The management of alloimmune neonatal thrombocytopenia

Blanchette, Victor S.; Johnson, Jo‐Ann; Rand, Margaret L.

doi:10.1053/beha.2000.0083

Cited by 92 publications

(85 citation statements)

References 126 publications

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“…Persisting fetal7maternal microchimerism has also been invoked because of the recent findings of fetal or maternal RNA in scleroderma lesions (discussed in Maloney et al, 1999;Nelson, 2001). There are already well-known examples of alloimmunization of mothers, for example, by fetal erythrocytes or platelets (Blanchette et al, 2000). Although it might be informative to look for allotypic variations in the AChR ␥ subunit, the AChR is remarkably autoimmunogenic, even without adjuvant (Jermy et al, 1993).…”

Section: Fetal-specific Abs In Arthrogryposismentioning

confidence: 99%

Antibodies to Acetylcholine Receptor in Parous Women with Myasthenia: Evidence for Immunization by Fetal Antigen

Matthews

Sims

Ledwidge

et al. 2002

Laboratory Investigation

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SUMMARY:The weakness in myasthenia gravis (MG) is mediated by autoantibodies against adult muscle acetylcholine receptors (AChR) at the neuromuscular junction; most of these antibodies also bind to fetal AChR, which is present in the thymus. In rare cases, babies of mothers with MG, or even of asymptomatic mothers, develop a severe developmental condition, arthrogryposis multiplex congenita, caused by antibodies that inhibit the ion channel function of the fetal AChR while not affecting the adult AChR. Here we show that these fetal AChR inhibitory antibodies are significantly more common in females sampled after pregnancy than in those who present before pregnancy, suggesting that they may be induced by the fetus. Moreover, we were able to clone high-affinity combinatorial Fab antibodies from thymic cells of two mothers with MG who had babies with arthrogryposis multiplex congenita. These Fabs were highly specific for fetal AChR and did not bind the main immunogenic region that is common to fetal and adult AChR. The Fabs show strong biases to VH3 heavy chains and to a single V1 light chain in one mother. Nevertheless, they each show extensive intraclonal diversification from a highly mutated consensus sequence, consistent with antigen-driven selection in successive steps. Collectively, our results suggest that, in some cases of MG, initial immunization against fetal AChR is followed by diversification and expansion of B cells in the thymus; maternal autoimmunity will result if the immune response spreads to the main immunogenic region and other epitopes common to fetal and adult AChR. (Lab

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Section: Fetal-specific Abs In Arthrogryposismentioning

confidence: 99%

Antibodies to Acetylcholine Receptor in Parous Women with Myasthenia: Evidence for Immunization by Fetal Antigen

Matthews

Sims

Ledwidge

et al. 2002

Laboratory Investigation

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“…They may become immunized against HPA 1a during pregnancy if the fetus is HPA 1a positive. 1 Maternal IgG antibodies against HPA 1a can traverse placenta and sensitize the fetal platelets, leaving the fetus thrombocytopenic and at risk of bleeding.…”

Section: Introductionmentioning

confidence: 99%

A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia

Kjeldsen‐Kragh

Killie²,

Tomter³

et al. 2007

Blood

240

277

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The study's objective was to identify HPA 1a-negative women and to offer them an intervention program aimed to reduce morbidity and mortality of neonatal alloimmune thrombocytopenia (NAIT). HPA 1 typing was performed in 100 448 pregnant women. The HPA 1a-negative women were screened for anti-HPA 1a. In immunized women, delivery was performed by Cesarean section 2 to 4 weeks prior to term, with platelets from HPA 1a-negative donors reserved for immediate transfusion if petechiae were present and/or if platelet count was less than 35 ؋ 10 9 /L. Of the women screened, 2.1% were HPA 1a negative, and anti-HPA 1a was detected in 10.6% of these. One hundred seventy pregnancies were managed according to the intervention program, resulting in 161 HPA 1a-positive children. Of these, 55 had severe thrombocytopenia (< 50 ؋ 10 9 /L), including 2 with intracranial hemorrhage (ICH). One woman with a twin pregnancy missed the follow-up and had one stillborn and one severely thrombocytope-

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“…Neonatal alloimmune thrombocytopenia (NAIT) in Caucasians is most commonly due to transplacental passage of maternal anti-HPA 1a antibodies (85%), 1 and is a condition that resembles hemolytic disease of the newborn. Complications of NAIT, such as intracranial hemorrhage, leading to neurological disability or death, have been reported to occur in 10-30% of affected babies.…”

Section: Introductionmentioning

confidence: 99%

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

Killie¹,

Husebekk²,

et al. 2008

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The management of alloimmune neonatal thrombocytopenia

Cited by 92 publications

References 126 publications

Antibodies to Acetylcholine Receptor in Parous Women with Myasthenia: Evidence for Immunization by Fetal Antigen

Antibodies to Acetylcholine Receptor in Parous Women with Myasthenia: Evidence for Immunization by Fetal Antigen

A screening and intervention program aimed to reduce mortality and serious morbidity associated with severe neonatal alloimmune thrombocytopenia

A prospective study of maternal anti-HPA 1a antibody level as a potential predictor of alloimmune thrombocytopenia in the newborn

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