Hydrops fetalis associated with anti‐CD36 antibodies in fetal and neonatal alloimmune thrombocytopenia: Possible underlying mechanism

Abstract

Objectives: In the present study, we asked whether anti-CD36 antibodies impair the maturation of erythropoietic stem cells to mature red blood cells (RBCs), leading to anaemia and hydrops fetalis (HF). Background: Recent studies have shown the importance of anti-CD36 antibodies in the development of Fetal/Neonatal Alloimmune Thrombocytopenia (FNAIT). In comparison to other types of antibody-mediated FNAIT, anti-CD36 antibodies are frequently associated with anaemia and HF. As mature RBCs do not express CD36, the reason for this phenomenon is currently not fully understood. Material and methods: A case of FNAIT with signs of HF was characterised in this study. Maternal anti-CD36 antibodies were isolated by an absorption/elution approach. We cultured haematopoietic stem cells (HSCs) with purified anti-CD36 antibodies, and the formation of burst-forming unit-erythroid and colony-forming unit-erythroid (CFU-E/BFU-E) cells was analysed. Apoptosis of HSCs was also investigated. Results: Analysis of the mother showed type-1 CD36 deficiency. Anti-CD36 antibodies were found in maternal serum, as well as on fetal platelets, by ELISA, and the specificity of these antibodies was further substantiated by flow cytometry. In comparison to control IgG, incubation of HSCs with purified anti-CD36 antibodies led to a significant reduction in CFU-E/BFU-E cell formation, and this result was associated with an increased number of apoptotic CD34+ erythroid/myeloid precursor cells. Administration of intrauterine transfusion with washed RBCs was effective in improving fetal anaemia. Conclusions: Anti-CD36 antibodies may cause anaemia and trigger HF through apoptosis of CD34+ erythroid/myeloid precursor cells. However, the contribution of other cells must also be taken into account.

Platelet CD36 deficiency is present in 2.6% of Arabian individuals and can cause NAIT and platelet refractoriness

“…On the contrary, isoantibodies to the high‐frequency CD36 antigen are virtually unknown within Middle European countries 4 . However, in Eastern Asia and Africa South of Sahara, CD36 isoantibodies repeatedly have been reported to induce NAIT, platelet refractoriness, PTP, and passively transferred thrombocytopenia 4–9 . It is challenging for European blood services to provide compatible platelet concentrates for patients originating from these regions as the respective ethnicities are mostly underrepresented within the blood donor population.…”

Successful prenatal therapy for anti-CD36-mediated severe FNAIT by deglycosylated antibodies in a novel murine model

“…Compared with anti-HPA-1a, anti-CD36 antibodies cause more common hydrops and recurrent miscarriages. 16,20,21 The reason for this phenomenon is unknown. Therefore, the current approach for treating FNAIT caused by anti-HPA-1a may not be adaptable for the disease caused by anti-CD36 antibodies.…”

Diagnostik und Therapie einer Anti-CD36-induzierten neonatalen Alloimmunthrombozytopenie

“…Anti-CD36 kann schwere Komplikationen bis zum Hydrops fetalis auslösen [25,27], wobei ein möglicher Mechanismus in der erhöhten Anzahl apoptotischer CD34+ erythroider/myeloider Vorläuferzellen bestehen könnte, an welche der Antikörper ebenfalls bindet. Generell wird das Risiko einer FNAIT in der Folgeschwangerschaft mindestens so hoch angesehen wie in der Erstschwangerschaft, sodass Folgeschwangerschaften in spezialisierten Pränatalzentren betreut werden sollten [1].…”

“…Einige CD36-Isoantikörper-vermittelte FNAIT-Fälle mit milden bis schweren Verläufen einschließlich Hydrops fetalis mit Todesfolge wurden bei Neugeborenen asiatischer oder afrikanisch-amerikanischer Abstammung berichtet [22,25]. Insbesondere in asiatischen Populationen scheint die FNAIT sogar bevorzugt mit Anti-CD36, früher auch als Anti-Nak a bezeichnet, assoziiert zu sein [25 -28].…”