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Summary. The development of inhibitors is a compli-cation of replacement treatment in Haemophilia. Lossof factor VIII-specific memory B cells in the spleen isassociated with down regulation of antibodies in micetreated with high doses of FVIII, but changes in B cellmemory have not been described in haemophilicpatients. The aim of this study was to evaluate thephenotype of circulating lymphocytes in severe haemo-philia A. Twenty patients with inhibitors (PI), 22without inhibitors (P), nine patients during immunetolerance induction (ITI) treatment and 20 healthydonors (HD) were included. Peripheral blood lympho-cytes were examined using flow cytometry. Anti-FVIIIantibodies were measured using Bethesda and flowcytometry. Percentages of T subsets and B lymphocyteswere similar in all groups. In contrast, memory B cells(CD27+) were decreased in PI and P compared withHD, but the level of significance was higher in PI(P = 0.001) than P (P = 0.01). PI with high level ofanti-FVIII antibodies presented the lowest B memoryvalues. CD70 expression was also lowest in PI. Non-switched CD27+ subpopulation (IgD+) was prevalentin PI, but did not show statistical significance. WhenITI failed, the percentages of CD27+ B cells after12 months of ITI were lowest. In a longitudinal studyperformed in four patients, an increased percentage ofCD27+ and CD70+ B cells during ITI was found. Thiswork suggests that different peripheral lymphocytemarkers, such as CD27 and CD70 on B cells, may behelpful to evaluate anti-FVIII response and to monitorthe success of ITI.Keywords: anti-FVIII antibodies, haemophilia, memory Bcells |
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