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Role of gamma globulins in pathogenesis of renal lesions in systemic lupus erythematosus and chronic membranous glomerulonephritis, with an observation on the lupus erythematosus cell reaction.

Utilizing the fluorescent antibody method for the histologic demonstration of localized gamma-globulins, we have made the following observations (in contradistinction to the lack of such findings in a variety of normal and pathologic, control kidneys). In systemic lupus erythematosus (a) gamma-globulins were localized in the thickened capillary walls, the "wire-loop" lesions, and the so called "hyaline thrombi" in glomeruli; (b) these sites of localization of gamma-globulins were correlated to a considerable degree with the pattern of accentuated eosinophilia of the glomeruli, as seen in hematoxylin-eosin sections, or with the pattern of PAS-positive areas in the glomeruli in sections stained with the periodic acid-Schiff reaction; (c) and gamma-globulins were localized rarely in large cytoplasmic granules in tubular epithelium and occasionally in glomerular capsular crescents, tubular protein casts, and inflammatory cells, particularly in the cytoplasm of cells identified as immature and mature plasma cells. In nephrotic glomerulonephritis (a) gamma-globulins were localized in the glomerular basement membrane and appertaining structures in chronic membranous glomerulonephritis; (b) gamma-globulins were apparently localized in the altered mesangium in chronic lobular glomerulonephritis; and (c) in the tubular protein casts, presumably representing abnormal glomerular filtrates, gamma-globulins were present in a lesser concentration and other serum proteins in a greater concentration than found in the glomeruli. In positive lupus erythematosus preparations the nuclei of leukocytes, while undergoing transformation and subsequent phagocytosis to form lupus erythematosus cells, were the sites of localization of gamma-globulin (presumably the lupus erythematosus factor) whereas in control preparations no nuclear localization of gamma-globulin occurred. These observations are discussed in relation to the pathogenesis of renal lesions in systemic lupus erythematosus, chronic membranous glomerulonephritis, and amyloidosis.

Amyloidosis↗

An electron microscope study of the glomerulus in nephrosis, glomerulonephritis, and lupus erythematosus.

Renal biopsies from 16 patients with nephrosis, 7 patients with glomerulonephritis, and 3 patients with disseminated lupus erythematosus were studied with the electron microscope. The observations presented indicate that early in the course of each of these diseases alterations occur in the fine structure of the glomeruli which serve to distinguish one disease process from another. In nephrosis, some distortion of the organization of the epithelial foot processes was seen in all patients. These epithelial changes constituted the early, consistent lesion of the disease. There was frequently also a swelling of the endothelium. In glomerulonephritis, pronounced proliferative changes involving the endothelium and to a lesser extent the epithelium, together with the laying down of a basement membrane-like material, represented the predominate pathologic processes. There was also a swelling of both endothelial and epithelial cytoplasm. The epithelial foot processes generally appeared normal. In patients with a clinically "mixed" picture of nephrosis and nephritis, the glomerular changes were likewise "mixed," for various combinations of epithelial, endothelial, and basement membrane abnormalities were present. In disseminated lupus erythematosus, a more or less generalized thickening of the basement membrane proper associated with a variable degree of endothelial proliferation was seen. It is suggested that an accentuation of the process of basement membrane thickening results in the "wire loop" appearance sometimes seen by light microscopy. Although the earliest alterations in glomerular fine structure were characteristic for each of the disease processes, at later stages the changes were not always distinctive. The resulting scarred or "hyalinized" glomeruli, composed of relatively homogeneous, basement membrane-like material, and a few atrophic cells, appeared quite similar. Although the functional implications of the structural changes observed remain obscure at this time, it is believed that insight into mechanisms may stem from such observations.

Basement Membrane↗

An unusual spleen.

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Glomerulonephritis↗

Glomerulonephritis.

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Glomerulonephritis↗