Growth-promoting effect of Rh(D) antibody on human pancreatic islet cells.
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.


METHODS
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 microg/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.
Department of Newborn Care, Royal Hospital for Women, Randwick NSW 2031, Sydney, Australia. johnfeller@bigpond.com
John M
JM
Feller
Ann M
AM
Simpson
Margaret
M
Nelson
M Anne
MA
Swan
Philip J
PJ
O'Connell
Wayne J
WJ
Hawthorne
Chang
C
Tao
Bronwyn A
BA
O'Brien
D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005312:Fetal Blood / Q000276:immunology; D006801:Humans; D007231:Infant, Newborn; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D007518:Isoantibodies / Q000494:pharmacology*; D012204:Rh-Hr Blood-Group System / Q000378:metabolism; D018029:Rho(D) Immune Globulin
D007328:Insulin; D007518:Isoantibodies; C061961:RHO(D) antibody; D012204:Rh-Hr Blood-Group System; D018029:Rho(D) Immune Globulin; C026410:Rho(D) antigen