Bone marrow donor registries: the relation between registry size and probability of finding complete and partial matches [see comments]

In a registry of volunteer bone marrow donors, the relation between registry size and probability of finding an exact or partial match for a random recipient cannot be theoretically derived because it depends on specifics of the human leukocyte antigen (HLA) haplotype frequencies in the donor and recipient populations. The relation must be explicitly calculated using empirically determined HLA haplotype frequency data for all possible pairings between a donor and a recipient population. This report describes a general solution to this problem. The method shows that the relation of the probability of matching to registry size is sigmoidal, with small increases in probability at the extremes of registry size and a middle range of registry size within which the probability of matching increases most sharply. This range determines the approximate size of the most cost-effective registry. In addition, for any pairing of donor and recipient populations, there is a maximum probability of identifying a match of a given quality for a random recipient, which cannot be exceeded even if registry size were infinite. This upper limit is a function of the frequency of blank (or unknown) alleles in the donor and recipient populations; the higher that frequency, the lower the maximum probability of achieving any given quality of match. The determinants of the probability of achieving a given quality of match with a given registry size are (1) the genetic heterogeneity within the recipient and donor populations, which increases the registry size required to achieve a given probability of matching, and (2) the degree of genetic homology between the donor and recipient populations, which increases the maximum probability of matching and also lowers registry size requirements. The method described here can be used to estimate donor pool size requirements using any donor and recipient populations for which HLA frequency data are available.     

Interleukin-10 and Transforming Growth Factor-β in Early and Late Lesions of Patients with Leishmania major induced Cutaneous Leishmaniasis

Background

Cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. Better understanding of host immune response to the parasite leads to helpful strategies for disease control. Interleukin (IL)-10 and transforming growth factor (TGF)-β are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. However, there is little information about the function of IL-10 and TGF-β in old world cutaneous leismaniasis. The aim of this study was to analyze the role of IL-10 and TGF-β in human cutaneous leishmaniasis due to Leishmania major infection.

Methods

Biopsies were obtained from lesions of twenty proven cases of L. major induced cutaneous leishmaniasis. IL-10 and TGF-β positive cells were detected by immunofluorescence staining of frozen sections and compared between two groups of patients with early and late lesions.

Results

The mean percentage of IL-10 positive cells were significantly (P= 0.035) higher in late lesions (0.51±0.24) than early ones (0.15±0.07). Similar results were obtained for TGF-β with mean percentages of 0.16±0.05 and 0.53±0.28 in early and late lesions respectively (P= 0.008).

Conclusion

IL-10 and TGF-β are present in lesions of L. major induced cutaneous leishmaniasis and contribute to the pathogenesis of long lasting disease forms.     

Screening with monoclonal anti-Fy3 to provide blood for phenotype- matched transfusions for patients with sickle cell disease

BACKGROUND: In the United States, there is a shortage of blood group phenotype-matched red cells (RBCs) for patients with sickle cell disease (SCD). A protocol designed to supply phenotype-matched RBCs for these patients by combining the recruitment of African American blood donors and automated testing of RBCs for these patients for the presumptive Fy(a-b-) phenotype using monoclonal anti-Fy3 was evaluated. STUDY DESIGN AND METHODS: African American donors were recruited, to increase the likelihood of phenotype matches in the donor population. Samples of RBCs were tested for the presumptive Fy(a-b-) phenotype by using monoclonal anti-Fy3 and an automated blood typing analyzer. RBCs confirmed to be Fy(a-b-) were retyped for selected Rh, MNS, Kell, Duffy, and Kidd blood system antigens. The extended phenotypes were matched with those of 41 SCD patients requiring transfusions. RESULTS: Of 8323 blood donations during the study, approximately 40 percent (3329) were made by African Americans. Approximately 22 percent (737) of African Americans were identified as Fy(a-b-) by this protocol and 12 percent (410) were phenotype matches for the 41 SCD patients. CONCLUSION: Combining the recruitment of African American blood donors and automated phenotyping using monoclonal anti-Fy3 offers a practical, relatively low-cost strategy for supplying phenotype-matched RBCs for SCD patients. This protocol increases the options for addressing the shortage of phenotype-matched RBCs for SCD patients.