulating CD29+ (beta1 integrin chain) T cells was not increased in patients with active TAO. Additionally in the assay of costimulation of CD3-mediated proliferation, we found that peripheral blood T cells from patients with TAO and AITD were costimulated only by FN. On the other hand a markedly enhanced costimulation of CD3-mediated proliferative responses by Coll-I, Coll-IV, FN and LM were observed in a retrobulbar T cell line. We conclude that abnormalities in T cell interactions with ECM proteins, especially Coll-I may play a role in the pathogenesis of TAO.

[Pharmacologic effect of excess iodine on type I thyroxine 5'-deiodinase activity in rat thyroid]. / Wplyw farmakologicznych dawek jodu na aktywnosc enzymu tyroksyna-5'-dejodynazy typu I w gruczole tarczowym szczurów.

Many mechanism may participate in the inhibition of thyroid function by excess of iodine. The present study was aimed at answering the question, whether the excess of iodine influences the activity of type I thyroxine 5'-deiodinase. To 40 female rats fed with standard diet a dose of 42 micrograms of iodine daily was administered into the stomach through the gastric tube. Control group consisting of 10 rats received standard diet only. Part of the animals was sacrificed after each of the consecutive time intervals (2, 4, 7 and 14 days of treatment with iodine) and the activity of deiodinase in the thyroid as well as the blood serum levels of hormones, T3 and T4, were determined. A decrease in the activity of deiodinase in comparison with control group was observed during the whole experiment, the highest inhibition occurring after 4 days of treatment with iodine. A fall in the concentration of T3 was observed after the second and fourth dose of iodine, with no change in T4 concentration. The results of the experiments indicate that the excess of iodine inhibits the activity of type I thyroxine 5'-deiodinase in the thyroid.