Gail K. Naughton

The significance of vitiligo antibodies.

Little is known about the pathogenesis of vitiligo. It results from the destruction of melanocytes (1), but the cause of melanocyte destruction is not known (2-4). Immune mechanisms are suspected since vitiligo is frequently associated with a variety of organ specific antibodies and is 10-15 times more common in patients with autoimmune diseases (2-4). However, direct evidence for involvement of the immune system in the pathogenesis is sparse. No gross abnormalities have been found in nonspecific (5) or specific (6) parameters of cellular immunity. Bursectomy delays the ap.pearance of vitiligo in DAM chickens, suggesting antibodies may be involved in the pathogenesis (7). However, reports of antibodies to melanocytes in human vitiligo (8-10) have either not been confirmed by other investigators using the same technique (11) or result from other diseases concurrently afflicting the patients (12). Thus, complement-fixing antibodies to cytoplasmic antigens of melanocytes have been reported in a few patients with vitiligo and chronic mucocutaneous candidiasis (MCC) (9, 10, 13). However, a subsequent much larger study in 294 patients showed these to be associated with chronic MCC and not with vitiligo (12). This finding has been confirmed in another large study (14). Why patients with MCC develop antibodies to pigment cells cytoplasmic antigens is not clear. It may be related to the presence of shared antigens

Antibodies to surface antigens of pigmented cells in animals with vitiligo.

Abstract All of 24 animals (dogs, cats, and horses) with vitiligo were found to have antibodies to pigmented cells that could be detected by specific immunoprecipitation of radioiodinated, detergent-soluble surface macromolecules, and by indirect immunofluorescence on viable cells. These antibodies were not detected in 17 normal animals of the same species. The antibodies were directed to an 85-kDa surface antigen selectively expressed by pigmented cells that was not present on nonpigmented control cells. These observations suggest that vitiligo in animals is an autoimmune disease mediated to pigmented cells.

Evidence for an Erythropoietin-Stimulating Factor in Patients with Renal and Hepatic Disease

Recently, a factor was discovered in the serum of hepatectomized animals which was capable of augmenting the hepatic erythropoietin response to hypoxia when injected into normal rats. This substance was localized in the liver via an in situ perfusion technique and was termed the hepatic erythropoietic factor (HEF). Patients with kidney disease, liver disease, and combined renal and hepatic disease were studied in this report. Detectable HEF levels were found in the plasma of patients with both liver and kidney disease and were highest in anephric patients with various liver diseases. However, HEF levels were negligible in normal humans or in patients manifesting renal disease with no hepatic involvement. The data suggest that HEF-induced hepatic erythropoietin synthesis may occur in humans as well as in animals.

The Effects of Prostaglandins on Extrarenal Erythropoietin Production

Abstract The E and A series prostaglandins have been reported to stimulate erythropoiesis and renal erythropoietin (Ep) production. In the present study, these prostaglandins also stimulated the elaboration of extrarenal Ep in renoprival animals after hypoxia. This extrarenal response was primarily due to hepatic Ep synthesis; when subtotal hepatectomy (hepx) was followed by nephrectomy, the Ep response to hypoxia was almost completely abolished. The synthetic methylated prostaglandins (16, 16-dimethyl E2 and (15s)-15 methyl E2) exerted the most potent effects on both the hepatic and renal Ep response. It is believed that this is attributable, at least in part, to the greater stability of these compounds in vivo. Prostaglandins do not appear to be capable of substantially elevating Ep production by the regenerating liver. When compared to vehicle- or saline-injected rats, a greater stimulation of hepatic Ep elaboration after prostaglandin treatment was observed in animals with normal livers than in rats with liver regenerating 72 hr after hepx.

Multilineage Hematopoietic Expression in a Three-Dimensional Long Term Bone Marrow Culture System

The initial attempts to grow bone marrow cells in semi-solid or liquid medium promoted only the terminal differentiation of hematopoietic stem cells in the absence of self-renewal, with cultures becoming hematopoietically unproductive after 1–2 weeks of culture. Subsequent work in the murine system by Dexter and co-workers demonstrated that the sustained growth of hematopoietic cells in liquid culture was possible if these cells were plated onto a pre-established monolayer of bone marrow stromal cells3. These cells synthesize the matrix necessary to support hematopoiesis and contribute trophic/regulatory factors to the hematopoietic microenvironment. Inclusive of this group are fibroblasts, adipocytes reticular adventitial cells, macrophages, and endothelia4. The Dexter long-term bone marrow culture (LTBMC) system sustains the self renewal of murine pluripotential stem cells (CFU-S) although the lineage restricted progenitors become predominantly myeloid in character after the first several weeks of culture3,5. This system can be modulated to favor the growth of lymphoid cells6,7 or erythroid progenitors8, but single cultures do not produce substantial numbers of each hematologic cell type concurrently.