Effect of splenectomy on type-1/type-2 cytokine gene expression in a patient with adult idiopathic thrombocytopenic purpura (ITP)

BACKGROUND: In view of clinical observations and laboratory results that support a central role of the spleen in idiopathic thrombocytopenic purpura (ITP) pathophysiology, we studied the effect of splenectomy on type-1 and type-2 cytokine gene expression in an adult ITP case, refractory to conservative treatment. CASE PRESENTATION: The patient was subjected to splenectomy 9 months after the diagnosis with complete response, attaining platelet counts over 150 × 10(6)/L within 10 days after the operation. Two consecutive blood samples were obtained from the patient, 3 and 7 months after the splenectomy for the purposes of this study. A control group consisted of 11 healthy adults. Peripheral blood mononuclear cells were prepared from each blood sample and cultured in vitro for 8 h with the addition of the mitogens phorbol myristate acetate and ionomycin. Total cellular RNA extracted from 10(6 )cells was submitted to semiquantitave reverse transcriptase-polymerase chain reaction (RT-PCR) for the amplification of IL-2, IFN-γ, IL-4, IL-5, and IL-10 metagraphs. The PCR products were run on ethidium-stained agarose gels, photographed and quantified by densitometry. A steep decrease of type-1 cytokine expression (IL-2, IFN-γ) and their calculated sum expressing Th1 activity was observed at 7 months post-splenectomy compared to 3 months post-splenectomy, in parallel with a rise of platelet count from 190 × 10(6)/L to 265 × 10(6)/L. The change of type-2 cytokine expression (IL-4, IL-5, IL-10) was slight and the Th2 activity (IL-4+IL-5) remained largely unchanged. The Th1/Th2 ratio, that reflects the pathogenic disease-specific T-cell immune deviation, was accordingly reduced 7 months post-splenectomy (Th1/Th2 = 1.3) compared to 3 months (Th1/Th2 = 3.5). CONCLUSIONS: The reduction of the Th1/Th2 cytokine ratio that was observed over time after splenectomy was accompanied by full clinical remission. Nevertheless, the persistence of a type-1 polarization, even after several months following spleen removal, is suggestive of a more basic abnormality of the immune function in these patients

Tailored versus standard dose prophylaxis in children with hemophilia A.

Prophylaxis is universally recognized as the treatment of choice in people with hemophilia, and tailored prophylaxis is the consistent modification of the standard weight-based dosing regimen. A large number of factors guide the choice of a specific tailored regimen, and different regimens are under evaluation. Tailored low-dose frequent regimens are likely to be cost-effective, but they are less accepted by patients. Escalating dose regimens seem to be quite effective in preventing bleedings and, consequently, arthropathy, although data on long-term outcomes are still not available. Pharmacokinetic-driven approaches have been also proposed. Sensitive and validated tools able to reliably measure the different outcomes are necessary in this setting. With regard to the evaluation of arthropathy, magnetic resonance imaging and ultrasound are promising imaging techniques in detecting early joint damage. Factor VIII trough levels can be considered a measure of the efficacy of FVIII infused, although other factors influence the bleeding pattern. Global assays of coagulation could provide more complete information on the hemostatic potential of a sample and predict bleeding phenotype. These techniques are also promising for the individualization of prophylaxis regimens, potentially resulting in less frequent dosing, more comfortable and less expensive approaches