Compound heterozygosity of HLA‐DRB3*01:01 and HLA‐DRB4*01:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia

Loewenthal, Ron; Rosenberg, Nurit; Kalt, Rivka; Dardik, Rima; Landau, Meytal; Yahalom, Vered; Avishai, Ophelia; Frenkel, Orit; Gazit, Ephraim; Steinberg, David M.; Lipitz, Shlomo; Salomon, Ophira

doi:10.1111/j.1537-2995.2012.03734.x

Cited by 28 publications

(36 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, HLA‐DQB1*02:01 was overrepresented in anti‐HPA‐1a–alloimmunized women probably because of linkage disequilibrium with HLA‐DRB3*01:01 . Recently, Loewenthal and coworkers showed that HLA‐DRB4*01:01P also binds the HPA‐1a epitope leading to an immune response. Nevertheless, the model of HLA‐DRB4*01:01P crystal structure published by the authors shows that the binding cavity of this variant is less hydrophobic than that of HLA‐DRB3*01:01.…”

Section: Discussionmentioning

confidence: 99%

“…In 90% of cases of HPA‐1a fetomaternal alloimmunizations, the mother carries this HLA Class II molecule . Recently, Loewenthal and colleagues suggested that HLA‐DRB4*01:01 also plays a role in HPA‐1a peptide presentation. They observed that the combination of both DRB3*01:01 and DRB4*01:01 antigens was associated with more severe cases of FNAIT and affects response to antenatal treatment with IVIG.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage

et al. 2015

View full text Add to dashboard Cite

BACKGROUND In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most frequently caused by maternal alloimmunization against the human platelet antigen HPA‐1a. The most serious complication of severe FNAIT is intracranial hemorrhage (ICH). ICH mainly occurs in utero; therefore, there is a need to identify noninvasive predictive factors of ICH to facilitate early identification of this condition and to determine response to maternal therapy. STUDY DESIGN AND METHODS We studied gynecologic and immunogenetic variables of severe cases of anti‐HPA‐1a FNAIT within three groups: Group I, FNAIT without ICH; Group II, FNAIT with ICH; and Group III, suspected FNAIT cases without detectable maternal anti‐HPA‐1a alloantibodies. RESULTS ICH was associated with a poor outcome because it led to death in 59% of cases. Multigravida (two or more pregnancies) was overrepresented in Group II, consistent with the high concentrations of maternal HPA‐1a alloantibody and the frequent detection of a strong newborn‐specific HLA class I antibody response at delivery. The proportion of HLA‐DRB4*01:01P (*01:01 or *01:03) women was similar in Groups I and II, but this allele was overrepresented in Group III, in which FNAIT was less severe than in the other two groups. Finally, antenatal intravenous immunoglobulin therapy tended to be more effective in HLA‐DRB3*01:01(+)/HLA‐DRB4*01:01P(+) women than for HLA‐DRB3*01:01(+)/HLA‐DRB4*01:01P(–) women. CONCLUSION The number of gestations is a predictive factor of ICH in anti‐HPA‐1a–alloimmunized women. Maternal immunogenetic variables should be investigated in the context of maternal immunization and may predict response to maternal therapy in subsequent pregnancies.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage

et al. 2015

View full text Add to dashboard Cite

show abstract

“…HPA‐1a antibodies are the cause of the majority (~85%) of serologically confirmed FNAIT cases, in which a maternal platelet‐specific antibody is detected (Table ). Immunization to HPA‐1a is highly correlated with carrying the class II human leucocyte antigen (HLA), HLA‐DRB3*0101 , and more recently HLA‐DRB4*01:01 . The lower frequency HPA‐1b antigen is more commonly expressed in Caucasian populations, and individuals with the HPA‐1b/1b platelet type are those that can make HPA‐1a antibodies.…”

Section: Human Platelet Alloantigensmentioning

confidence: 99%

Human platelet antigens – 2013

2013

View full text Add to dashboard Cite

To date, 33 human platelet alloantigens (HPAs) have been identified on six functionally important platelet glycoprotein (GP) complexes and have been implicated in alloimmune platelet disorders including foetal and neonatal alloimmune thrombocytopenia (FNAIT), posttransfusion purpura (PTP) and multitransfusion platelet refractoriness (MPR). The greatest number of recognized HPA (20 of 33) resides on the GPIIb/IIIa complex, which serves as the receptor for ligands important in mediating haemostasis and inflammation. These include HPA-1a, the most commonly implicated HPA in FNAIT and PTP in Caucasian populations. Other platelet GP complexes, GPIb/V/IX, GPIa/IIa and CD109, express the remaining 13 HPAs. Of the recognized HPAs, 12 occur as six serologically and genetically defined biallelic 'systems' where the -a form designates the higher frequency allele and the -b form, the lower. Twenty-one other HPAs are low-frequency or rare antigens for which postulated higher frequency -a alleles have not yet been identified as antibody specificities. In addition to the HPA markers, platelets also express ABO and human leucocyte antigen (HLA) antigens; antibodies directed at the former are occasionally important in FNAIT, and to the latter, in MPR.

show abstract

“…116,159,160 The most plausible explanation for this may be the strong association between the human leucocyte antigen (HLA) class II DRB3*0101 and DRB4*0101 alleles and HPA-1a alloantibody generation. 155 The DRB3 allele has also been demonstrated to have binding affinity for HPA-1a but not HPA-1b. 154 This implies that specific maternal antigen presentation pathway and a specific genetic background may be involved in fetal antigen alloimmunization.…”

Section: Mechanisms Of Alloantibody Generation In Fnaitmentioning

confidence: 99%

Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

et al. 2015

View full text Add to dashboard Cite

Platelets play critical roles in hemostasis and thrombosis. Emerging evidence indicates that they are versatile cells and also involved in many other physiological processes and disease states. Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life threatening bleeding disorder caused by fetal platelet destruction by maternal alloantibodies developed during pregnancy. Gene polymorphisms cause platelet surface protein incompatibilities between mother and fetus, and ultimately lead to maternal alloimmunization. FNAIT is the most common cause of intracranial hemorrhage in full-term infants and can also lead to intrauterine growth retardation and miscarriage. Proper diagnosis, prevention and treatment of FNAIT is challenging due to insufficient knowledge of the disease and a lack of routine screening as well as its frequent occurrence in first pregnancies. Given the ethical difficulties in performing basic research on human fetuses and neonates, animal models are essential to improve our understanding of the pathogenesis and treatment of FNAIT. The aim of this review is to provide an overview on platelets, hemostasis and thrombocytopenia with a focus on the advancements made in FNAIT by utilizing animal models.

show abstract

Compound heterozygosity of HLA‐DRB301:01 and HLA‐DRB401:01 as a potential predictor of fetal neonatal alloimmune thrombocytopenia

Abstract: Overall, we suggest that a specific genotyping of the mother in relation to HLA-DRB as well as HPA-1 can serve as an antenatal diagnostic tool, particularly in siblings of women who gave birth to neonates with FNAIT.

Cited by 28 publications

References 29 publications

Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage

Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage

Human platelet antigens – 2013

Platelets and platelet alloantigens: Lessons from human patients and animal models of fetal and neonatal alloimmune thrombocytopenia

Contact Info

Product

Resources

About