RESUMEN
OBJECTIVES: To investigate the specificities and level of HLA class I antibodies in selected cases referred for suspected foetal and neonatal alloimmune thrombocytopenia (FNAIT). BACKGROUND: FNAIT occurs in 1 : 1-2000 live births, whereas maternal immunisation against human leukocyte antigen (HLA) class I is common. Whether HLA class I antibodies alone can cause FNAIT is debatable. MATERIAL AND METHODS: A total of 260 patient samples were referred between 2007 and 2012. Referrals with maternal HLA class I antibodies and no other cause for the neonatal thrombocytopenia were included for analysis (cases, n = 23). HPA-1a negative mothers were excluded. Control groups were screened positive mothers of healthy neonates (controls, n = 33) and female blood donors (blood donors, n = 19). LABScreen single antigen HLA class I beads was used for antibody analysis. Clinical records were reviewed for cases. RESULTS: All groups had broad antibody reactivity. Cases had more antibodies with high SFI levels compared with the controls (SFI>9999; medians 26, 6 and 0; P < 0·05) and higher overall median HLA-ABC and HLA-B SFI (P < 0·05). Many of the antibodies were reactive with rare alleles. When reviewing the clinical records, several of the cases had other contributing factors to the thrombocytopenia. There was no correlation between foetal platelet count and antibody levels. CONCLUSION: Mothers of thrombocytopenic neonates had higher levels of HLA class I antibodies compared with control groups of women with healthy children and female blood donors. However, clinical outcome and antibody response correlated poorly in the heterogeneous case group, indicating a multifactorial cause to the thrombocytopenia in the majority of cases.
Asunto(s)
Autoanticuerpos/sangre , Transfusión Fetomaterna/sangre , Antígenos de Histocompatibilidad Clase I , Trombocitopenia Neonatal Aloinmune/sangre , Femenino , Transfusión Fetomaterna/complicaciones , Humanos , Recién Nacido , Masculino , Embarazo , Trombocitopenia Neonatal Aloinmune/etiologíaRESUMEN
We have previously shown that tricyclic antidepressants can induce vaso- and bronchoconstriction as well as oedema formation in isolated perfused lungs. This is an effect similar to that seen clinically in adult respiratory distress syndrome. In order to investigate whether endothelin can be a mediator of this reaction, isolated perfused rat lungs were exposed to 0.1 mM amitriptyline via the pulmonary circulation, perfusate was collected and endothelin-1 present in the perfusate and lavage fluids was determined by radioimmunoassay. A significant increase in perfusate concentration of endothelin-1 was noted, with the highest release seen within the first 10 min. of exposure. Histamine and thromboxane have also been proposed as mediators in induction of adult respiratory distress syndrome. However, no increased amounts of these mediators were detected in the perfusate. Experiments where lungs were exposed to exogenous endothelin-1(0.1-1 nmol), both via the perfusate and via intratracheal instillation were conducted. Similar effects as observed with amitriptyline (0.1 mM) on lung function and perfusion flow were detected. In conclusion, the detection of endothelin-1 release in our lung model proposes a role for endothelin-1 in amitriptyline-induced vaso- and bronchoconstriction and possibly in adult respiratory distress syndrome type reaction. Further studies with this model are interesting in order to elucidate mechanisms behind the complex issue of adult respiratory distress syndrome-induction.