Research Article| Volume 1, ISSUE 2, P239-263, June 1981

Antibody-Mediated Perinatal Diseases

  • Moses S. Schanfield
    Immunohematology Laboratory, American Red Cross Blood Services, 4915 Auburn Avenue, Bethesda, Maryland 20014
    Adjunct Associate Professor, Genetics Program, George Washington University, Washington, D.C.

    Head, Immunohematology Laboratory, American Red Cross Blood Services, Bethesda, Maryland
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      The production of alloantibodies or autoantibodies by the mother, against antigens on fetal tissues, exposes the fetus to the risk of antibody-mediated perinatal disease. The biologic properties of immunoglobulins and the diseases that they produce are discussed. The use of laboratory tests to diagnose these diseases in high-risk women can minimize morbidity and mortality.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Clinics in Laboratory Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Abramson H.
        • Shur P.H.
        The IgG subclasses of red cell antibodies and relationship to monocyte binding.
        Blood. 1972; 40: 500
        • Augener W.
        • Grey H.M.
        • Cooper N.R.
        • et al.
        The reaction of monomeric and aggregated immunoglobulins with CI.
        Immunochem. 1971; 8: 1011
        • Baumann R.
        • Rubin H.
        Autoimmune hemolytic anemia during pregnancy, with hemolytic disease of the newborn.
        Blood. 1973; 41: 293
        • Bhatia H.M.
        • Sathe M.
        • Gandhi S.
        Differences between Bombay and Rhnull phenotypes.
        Vox Sang. 1974; 26: 272
      1. Borner, P., Deicher, H., Heide, K., et al.: Evidence for the participation of the Fc portion of immunoglobulin G in maternofetal immunoglobulin transfer in the human. Int. Congress Immunol. Obstet. Gynecol., 1973, p. 272

        • Bucher K.A.
        • Patterson A.M.
        • Elston R.C.
        Racial difference in incidence of ABO hemolytic diseases.
        Public Health. 1976; 66: 854
        • Chan-Shu S.Y.A.
        • Blair O.
        ABO hemolytic disease of the newborn.
        Am. J. Clin. Pathol. 1979; 71: 677
        • Chaplin H.
        • Cohen R.
        • Bloomberg G.
        • et al.
        Pregnancy and idiopathic autoimmune haemolytic anaemia: A prospective study during 6 months gestation and 3 months post partum.
        Br. J. Haematol. 1973; 24: 219
        • Ciccimarra F.
        • Rosen F.S.
        • Merler E.
        Localization of the IgG effector site for monocyte receptors.
        Proc. Natl. Acad. Sci. USA. 1975; 72: 2081
        • Dahr W.
        • Beyreuther K.
        • Steinbach H.
        • et al.
        Structure of the Ss blood group antigens, II: A methionine/threonine polymorphism within the N-terminal sequence of the Ss glycoprotein. Hoppe Seylers Z.
        Physiol. Chem. 1980; 361: 895
        • Davey M.G.
        • Zipursky A.
        McMaster conference on prevention of Rh immunization.
        Vox Sang. 1979; 36: 50
        • Dixon R.
        • Rosse W.
        • Ebbert L.
        Quantitative determination of antibody in idiopathic thrombocytopenic purpura: Correlation of serum and platelet bound antibody with clinical response.
        N. Engl. J. Med. 1975; 292: 230
        • Dufour D.R.
        • Monoghan W.P.
        ABO hemolytic disease of the newborn: A retrospective analysis of 254 cases.
        Am. J. Clin. Pathol. 1980; 73: 369
        • Elian S.B.
        • Butler I.
        • Appel S.H.
        Neonatal myasthenia in the infant of a myasthenic mother in remission.
        Ann. Neurol. 1979; 6: 72
        • Farre O.
        • Johnson P.M.
        • Froland S.S.
        • et al.
        Variably heavy chain (VH) subgroups of human antibody molecules: Comparison with IgG classes and light chain types.
        Clin. Immunol. Immunopathol. 1978; 9: 120
        • Farrell A.G.W.
        ABO incompatibility and hemolytic disease of the newborn.
        S. Afr. Med. J. 1970; 44: 211
        • Frankowska K.
        • Gorska B.
        IgG subclasses at Anti-Rh antibodies in pregnant women.
        Arch. Immunol. Ther. Exp. (Warsz.,). 1978; 26: 1095
        • Gitlin P.
        • Kumate J.
        • Urrusti J.
        • et al.
        The selectivity of the human placenta in the transfer of plasma proteins from mother to fetus.
        J. Clin. Invest. 1964; 43: 1938
        • Goodman J.
        • Wang A.C.
        Immunoglobulins: Structure diversity and genetics.
        in: Fudenberg H.H. Stites D.P. Caldwell J.L. Basic and Clinical Immunology. Edition 3. Lange, Los Altos, California1980: 28 (eds.)
        • Gorska B.
        • Frankowska K.
        In vitro reactions of anti-RH antibodies depending on the pattern of IgG subclasses.
        Arch. Immunol. Ther. Exp. (Warsz.). 1978; 26: 1101
        • Gratwohl A.A.
        • Shulman N.R.
        ABO-compatibilitat und isoimmune neonatale thrombopenie.
        Schweiz. Med. Wochenschr. 1977; 107: 1464
        • Gupte S.C.
        • Bhatia H.M.
        Increased incidence of hemolytic disease of the newborn caused by ABO incompatibility when tetanus toxoid is given during pregnancy.
        Vox Sang. 1980; 38: 22
        • Hardy J.D.
        • Solomon S.
        • Banwell G.S.
        • et al.
        Congenital complete heart block in the newborn associated with maternal systemic lupus erythematosus and other connective tissue disorders.
        Arch. Dis. Child. 1979; 54: 7
        • Henry R.A.
        • Weber J.
        • Pavone B.G.
        • et al.
        A “normal” individual with a positive direct antiglobulin test. Case complicated by pregnancy and unusual autoantibody specificity.
        Transfusion. 1977; 17: 539
        • Hershko C.
        • Berrebi A.
        • Resnitzky P.
        • et al.
        Relapsing hemolytic anemia of pregnancy with negative antiglobulin test.
        Scand. J. Haematol. 1976; 16: 135
        • Hughes-Jones N.C.
        • Hughes M. I.J.
        • Walker W.
        The amount of anti-D in red cells in haemolytic disease of the newborn.
        Vox Sang. 1967; 12: 279
        • Hughes-Jones N.C.
        • Ivona M.
        • Ellis J.
        • et al.
        Anti-D concentration in mother and child in haemolytic disease of the newborn.
        Vox Sang. 1971; 21: 135
        • Hughes-Jones N.C.
        • Hunt V.A.
        • Maycock W.
        • et al.
        Anti-D immunoglobulin preparations: The stability of anti-D concentrations and the error of the essay of anti-D.
        Vox Sang. 1978; 35: 100
        • Hunt J.S.
        • Beck M.L.
        • Hardmann J.T.
        • et al.
        Characterization of human erythrocyte to alloantibodies by IgG subclass and monocyte interaction.
        Am. J. Clin. Pathol. 1980; 74: 259
        • Issitt P.D.
        • Issitt C.H.
        Applied Blood Group Serology.Edition 2. Spectra Biologicals, Oxford, California1975: 338
        • Johnson B.J.
        • Thames K.E.
        Investigations of the complementing fixing sites of immunoglobulins.
        J. Immunol. 1976; JI7: 1491
        • Karpatkin S.
        • Schur P.H.
        • Strick N.
        • et al.
        Heavy chain subclass of human anti-platelet antibodies.
        Clin. Immunol. Immunopathol. 1973; 2: 1
        • Kehoe J.M.
        • Fougereau M.
        Immunoglobulin peptide with complement fixing activity.
        Nature. 1969; 224: 1212
        • Kelton J.
        • Blanchette V.S.
        • Wilson W.E.
        • et al.
        Neonatal thrombocytopenia due to passive immunization. Prenatal diagnosis and distinction between maternal alloantibodies and autoantibodies.
        N. Engl. J. Med. 1980; 302: 1401
        • Kirkman H.N.
        Further evidence for a racial difference in frequency of ABO hemolytic disease.
        J. Pediatr. 1977; 90: 717
        • Kohler P.F.
        • Farr R.S.
        Elevation of cord over maternal IgG immunoglobulin. Evidence for an active placental IgG transport.
        Nature. 1966; 210: 1070
        • Lalezari P.
        • Radel E.
        Neutrophil-specific antigens: Immunology and clinical significance.
        Semin. Hematol. 1974; 11: 281
        • Leeuwen E.F.
        • Van Krvon dem Borne A. E.G.
        • Oudesluijs-Murphy A.M.
        • et al.
        Neonatal alloimmune thrombocytopenia complicated by maternal autoimmune thrombocytopenia.
        Br. Med. J. 1980; 281: 27
        • Levine P.
        • Tripodi D.
        • Struck Jr., J.
        • et al.
        Hemolytic anemia associated with Rhnull but not with Bombay blood: A hypothesis based on differing antigenic structures.
        Vox Sang. 1973; 24: 417
        • Loghem J.J.
        • van der Meulen F.W.
        • Fleer A.
        • et al.
        The importance of the Fc receptor for red cell destruction under the influence of non-complement binding antibodies.
        in: Mohn J.F. Plankett R.W. Cunningham R.K. Human Blood Groups. Karger, Basel1977: 78 (eds.)
        • Low B.
        A practical method using papain and incomplete Rh-antibodies in routine Rh blood-grouping.
        Vox Sang. 1955; 5: 94
        • Masouradis S.P.
        • Sudora E.
        • Mahan L.
        • et al.
        Quantitative immunoferritin microscopy of Fya, Fyb, Jka, U and Dib antigen site numbers on human red cells.
        Blood. 1980; 56: 969
        • McKenzie J.M.
        • Zakarija M.
        Pathogenesis of neonatal Graves’ disease.
        J. Endocrinol. Invest. 1978; 2: 183
        • McNabb T.
        • Koh T.Y.
        • Dorrington K.J.
        • et al.
        Structure and function of immunoglobulin domains. V. Binding of immunoglobulin G and fragments to placental membrane preparations.
        J. Immunol. 1976; 117: 882
        • Mollison P.L.
        Blood Transfusion in Clinical Medicine. Edition 6. Blackwell Scientific, London1979
        • Moore B. P.L.
        • Humphries P.
        • Lovette-Moseley C.A.
        Serological and Immunological Methods of the Canadian Red Cross Blood Transfusion Service. Edition 7. Hunter Rose, Toronto1972: 71
        • Morell A.
        • Skvaril F.
        • van Loghem E.
        • et al.
        Human IgG subclasses in maternal and fetal serum.
        Vox Sang. 1971; 2i: 481
        • Ogra S.S.
        • Weintraub D.
        • Ogra P.L.
        Immunologic aspects of human colostrum and milk. III. Fate and absorption of cellular and soluble components in the gastrointestinal tract of the newborn.
        J. Immunol. 1977; 119: 245
        • Pearson H.A.
        • Shulman N.R.
        • Marder V.J.
        • et al.
        Isoimmune neonatal thrombocytopenic purpura: Clinical and therapeutic considerations.
        Blood. 1964; 23: 154
        • Peevy K.J.
        • Wiseman H.S.
        ABO hemolytic disease of the newborn: Evaluation of management and identification of racial and antigenic factors.
        Pediatrics. 1978; 61: 475
        • Pitkin R.M.
        Autoimmune diseases in pregnancy.
        Semin. Perinatol. 1971; 1: 161
        • Plauche W.C.
        Myasthenia gravis in pregnancy: An update.
        Am. J. Obstet. Gynecol. 1979; 135: 691
        • Porter R.R.
        The hydrolysis of rabbit globulin and antibodies with crystalline papain.
        Biochem. J. 1959; 73: 119
        • Puritz E.M.
        • Yount W.J.
        • Newell M.
        • et al.
        Immunoglobulin classes and IgG subclasses of human antinuclear antibodies. A correlation of complement fixation and the nephritis of systemic lupus erythematosus.
        Clin. Immunol. Immunopathol. 1973; 2: 98
        • Putnam F.W.
        Structural relationships between normal human globulin, myeloma globulins and Bence Jones proteins.
        Biochim. Biophys. Acta. 1962; 63: 539
        • Race R.R.
        • Sanger R.
        Blood Groups in Man. Edition 6. Blackwell Scientific, London1975
        • Romans D.G.
        • Tilley C.A.
        • Dorrington K.J.
        Interactions between Fab and Fc regions in liganded immunoglobulin G.
        Mol. Immunol. 1979; 16: 859
        • Romans D.G.
        • Tilley C.A.
        • Dorrington K.J.
        Monogamous bivalency of IgG antibodies. I. Deficiency of branched ABHI-active oligosaccharide chains on red cells of infants causes the weak antiglobulin reaction in hemolytic disease of the newborn due to ABO incompatibility.
        J. Immunol. 1980; 124: 2807
        • Rosenfield R.E.
        • Ohno G.
        A-B hemolytic disease of the newborn.
        Rev. Hemotol. 1955; 10: 231
        • Santheimer R.D.
        • Gilliam J.N.
        DNA antibody class, subclass and complement fixation in systemic lupus erythematosus with and without nephritis.
        Clin. Immunol. Immunopathol. 1978; 10: 459
        • Schanfield M.S.
        Immunoglobulin haplotypes in Tlaxcaltecan and other populations.
        in: Crawford M.H. The Tlaxcaltecans. University of Kansas Press, Lawrence, Kansas1976: 150
        • Schanfield M.S.
        Human immumoglobulin (IgG) subclasses and their biological properties.
        in: Blood Bank Immunology. American Association of Blood Banks, Washington, D.C1977: 97
        • Schanfield M.S.
        Immunoglobulins: Genetic markers.
        in: Fudenberg H.H. Stites D.P. Caldwell J.L. Basic and Clinical Immunology. Lange, Los Altos, California1980: 79 (eds.)
      2. Schanfield, M. S.: Immunoglobulin subclass as a determinant of severity in Rh hemolytic disease of the newborn. In preparation

        • Schanfield M.S.
        • Marguelies M.
        Interrelation entre las subclases de IgG y el desarrollo clinico de la enfermedad hemolotica neonatal.
        Rev. Argent. Transfusion. 1979; 3: 83
        • Schanfield M.S.
        • Schoeppner S.L.
        • Stevens J.O.
        New approaches to detecting clinically significant antibodies in the laboratory.
        in: Sandler S.G. Nusbacher J. Schanfield M.S. Immunobiology of the Erythrocyte. Alan R. Liss, Inc., New York1980: 305
      3. Schanfield, M. S, and Schoeppner, S. L.: Additional studies on the IgG subclass of red cell antibodies, relationship to mononuclear phagocyte binding and clinical significance. In preparation

        • Schur P.H.
        • Alpert E.
        • Alper C.
        Gamma g subgroups in human fetal, cord and maternal sera.
        Clin. Immunol. Immunopathol. 1973; 2: 62
        • Scott J.R.
        • Cruikshank D.P.
        • Kochenour N.K.
        • et al.
        Fetal platelet counts in the obstetric management of immunologic thrombocytopenic purpura.
        Am. J. Obstet. Gynecol. 1980; 136: 495
        • Shulman N.R.
        • Marder V.J.
        • Hiller M.C.
        • et al.
        Platelet and leukocyte isoantigens and their antibodies: Serologic, physiologic and clinical studies.
        Prog. Hematol. 1964; 4: 22
        • Sitarz A.L.
        • Driscoll J.M.
        • Wolff J.A.
        Management of isoimmune neonatal thrombo cytopenia.
        Am. J. Obstet. Gynecol. 1976; 124: 39
        • Speigelberg A.L.
        Biological activities of immunoglobulins of different classes and subclasses.
        Adv. Immunol. 1974; 19: 259
        • Stefanini M.
        • Mele R.H.
        • Skinner D.
        Transitory congenital neutropenia: A new syndrome.
        Am. J. Med. 1958; 25: 749
        • Sturgeon P.
        Hematological observations in the anemia associated with blood type Rhnun.
        Blood. 1970; 36: 310-320
        • Svejgaard A.
        Iso-antigenic systems of human blood platelets: A survey.
        J. Hematol. 1969; 2: 3
      4. Systemic lupus in the newborn (letter).
        Lancet. 1979; 8121: 859
        • Territo M.
        • Finklestein J.
        • Oh J.
        • et al.
        Management of autoimmune thrombocytopenia in pregnancy and the neonate.
        Obstet. Gynecol. 1973; 41: 579
        • Tokunaga E.
        • Sasakawa S.
        • Tamaka K.
        • et al.
        Two apparently healthy Japanese individuals of type MkMk have erythrocytes which lack both the blood group MN and SS active sialoglycoproteins.
        J. Immunogenet. 1979; 6: 383
        • Tomasi T.B.
        • McNabb P.C.
        The secretory immune system.
        in: Fudenberg H.H. Stites D.P. Caldwell J.L. Basic and Clinical Immunology. Edition 3. Lange Medical Publisher, Los Altos, California1980: 240 (eds.)
        • Vain N.E.
        • Bedros A.A.
        Treatment of isoimmune thrombocytopenia of the newborn with transfusion of maternal platelets.
        Pediatrics. 1979; 63: 107
        • Vanderheid E.C.
        • Koblenzer P.J.
        • Ming P. M.L.
        • et al.
        Neonatal lupus erythematosus.
        Arch. Dermatol. 1976; 112: 698
        • Verheugt F. W.A.
        • von dem Borne A.E.G.
        • Noord-Bokhorst J.C.
        • et al.
        Serological, immunochemical and immunocytological properties of granulocyte antibodies.
        Vox Sang. 1978; 35 (v.): 294
        • Verheugt F. W.A.
        • Noord-Bokhorst J.C.
        • von dem Borne A. E.G.
        • et al.
        A family with alloimmune neonatal neutropenia: Group specific pathogenicity of maternal antibodies.
        Vox Sang. 1979; 36 (v.): 1
        • Walker W.
        The changing pattern of haemolytic disease of the newborn (1948-1959).
        Vox Sang. 1958; 3: 225
        • Wang A.C.
        • Faulk W.P.
        • Stuckey M.A.
        • et al.
        Chemical differences of adult, fetal and hypogammaglobulinemic IgG immunoglobulins.
        Immunochem. 1970; 7: 703
        • Wennberg R.P.
        • Depp R.
        • Heinrichs W.L.
        Indications for early exchange transfusions in patients with erythroblastosis fetalis.
        J. Pediatr. 1978; 92: 789
        • Wimer B.M.
        • Marsh W.L.
        • Taswell H.F.
        • et al.
        Haematological changes associated with the McLeod phenotype of the Kell blood group system.
        Br. J. Haematol. 1977; 36: 219
        • Winkelhake J.L.
        Immunoglobulin structure and effector functions.
        Immunochem. 1978; 15: 695
        • Wykowski P.K.
        • Flynt J.W.
        • Goldberg M.F.
        • et al.
        Rh hemolytic disease: Epidemiologic surveillance in the United States, 1968 to 1975.
        J.A.M.A. 1979; 242: 1376
        • Yam P.
        • Wilkinson L.
        • Petz L.D.
        • et al.
        Studies on hemolytic anemia in pregnancy with evidence for autoimmunization in a patient with a negative direct antiglobulin (Coombs) test.
        Am. J. Hematol. 1980; 8: 23
        • Zulman J.
        • Talal N.
        • Hoffman G.S.
        • et al.
        Problems associated with the management of pregnancies in patients with systemic lupus erythematosus.
        J. Rheumatol. 1979; 7: 37