Hemoglobin A2 and Heterogeneous Diagnostic Relevance Observed in Eight New Variants of the Delta Globin Gene.

BACKGROUND: Hemoglobin A (Hb A) (α2ß2) in the normal adult subject constitutes 96-98% of hemoglobin, and Hb F is normally less than 1%, while for hemoglobin A2 (Hb A2) (α2δ2), the normal reference values are between 2.0 and 3.3%. It is important to evaluate the presence of possible delta gene mutations in a population at high risk for globin gene defects in order to correctly diagnose the ß-thalassemia carrier. METHODS: The most used methods for the quantification of Hb A2 are based on automated high performance liquid chromatography (HPLC) or capillary electrophoresis (CE). In particular Hb analyses were performed by HPLC on three dedicated devices. DNA analyses were performed according to local standard protocols. RESULTS: Here, we described eight new δ-globin gene variants discovered and characterized in some laboratories in Northern Italy in recent years. These new variants were added to the many already known Hb A2 variants that were found with an estimated frequency of about 1-2% during the screening tests in our laboratories. CONCLUSIONS: The knowledge recognition of the delta variant on Hb analysis and accurate molecular characterization is crucial to provide an accurate definitive thalassemia diagnosis, particularly in young subjects who would like to ask for a prenatal diagnosis or preimplantation genetic diagnosis.

Plasmapheresis therapy in pemphigus vulgaris and bullous pemphigoid.

Blistering dermatitises are characterized by the presence of blisters that begin owing to acantholysis (intraepidermic blister) such as pemphigus vulgaris (PV) or owing to dermoepidermic detachment (subepidermic blister) such as bullous pemphigoid (BP). Both diseases are autoimmune pathologies characterized by the presence of autoantibodies against specific adhesion molecules of the skin and mucous membranes. PV, in which oral lesions are always present, has a progressive course that, if the disease is not treated, nearly always brings to death from sepsis within a few years. In BP, oral lesions are rare and the disease, that is most frequent in older individuals, has a chronic course with spontaneous remissions. Systemic corticosteroids and immunosuppressants are the mainstay of treatment of these two diseases. Although this therapy had reduced the mortality of the two pathologies it is associated with serious side effects. To reduce the corticosteroids dose and to improve the symptomatology in resistant therapy cases, we treated five patients with several procedures of plasma exchange. Four patients were affected by BP and one by PV. Their disease severity at onset of plasmapheresis ranged from mild to severe. One of 5 patients suffered a plasmapheresis side effect. All patients responded with complete remission of symptomatology and had a prednisone dosage reduction until 70%. Plasmapheresis is an effective treatment for PV and BP patients who have been unresponsive to conventional therapy, for those for whom conventional drugs are contraindicated, for those who show severe clinical manifestations and for those who need high doses of corticosteroids and immunosuppressants to keep the disease under control.