Antibodies against striated muscle, connective tissue and nuclear antigens in patients with thyroid-associated ophthalmopathy: should Graves' disease be considered a collagen disorder?

The identity and subcellular localization of the principal extraocular muscle (EOM) antigens and prevalences of the corresponding serum autoantibodies in thyroid-associated ophthalmopathy (TAO) need to be clarified. We have used porcine eye muscle tissue, which expresses all autoantigens identified in human tissue, as substrate in an indirect immunofluorescence assay. Several different patterns of antibody binding to EOM tissue antigens were observed with sera from patients with TAO namely, membrane, cytoplasmic, interstitial (endomysial) and nuclear.

Serum antibodies reactive with eye muscle antigens and the TSH receptor in a euthyroid subject who developed ophthalmopathy and Graves' hyperthyroidism.

Serum antibodies reactive with eye muscle autoantigens, in particular a 64-kDa protein that is also expressed in the thyroid, and the TSH receptor, are associated with the ophthalmopathy that occurs in about 50% of patients with Graves' hyperthyroidism. We have had the opportunity to study a euthyroid, apparently normal, 35-year-old woman with a family history of thyroid autoimmunity and "colitis" but no clinical or biochemical evidence for thyroid disease or ophthalmopathy, who developed Graves' hyperthyroidism and ophthalmopathy together 18 months later. Serum taken when the patient was first seen was positive for antibodies reactive with (i) 9 different eye muscle proteins ranging in size from 15 to 130 kDa, notably those of 64, 55, and 50 kDa, by immunoblotting with eye muscle membranes, (ii) eye muscle and Müller's muscle cell membrane antigens in antibody-dependent cell-mediated cytotoxicity (ADCC), (iii) an eye muscle cytoplasmic antigen in indirect immunofluorescence, and (iv) the TSH receptor as measured in a radioreceptor binding inhibition assay.

Should Graves' disease be considered a collagen disorder of the thyroid, skeletal muscle and connective tissue?

Graves' disease comprises hyperthyroidism, ophthalmopathy, pretibial myxedema and acropachy, which occur separately or in various combinations. We have used the indirect immunofluorescence test to investigate reactivity of sera from patients with autoimmune thyroid disorders with and without ophthalmopathy, with porcine extra ocular muscle (EOM) and control tissue substrates. Sera from 75% of patients with Graves' hyperthyroidism (GH) and ophthalmopathy, which we call thyroid-associated opthalmopathy (TAO), contained one or more antibodies reactive with EOM compared to 32% of those with GH without the eye disorder, 41% of patients with Hashimoto's thyroiditis (HT), and 16% of normals.

Ultrastructural immunohistochemical localization of polyclonal IgG, C3, and amyloid P component on the congo red-negative amyloid-like fibrils of fibrillary glomerulopathy.

Renal biopsies from seven patients with Congo red-negative amyloid-like fibrillary glomerulopathy (FGP) were examined by protein A gold immuno-electron microscopy. Ultrastructurally, the fibrils in all cases exhibited positive immunostaining for IgG, both Ig light chains, C3, and amyloid P component (AP), but did not show positive immunostaining for glomerular basement membrane (GBM)-associated proteins (collagen type IV and heparan-sulfate proteoglycans) or microfibril-associated proteins (fibronectin and fibrillin). In a triple-label study, AP and IgG were colocalized along the same fibril, whereas the gold probes for the detection of collagen type IV were absent.

Acute silicosis responding to corticosteroid therapy.

The course of acute silicosis usually is relentlessly progressive. Death results from cor pulmonale and respiratory failure, with mycobacterial infection a frequent serious complication. Attempts to treat the illness generally have been unavailing.

Persistence of scleroderma-like phenotype in normal fibroblasts after prolonged exposure to soluble mediators from mononuclear cells.

Supernatants of mononuclear cells (MNC-SN) were shown to increase synthesis of glycosaminoglycan (GAG) by cultured normal dermal fibroblasts. Fibroblasts from the skin of patients with progressive systemic sclerosis (PSS, scleroderma) were hyporesponsive. We exposed fibroblasts outgrowing from explants of normal adult skin to MNC-SN for up to 30 generations in culture.

Mononuclear-cell subsets in human idiopathic crescentic glomerulonephritis (ICGN): analysis in tissue sections with monoclonal antibodies.

Mononuclear inflammatory cells (MIC) were analyzed in renal biopsies from 16 patients with ICGN (7 with glomerular immune complex deposits, 3 with anti-GBM disease, and 6 without immune deposits) by the avidin-biotin-immunoperoxidase technique utilizing monoclonal antibodies to cell surface antigens: T11 (total T), T4 (inducer/helper T), T8 (suppressor/cytotoxic T), B1 (B cells), M1 (monocytes/granulocytes), and Leu 7 [natural killer (NK) cells]. Total MIC were significantly increased in both glomeruli and interstitial tissues of the patients. Interstitial MIC consisted mainly of lymphocytes (80%) and monocytes (19%), with small numbers of B and NK cells present.

Mononuclear cell subsets in human renal disease. Enumeration in tissue sections with monoclonal antibodies.

Mononuclear inflammatory cells (MIC) in renal biopsies from 37 patients with renal disease were studied by avidin--biotin--immunoperoxidase complex (ABC) technique, utilizing monoclonal antibodies to cell surface antigens: T11 (total T), T4 (inducer/helper), T8 (suppressor/cytotoxic), B1 (B cells), M1 (monocytes), and Leu-7 (natural killer, NK cells). Renal MIC consisted mostly of T cells and monocytes. T cells were a predominating cell type in the renal interstitium of all patients studied (64-88% of MIC).

Focal segmental glomerulosclerosis in Hodgkin's disease.

Development of Nil disease and focal segmental glomerulosclerosis (FGS) in sequential renal biopsies is reported in a patient with Hodgkin's lymphoma. Although steroid resistance was demonstrated, a complete and sustained clinical remission of the renal lesion followed anti-Hodgkin's chemotherapy. These findings support the hypothesis that Nil disease and FGS are manifestations of the same clinical entity.

T and B lymphocyte subsets in fenoprofen nephropathy.

Renal failure due to combined acute interstitial nephritis and minimal-change glomerulopathy is reported in two patients after fenoprofen therapy. In the interstitial infiltrates, T lymphocytes predominated over B lymphocytes in a ratio of four to one. The majority of B lymphocytes present were IgE-bearing cells.

Urinary immune complexes in patients with glomerular diseases. Their possible diagnostic implications.

Urine specimens from 65 patients with glomerular disease and from 62 controls were tested for the presence of immune complexes by agarose gel zone electrophoresis. Urinary immune complexes (UICs) were found in 18% of patients, correlating with the simultaneous occurrence of serum immune complexes and depending differentially on the histologic form of glomerular disorder. The UICs were found preponderantly in patients with severe crescentic glomerulonephritis, who had "gaps" in the glomerular basement membrane; in patients with epimembranous electron-dense deposits; and in patients with membrano-proliferative glomerulonephritis.

Talwin addict nephropathy.

Three patients with a 2-3 year history of parenteral abuse of pentazocine hydrochloride (Talwin) developed membranoproliferative glomerulonephritis type I. Clinical presentation included nephrotic syndrome, microscopic hematuria, and hypertension. Tissue studies disclosed 1+ to 4+ mesangial and subendothelial deposits of immunoglobulins (predominantly IgM) and complement components C1Q, C3 and C4 with focal reduplications of glomerular basement membranes.

IgA-containing circulating immune complexes in patients with igA nephropathy.

The role of circulating immune complexes in the pathogenesis of IgA nephropathy (Berger's disease) is controversial. Previous studies have shown that a minority of these patients have immune complexes, but the methods used have been able to detect only IgG- or IgM-containing circulating immune complexes. Using a sensitive specific Raji cell radioimmunoassay for IgA-containing circulating immune complexes, we have examined serum specimens from 12 patients with IgA nephropathy for the presence of IgA-containing circulating immune complexes.

Fenoprofen nephropathy: lipoid nephrosis and interstitial nephritis. A possible T-lymphocyte disorder.

Five patients are presented, each of whom had an acute idiosyncratic reaction to fenoprofen calcium (Nalfon) characterized by acute renal failure and marked proteinuria. Renal pathology was similar in all patients. Light microscopy revealed marked lymphocytic inflammatory infiltrates and normal glomeruli.

Circulating and deposited immune complexes in patients with glomerular disease: immunopathologic correlations.

The presence of circulating immune complexes (ICs), and alterations of serum immunoglobulins G, A, and M, properdin factor B, and C3 and C4 levels were correlated with glomerular immune deposits in 50 consecutive renal biopsy patients. Urine from 25 of these patients was also examined for ICs. Agarose gel zone electrophoresis (AGE) was used for IC screening.

Mechanisms of tissue injury in desquamative interstitial pneumonitis.

To evaluate a contribution of immunologic factors to the pathogenesis of desquamative interstitial pneumonitis (DIP), lung biopsy specimens from four patients were studied for immunoglobulin deposits in tissue and cellular characteristics by immunologic, ultrastructural and histochemical methods. Accumulations of large cells with vacuolated cytoplasm within the distal air spaces and marked increase in the numbers of type II pneumocytes lining pulmonary alveoli were observed in all cases. The cells in air spaces were identified as macrophages containing intracellular lysozyme and alpha-naphthyl acetate esterase.

Endodermal sinus tumor originating in the region of the pineal gland: ultrastructural and immunohistochemical study.

This is a case report of an endodermal sinus tumor (EST) arising in the pineal region of a 19-year-old girl (first case studied by electron microscopy). The ultrastructure of the tumor was similar to that of the previously reported cases of EST of ovaries, mediastinum, and sacrococcygeal area. A characteristic basement membrane-like material has been identified within endoplasmic reticulum of tumor cells and in intercellular spaces.