No abstract

The fine structure and immunoprotein content of the crystalloids are described in two cases of paraproteinemic crystalloidal keretopathy, both of which had clinical features thought by the referring ophthalmologists to be those of atypical lattice-type corneal dystrophy (presumably because of lattice-like lines). Most keratocytes in one case were surrounded by a mantle of densely packed tubular crystalloids. Individual tubules were annular in cross section with mean dimensions as follows: overall diameter, 29.32 nm (SD 1.26); internal diameter (core), 8.53 nm (SD 1.12); wall thickness, 10.39 nm (SD 0.85) (n = 10). Crystalloids were extracellular and found only in the corneal stroma, with none in Bowman's layer or Descemet's membrane. In the second case, the tubules had a similar distribution but formed geometric arrays with no clear relationship to, or envelopment of the keratocytes. The tubules were thin-walled, with mean dimensions as follows: overall diameter, 26.12 nm (SD 1.12); internal diameter (core), 15.46 nm (SD 1.12); wall thickness, 5.33 nm (SD 0) (n = 10). In both cases the tubules were kappa-light chain- and gamma-chain-positive. Laboratory investigations revealed the presence of two IgM-kappa paraproteins and an IgG-kappa paraprotein in the serum of the first patient. The second patient had an IgG-kappa paraproteinemia and bone marrow changes consistent with low-grade non-Hodgkin's lymphoma. These cases emphasize and extend the morphological range of corneal IgG crystalloids; the second case also demonstrates that corneal IgG crystalloids may be an early indicator of un underlying immunoproliferative disease.

The ultrastructural appearances of corneal crystalloidal deposits are described in two patients with an IgG-kappa paraproteinemia of uncertain pathogenesis. The crystalloids in one patient were overwhelmingly intracellular and were found mainly in stromal keratocytes, but also in basal corneal epithelial cells and the limbal vascular endothelium. Four types of crystalloid or immunoprotein-containing granules were recognizable in this case: 1) fibrillary crystalloids with a curvilinear filamentous substructure; 2) angulated geometric crystalloids that often had a linear filamentous substructure and transverse or oblique periodicity; 3) cordlike crystalloids; and 4) lysosomelike granules with amorphous contents. Immunoelectron microscopy demonstrated that all of these structures labeled for kappa-light chains, and rectangular type 2 crystalloids showed approximately a twofold greater concentration of the colloidal gold probe than the type 1 fibrillary crystalloids. The evidence suggested development of the crystalloids within lysosomes, with a progression from the granules containing amorphous material, through fibrillary crystalloids, to the geometric structures. The circumferential distribution of the corneal deposits, as well as the presence of vascular endothelial crystalloids and reduplication of external laminae around limbal blood vessels, suggests that the crystalloids originated predominantly or entirely from the blood, with transport of immunoprotein across damaged limbal microvasculature. The abnormal vasculature may also have contributed to corneal edema, which in turn may have exacerbated corneal opacification. The crystalloidal deposits in the other case were exclusively extracellular; they were located beneath and between corneal basal epithelial cells, and predominantly as a mantle around individual keratocytes. The crystalloids in this case consisted overwhelmingly of thick-walled tubules about 40 nm in diameter that labeled for both kappa-light chains and gamma chains with the colloidal gold immunoprobe. In addition, lucent vesicles within keratocytes were found only in sections labeled for kappa-light chains and were positive. The factors that might contribute to the formation of corneal crystalloidal deposits in immunoproliferative disorders are discussed, and include: 1) an inherent propensity for crystallization of some immunoglobulins or kappa-light chains, perhaps because of abnormal molecular structure; and 2) local factors in the cornea that might promote deposition and crystallization of immunoprotein, such as temperature, pH, the water content, and extracellular matrix components.

Subcutaneous injection of sterile air in rodents results in the formation of an air pouch with a lining morphologically similar to synovium (Edwards et al., 1981). We extended the comparison between pouch and synovial tissue and confirmed broad similarities in structure and function but also noted important differences. The air pouch was used to study the time course of the acute inflammatory response to heat aggregated human IgG. Saline washout of the pouch allowed simultaneous measurement of cellular and mediator components of the inflammatory exudate. The aggregates were rapidly phagocytosed by the pouch lining cells, resulting in acute inflammation characterised by polymorphonuclear leucocyte infiltration with peak numbers in the exudate at 12 hours, temporally dissociated from the earlier peak of PGE2 at 3 hours.