A new platelet alloantigen, Swia, located on glycoprotein Ia identified in a family with fetal and neonatal alloimmune thrombocytopenia
Corresponding Author
Hartmut Kroll
Hartmut Kroll, MD, Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, 06847 Dessau, Germany; e-mail: [email protected]. Search for more papers by this authorKorinna Feldmann
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorClaudia Zwingel
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorJochen Hoch
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorRainer Bald
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorGregor Bein
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorBehnaz Bayat
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorSentot Santoso
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorCorresponding Author
Hartmut Kroll
Hartmut Kroll, MD, Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, 06847 Dessau, Germany; e-mail: [email protected]. Search for more papers by this authorKorinna Feldmann
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorClaudia Zwingel
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorJochen Hoch
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorRainer Bald
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorGregor Bein
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorBehnaz Bayat
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorSentot Santoso
From the Institute for Transfusion Medicine Dessau, Red Cross Blood Transfusion Service NSTOB, Dessau; the Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen; the Institute for Experimental Hematology and Transfusion Medicine, Bonn; and the Department for Prenatal Medicine, Clinics for Gynaecology and Obstetrics, Leverkusen, Germany.
Search for more papers by this authorAbstract
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by transplacental passage of maternal antibodies to fetuses whose platelets (PLTs) express the corresponding human PLT antigen (HPA).
STUDY DESIGNS AND METHODS: We observed a fetus with FNAIT who died from a severe intracranial hemorrhage. Analysis of maternal serum in antigen capture assay with paternal PLTs showed reactivity with PLT glycoprotein (GP)IIb/IIIa (αIIbβ3) and GPIa/IIa (α2β1 integrin), indicating the presence of anti-HPA-1a and an additional alloantibody against GPIa (termed anti-Swia).
RESULTS: By immunochemical studies, the localization of the Swia antigen on GPIa/IIa could be confirmed. Analysis of paternal GPIa full-length cDNA showed a single-nucleotide substitution C3347T in Exon 28 resulting in a Thr1087Met amino acid substitution. Testing of family members by polymerase chain reaction-restriction fragment length polymorphism using MslI endonuclease showed perfect correlation with phenotyping. Extended family and population studies showed that 4 of 10 members of the paternal family but none of 500 unrelated blood donors were Swia carriers. Expression studies on allele-specific transfected Chinese hamster ovary (CHO) cells confirmed that the single-amino-acid substitution Thr1087Met was responsible for the formation of the Swia epitope. Adhesion of CHO cells expressing the Swia alloantigen to immobilized collagens was not impaired compared to the wild-type control and was not inhibited by anti-Swia alloantibodies.
CONCLUSION: In this study we defined a new PLT alloantigen Swia that was involved in a case of additional immunization against HPA-1a. Our observations demonstrate that combinations of PLT-specific alloantibodies may comprise low-frequency alloantigens.
REFERENCES
- 1 Kaplan C. Foetal and neonatal alloimmune thrombocytopenia. Orphanet J Rare Dis 2006; I: 39.
- 2
Mueller-Eckhardt C,
Kiefel V,
Grubert A,
Kroll H,
Weisheit M,
Schmidt S,
Mueller-Eckhardt G,
Santoso S.
348 cases of suspected neonatal alloimmune thrombocytopenia.
Lancet
1989; I: 363-6.
10.1016/S0140-6736(89)91733-9 Google Scholar
- 3 Davoren A, Curtis BR, Aster RH, McFarland JG. Human platelet antigen-specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia. Transfusion 2004; 44: 1220-5.
- 4 Ertel K, Al-Tawil M, Santoso S, Kroll H. Relevance of the HPA-15 (Gov) polymorphism on CD109 in alloimmune thrombocytopenic syndromes. Transfusion 2005; 45: 366-73.
- 5 Kroll H, Kiefel V, Santoso S, Mueller-Eckhardt C. Sra, a private platelet antigen on glycoprotein IIIa associated with neonatal alloimmune thrombocytopenia. Blood 1990; 76: 2296-302.
- 6 Zutter MM, Edelson BT. The α2β1 integrin: a novel collectin/C1q receptor. Immunobiology 2007; 212: 343-53.
- 7 Santoso S, Kalb R, Kiefel V, Mueller-Eckhardt C, Newman PJ. The human platelet alloantigens Bra and Brb are associated with a single amino acid polymorphism on glycoprotein Ia (integrin α2 subunit). J Clin Invest 1993; 92: 2427-32.
- 8 Santoso S, Kunicki TJ, Kroll H, Haberbosch W, Gardemann A. Association of the platelet glycoprotein Ia C807T gene polymorphism with myocardial infarction in younger patients. Blood 1999; 93: 2449-53.
- 9 Santoso S, Amrhein J, Hofmann H, Sachs U, Walka M, Kroll H, Kiefel V. A mutational hot spot Thr799Met on the α2 integrin subunit leads to the formation of the new human platelet alloantigen Sita and affects collagen-induced aggregation. Blood 1999; 94: 4103-11.
- 10 Bertrand G, Jallu V, Saillant D, Kervran D, Martageix C, Kaplan C. The new platelet alloantigen Caba: a single point mutation Gln716His on the α2 integrin. Transfusion 2009; 49: 2076-83.
- 11 Kritzik M, Savage B, Nugent D, Santoso S, Ruggeri ZM, Kunicki TJ. Nucleotide polymorphisms in the α2 gene define multiple alleles that are associated with differences in platelet α2β1 density. Blood 1998; 92: 2382-8.
- 12 Koh Y, Taniue A, Ishii H, Matsuyama N, Amakishi E, Hayashi T, Furata RA, Fukumori Y, Hirayama F, Yoshimura K, Nagamine T, Tamai S, Nakano S. Neonatal alloimmune thrombocytopenia caused by an antibody specific for a newly identified allele of human platelet antigen-7. Transfusion 2010; 50: 1276-84.
- 13 Kuijpers RW, Simsek S, Faber NM, Goldschmeding R, van Wermerkerken RK, von dem Borne AE. Single point mutation in human glycoprotein IIIa is associated with a new platelet-specific alloantigen (Mo) involved in neonatal alloimmune thrombocytopenia. Blood 1993; 81: 70-6.
- 14 Santoso S, Kroll H, Andrei-Selmer CL, Socher I, Rankin A, Kretzschmar E, Watkins NA, Ouwehand WH. A naturally occuring Leu33Val mutation in β3-integrin impairs the HPA-1a epitope: the third allele of HPA-1. Transfusion 2006; 46: 790-9.
- 15 Peterson JA, Gitter ML, Pietz B, Bellissimo DB, Curtis BR, Aster RH. A third allele of the HPA-5 (Br) platelet alloantigen system identified in investigating a case of neonatal thrombocytopenia. Transfusion 2010; 50: 1855-6.
- 16 Kiefel V. The MAIPA assay and its applications in immunohaematology. Transfus Med 1992; 2: 181-8.
- 17 Santoso S, Kalb R, Kroll H, Walka M, Kiefel V, Mueller-Eckhardt C, Newman PJ. A point mutation leads to an unpaired cysteine residue and a molecular weight polymorphism of a functional platelet beta3 integrin subunit. J Biol Chem 1994; 269: 8439-44.
- 18 Carl B, Kroll H, Bux J, Bein G, Santoso S. B-lymphoblastoid cell lines as source of reference DNA for genotyping of human platelet and neutrophil antigens. Transfusion 2000; 40: 62-8.
- 19 Antonarakis SE. Recommendations for a nomenclature system for human gene mutations. Nomenclature Working Group. Hum Mutat 1998; 11: 1-3.
- 20 Emsley J, King SL, Bergelson JM, Liddington RC. Crystal structure of the I domain from integrin α2β1. J Biol Chem 1997; 272: 28512-7.
- 21 Kunicki TJ, Kritzik M, Annis DS, Nugent DJ. Hereditary variation in platelet integrin α2β1 density is associated with two silent polymorphisms in the α2 gene coding sequence. Blood 1997; 89: 1939-43.
- 22 Kroll H, Yates J, Santoso S. Immunization against a low-frequency human platelet alloantigen in fetal alloimmune thrombocytopenia is not a single event: characterization by the combined use of reference DNA and novel allele-specific cell lines expressing recombinant antigens. Transfusion 2005; 45: 353-8.
- 23 Kaplan C, Morel-Kopp MC, Kroll H, Kiefel V, Schlegel N, Chesnel N, Mueller-Eckhardt C. HPA-5b (Bra) neonatal alloimmune thrombocytopenia: clinical and immunological analysis of 39 cases. Br J Haematol 1991; 78: 425-9.
- 24 Ghevaert C, Rankin A, Huiskes E, Porcelijn L, Javela K, Kekomäki R, Bakchoul T, Santoso S, Nutland S, Smyth DJ, Smith GA, McBride S, Watkins NA, Ouwehand WH. Alloantibodies against low-frequency human platelet antigens do not account for a significant proportion of cases of fetomaternal alloimmune thrombocytopenia: evidence from 1054 cases. Transfusion 2009; 49: 2084-9.
- 25 Peterson JA, Balthazr SM, Curtis BR, McFarland JG, Aster RH. Maternal alloimmunization against the rare platelet-specific antigen HPA-9b (Maxa) is an important cause of neonatal alloimmune thrombocytopenia. Transfusion 2005; 45: 1487-95.
- 26 Peterson JA, Gitter ML, Kanack A, Curtis BR, McFarland JG, Bougie D, Aster RH. New low-frequency platelet glycoprotein polymorphisms associated with neonatal alloimmune thrombocytopenia. Transfusion 2010; 50: 324-33.