OD-08. Prevalence of allele-specific anti-HLA-antibodies
Olga S. Starikova, Ekaterina G. Khamaganova, Mikhail Yu. Drokov, Igor Yu. Urybin, Vera A. Vasilieva, Ekaterina D. Mikhaltsova, Natalia N. Popova, Daria S. Dubnyak, Anna A. Dmitrova, Olga M. Koroleva, Natalia M. Nikiforova, Zoya V. Konova, Mobile I. Akhmedov, Maria V. Dovydenko, Ulyana V. Maslikova, Feruza A. Omarova, Elmira I. Kolgaeva, Anna S. Garmash, Larisa A. Kuzmina, Elena N. Parovichnikova,
National Medical Research Center of Hematology, Moscow, Russia
Mikhail Y.u Drokov, e-mail: email@example.com
Several studies demonstrate that anti-HLA antibodies can be detected in both patients and healthy donors. Risk factors for anti-HLA antibodies formation are primarily pregnancy and donor blood components transfusions. However, the mechanism remains the same and consists of exposure to foreign donor cells alleles. However, data on exposure frequency and immunogenicity of these alleles are not available. In our study we tried to assess based on indirect data the frequency of exposure to foreign HLA and their immunogenicity by evaluation of anti-HLA antibodies occurrence rate in patients with hemoblastosis and bone marrow donors. Purpose of our work was to evaluate the rates of anti-HLA antibodies occurrence directed against various alleles and their immunogenicity.
Materials and methods
We analyzed serum samples of 12 people, including 4 healthy donors and 8 patients with hematological diseases (5, acute leukemia; 1, MDS; 1, aplastic anemia; 1, primary myelofibrosis). The median age was 46.5 years (range 24 to 65). M/F ration was 1/10, and the donor group included only women with history of 2 or more pregnancies. Serum samples were taken from patients before conditioning regimen initiation and from donors prior to start of the stimulation. The presence of allele-specific anti-HLA antibodies in serum was tested by solid-phase immunoluminescence analysis on the LUMINEX platform. The assay is carried out on a 96-hole plate. The patient’s serum is added to the microspheres carrying antigens of different HLA loci on their surface. If serum contains antibodies, then an antigen-antibody complex is formed on the surface of microspheres. Then anti-human IgG connected with phycoerythrin is added and incubated. And then the fluorescence intensity is measured. “Positive” is the result of an average fluorescence intensity (MFI) of more than 750. Moreover, the higher the MFI, the greater the number of antibodies to a particular allele detected in a person.
The results are shown in Figures 1-5, where vertical axis indicate the particular HLA locus alleles, while horizontal one contains MFI values. The dots correspond to MFI values in the studied sera. The vertical lines in blue, yellow, and red serve as cutoffs for the MFI value. The high MFI values are more often detected for the most polymorphic HLA-B locus.
The high frequency of anti-HLA cells to certain alleles may be due to the higher occurrence of these alleles in the population, as well as their higher immunogenicity in comparison with others, or a combination of these conditions. This issue seems to us extremely interesting and requires further study in a larger cohort.
Anti-HLA antibodies, allo-HSCT.
Figure 1. MFI value for anti-HLA antibodies to various HLA-A alleles
Figure 2. MFI value for anti-HLA antibodies to various HLA-B alleles
Figure 3. MFI value for anti-HLA antibodies to various HLA-C alleles
Figure 4. MFI value for anti-HLA antibodies to various HLA-DQB1
Figure 5. MFI value for anti-HLA antibodies to various HLA-DRB1 alleles