HLA association is different in children and adults with severe acquired aplastic anemia.

BACKGROUND: Severe aplastic anemia (SAA) is defined as pancytopenia caused by bone marrow failure. The pathogenesis of SAA is thought to involve autoimmune processes. Increased susceptibility to autoimmunity has been shown to be associated with several different HLA alleles. In SAA, few large studies based on data mainly from adults describe a positive HLA correlation with HLA-DR2 (DRB1*15) and HLA-B14. PROCEDURE: This study explored the HLA constitution of 181 children with SAA who were enrolled in the prospective multi-center study SAA94 between January 1994 and January 2002. The control group consisted of 303 healthy individuals of comparable demographic background. Allelic frequencies between patients and controls are compared using Fisher's exact test. RESULTS: In our pediatric cohort, we describe a positive association with HLA-B14 (P = 0.0039), but no association of HLA-DR2 with SAA. CONCLUSION: HLA associations appear to be different in children and adults with SAA. This might point towards a difference in pathophysiology between at least part of the children and adults.

High-risk pregnancies in Diamond-Blackfan anemia: a survey of 64 pregnancies from the French and German registries.

We reviewed 64 pregnancies in 26 women with Diamond-Blackfan anemia (DBA) included in the French and German DBA registries. Complications were seen in 42 pregnancies (66%) and included abortion, pre-eclampsia, in utero fetal death, intrauterine growth retardation, retroplacental hematoma, pre-term delivery and fetal malformations. Of the 34 children (53%) born alive, 13 had DBA. No correlations were found between pregnancy outcome and features of either maternal or child DBA. Pregnancies in DBA-affected women are at high risk, especially for complications likely to be of vascular-placental origin. Careful monitoring with prevention of severe anemia and early introduction of aspirin is suggested.

Macrophages of patients with X-linked thrombocytopenia display an attenuated Wiskott-Aldrich syndrome phenotype.

The immunodeficiency disorder Wiskott-Aldrich syndrome and its milder form X-linked thrombo-cytopenia are caused by mutations in the WASp gene. Wiskott-Aldrich syndrome is characterized by a plethora of clinical symptoms which are due to functional defects of haematopoietic cells, including the inability of macrophages to form actin-rich adhesion structures called podosomes. In contrast, X-linked thrombocytopenia patients show reduced platelet size and counts but no cytoskeletal white blood cell defects have been detected so far. Here we use immunofluorescence technique to evaluate podosome formation in macrophages from X-linked thrombocyto-penia and Wiskott-Aldrich syndrome patients and from healthy donors. We find that X-linked thrombocytopenia macrophages, cells previously thought to be unaffected in this disorder, are compromised in the formation of podosomes. Western blot analysis shows that this phenotype is not due to lower levels of WASp expression. Interestingly, the bacterial chemoattractant formyl-methionyl-leucyl-phenylalanine can rescue podosome formation in X-linked thrombocytopenia cells. Our findings indicate that: 1. The spectrum of WASp-dependent disorders contains defects more subtle than originally recognized and 2. in X-linked thrombocytopenia, some of these defects may not be evident under conditions of bacterial stimulation. Further evaluation of this and other, as yet unrecognized, cellular defects may provide a more complete picture of the continuum of Wiskott-Aldrich syndrome and X-linked thrombocytopenia defects.