Am J Perinatol 2011; 28(6): 461-466
DOI: 10.1055/s-0030-1270113
© Thieme Medical Publishers

Intravenous Immunoglobulins for Neonatal Alloimmune Neutropenia Refractory to Recombinant Human Granulocyte Colony-Stimulating Factor

Aurélie Desenfants1 , Eric Jeziorski2 , Odile Plan1 , Michel Rodière2 , Marie Rimbert3 , Jean Yves Muller3 , Jacques Taïb4 , Gilles Cambonie1
  • 1Centre Hospitalier Régional Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Service de Pédiatrie Néonatale, Montpellier
  • 2Centre Hospitalier Régional Universitaire de Montpellier, Hôpital Arnaud de Villeneuve, Service de Pédiatrie Générale, Montpellier
  • 3Centre Hospitalier Régional Universitaire de Nantes, Institut de Biologie et Immunologie, Nantes
  • 4Centre Hospitalier Régional Universitaire de Montpellier, Hôpital Saint-Eloi, Laboratoire d'Hématologie, Montpellier, France
Further Information

Publication History

Publication Date:
06 December 2010 (online)

ABSTRACT

Neonatal alloimmune neutropenia (NAN) results from neutrophil destruction by transplacental maternal neutrophil-specific immunoglobulin G (IgG) antibodies directed against the antigen inherited from the father. Treatment is usually based on recombinant human granulocyte colony-stimulating factor (G-CSF) and prevention or treatment of infection. We report the case of neutropenia in a newborn discovered because of fetomaternal infection. The bone marrow biopsy showed normal cellularity. Granulocyte typing, granulocyte cross-matching, and serum assays showed anti-neutrophil antibodies specific for human neutrophil antigen-1c, an antigen rarely involved in this disease. This NAN was refractory to G-CSF but responded to intravenous immunoglobulin (IVIG). IVIG should be considered as a second-line treatment in NAN refractory to G-CSF. Clinical trials, however, are required to define the optimal management of NAN, a rare but probably underestimated life-threatening situation for newborns.

REFERENCES

  • 1 Berliner N, Horwitz M, Loughran Jr T P. Congenital and acquired neutropenia.  Hematology (Am Soc Hematol Educ Program). 2004;  63-79
  • 2 Bux J, Jung K D, Kauth T, Mueller-Eckhardt C. Serological and clinical aspects of granulocyte antibodies leading to alloimmune neonatal neutropenia.  Transfus Med. 1992;  2 143-149
  • 3 Williams B A, Fung Y L. Alloimmune neonatal neutropenia: can we afford the consequences of a missed diagnosis?.  J Paediatr Child Health. 2006;  42 59-61
  • 4 Tomicic M, Starcevic M, Zach V, Hundric-Haspl Z. Alloimmune neonatal neutropenia due to anti-HNA-2a alloimmunization with severe and prolonged neutropenia but mild clinical course: two case reports.  Arch Med Res. 2007;  38 792-796
  • 5 Verheugt F W, von dem Borne A E, Décary F, Engelfriet C P. The detection of granulocyte alloantibodies with an indirect immunofluorescence test.  Br J Haematol. 1978;  38 151
  • 6 Jiang A F, Lalezari P. A micro-technique for detection of leukocyte agglutinins.  J Immunol Methods. 1975;  7 103-108
  • 7 Bux J, Kober B, Kiefel V, Mueller-Eckhardt C. Analysis of granulocyte-reactive antibodies using an immunoassay based upon monoclonal-antibody-specific immobilization of granulocyte antigens.  Transfus Med. 1993;  3 157-162
  • 8 Fasth A. Immunoglobulin for neonatal agranulocytosis.  Arch Dis Child. 1986;  61 86-87
  • 9 Minchinton R M, McGrath K M. Alloimmune neonatal neutropenia—a neglected diagnosis?.  Med J Aust. 1987;  147 139-141
  • 10 Gilmore M M, Stroncek D F, Korones D N. Treatment of alloimmune neonatal neutropenia with granulocyte colony-stimulating factor.  J Pediatr. 1994;  125 (6 Pt 1) 948-951
  • 11 Rodwell R L, Gray P H, Taylor K M, Minchinton R. Granulocyte colony stimulating factor treatment for alloimmune neonatal neutropenia.  Arch Dis Child Fetal Neonatal Ed. 1996;  75 F57-F58
  • 12 Bédu A, Rohrlich P, Farnoux C et al.. [Neonatal alloimmune neutropenias. Importance of treatment with granulocyte colony-stimulating factor (G-CSF). Report of 2 new cases].  Arch Pediatr. 1999;  6 1297-1301
  • 13 Kerst J M, de Haas M, van der Schoot C E et al.. Recombinant granulocyte colony-stimulating factor administration to healthy volunteers: induction of immunophenotypically and functionally altered neutrophils via an effect on myeloid progenitor cells.  Blood. 1993;  82 3265-3272
  • 14 Stroncek D F, Shankar R, Litz C, Clement L. The expression of the NB1 antigen on myeloid precursors and neutrophils from children and umbilical cords.  Transfus Med. 1998;  8 119-123
  • 15 Bedu A, Baumann C, Rohrlich P, Duval M, Fenneteau O, Cartron J. Failure of granulocyte colony-stimulating factor in alloimmune neonatal neutropenia.  J Pediatr. 1995;  127 508-509
  • 16 Maheshwari A, Christensen R D, Calhoun D A. Resistance to recombinant human granulocyte colony-stimulating factor in neonatal alloimmune neutropenia associated with anti-human neutrophil antigen-2a (NB1) antibodies.  Pediatrics. 2002;  109 e64
  • 17 Bux J. International Society of Blood Transfusion . Nomenclature of granulocyte alloantigens. ISBT Working Party on Platelet and Granulocyte Serology, Granulocyte Antigen Working Party.  Transfusion. 1999;  39 662-663
  • 18 Bux J, Stein E L, Bierling P et al.. Characterization of a new alloantigen (SH) on the human neutrophil Fc gamma receptor IIIb.  Blood. 1997;  89 1027-1034
  • 19 Hessner M J, Shivaram S M, Dinauer D M, Curtis B R, Endean D J, Aster R H. Neutrophil antigen (FcgammaRIIIB) SH gene frequencies in six racial groups.  Blood. 1999;  93 1115-1116
  • 20 Curtis B R, Reno C, Aster R H. Neonatal alloimmune neutropenia attributed to maternal immunoglobulin G antibodies against the neutrophil alloantigen HNA-1c (SH): a report of five cases.  Transfusion. 2005;  45 1308-1313
  • 21 Latini G, Del Vecchio A, Rosati E, Borzini P, Chirico G, Rondini G. Different responses to granulocyte colony-stimulating factor treatment in siblings with alloimmune neonatal neutropenia.  Acta Paediatr. 1999;  88 1407-1409
  • 22 Cairo M S. Cytokines: a new immunotherapy.  Clin Perinatol. 1991;  18 343-359
  • 23 Larroche C, Chanseaud Y, Garcia de la Pena-Lefebvre P, Mouthon L. Mechanisms of intravenous immunoglobulin action in the treatment of autoimmune disorders.  BioDrugs. 2002;  16 47-55
  • 24 Boros P, Gondolesi G, Bromberg J S. High dose intravenous immunoglobulin treatment: mechanisms of action.  Liver Transpl. 2005;  11 1469-1480
  • 25 Galeotti C, Maddur M S, Kazatchkine M D, Mouthon L, Kaveri S V. [Intravenous immunoglobulins in autoimmune and inflammatory disorders: beyond a simple substitution].  Transfus Clin Biol. 2009;  16 75-79
  • 26 Cartron J, Tchernia G, Celton J L et al.. Alloimmune neonatal neutropenia.  Am J Pediatr Hematol Oncol. 1991;  13 21-25
  • 27 Navarro M, Negre S, Matoses M L, Golombek S G, Vento M. Necrotizing enterocolitis following the use of intravenous immunoglobulin for haemolytic disease of the newborn.  Acta Paediatr. 2009;  98 1214-1217
  • 28 Figueras-Aloy J, Rodríguez-Miguélez J M, Iriondo-Sanz M, Salvia-Roiges M D, Botet-Mussons F, Carbonell-Estrany X. Intravenous immunoglobulin and necrotizing enterocolitis in newborns with hemolytic disease.  Pediatrics. 2010;  125 139-144

Gilles CambonieM.D. Ph.D. 

Neonatology, University Hospital Center of Montpellier, Arnaud de Villeneuve Hospital

371 Avenue du Doyen G. Giraud, 34295 Montpellier Cedex 5, France

Email: g-cambonie@chu-montpellier.fr

    >