Growth-Promoting Effect of Rh(D) Antibody on Human Pancreatic Islet Cells

• Published in: The journal of clinical endocrinology and metabolism Vol. 93; no. 9; pp. 3560 - 3567
• Main Authors: Feller, John M., Simpson, Ann M., Nelson, Margaret, Swan, M. Anne, O'Connell, Philip J., Hawthorne, Wayne J., Tao, Chang, O'Brien, Bronwyn A.
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01-09-2008
• Subjects: Biological and medical sciences; Cell Proliferation - drug effects; Cell Survival - drug effects; Cells, Cultured; Endocrinopathies; Feeding. Feeding behavior; Female; Fetal Blood - immunology; Fundamental and applied biological sciences. Psychology; Humans; Infant, Newborn; Insulin - metabolism; Insulin Secretion; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; Islets of Langerhans - ultrastructure; Isoantibodies - pharmacology; Medical sciences; Rh-Hr Blood-Group System - metabolism; Rho(D) Immune Globulin; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Human; Obesity; Nutrition; Antibody; Growth; Nutrition disorder; Langerhans islet; Metabolic diseases; Rh-System; Cell; Endocrinology; Nutritional status; Endocrine pancreas
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-0510

Context/Objective: Hyperinsulinism with islet cell hyperplasia is a frequent complication, of unknown cause, in hemolytic disease of the newborn, occurring in Rh(D)-positive infants of Rh-isoimmunized Rh(D)-negative mothers, but not in infants with other hemolytic disorders. We investigated the possibility that trans-placentally acquired anti-D Ig is the cause of both conditions.
Design: Monolayer cultures of human islet cells were exposed to sera from Rh-isoimmunized mothers and newborns, where jaundice, hyperinsulinism, and hypoglycemia in the infant had ensued. Parallel cultures with anti-D, specific anti-D monoclonal antibodies, normal human Ig (15 μg/ml), and serum controls were also undertaken. Islet cell proliferation was determined by [3H]thymidine incorporation. Insulin storage and chronic and acute insulin secretion to glucose were analyzed by RIA. Rh(D) surface antigen expression was determined on islet cells by flow cytometric analysis.
Results: Islet cell proliferation and insulin secretion were significantly greater in coculture with test sera (P < 0.01; n = 8) and with anti-D (P < 0.001; n = 8), compared with either controls or Ig. After 8 d of growth, the static incubation experiment showed a 3.5-fold response to glucose stimulus in all sera. Rh(D) antigen expression was detected on the islet cell surface by flow cytometry, and islet cell morphology was normal. Colocalization of the proliferation marker Ki67 with insulin by immunofluorescent staining further indicated that Rh(D) antibody promoted islet growth.
Conclusions: The anti-Rh(D) islet cell proliferative effect generates neonatal hyperinsulinism in Rh isoimmunization. Anti-Rh(D) may have application for islet cell proliferation in diabetes mellitus treatment for Rh(D)-positive subjects. Further analysis is required.