SERIAL ANALYSIS OF HLA SPECIFIC ANTIBODIES

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#66
SERIAL ANALYSIS OF HLA SPECIFIC ANTIBODIES – THEIR "NATURAL" HISTORY.
M. Hathaway PhD , A. Nye BSc , S. Singh BSc and D. C. Briggs, PhD . Birmingham United Kingdom, National Blood Service, B15 2SG, Histocompatibility & Immunogenetics .

HLA alloantibody production may be stimulated by via transfusion or transplantation. Donor specific antibodies are associated with graft rejection and can be cause or consequence of the process. Their presence at transplantation can cause hyperacute rejection of renal allografts. For some, antibody production persists following stimulation and the majority of potential donors are unsuitable due to positive crossmatch. Excluding restimulation via transfusion, why such persistence occurs remains speculative. In order to manage highly sensitised patients a full understanding of the principles underlying persistent sensitisation is essential. In an attempt to address this we determined both IgG/IgM PRA levels together with serial analysis of HLA antibody specificity over an extended period.
IgG /IgM PRA levels were determined via a dual staining flow cytometry technique. ELISA determined antibody specificity for HLA and class 1 and class 2. Serial analysis for class 1 specificity was determined using single antigen flowbeads.
HLA antibody persists in some patients for more than 10 years. Persistence is often but5 not always maintained by subsequent transfusion. IgM antibody levels can be transient although IgM antibody is also persistent in patients with persistent IgG antibody. Serial analysis shows that changes in specificity are not always mirrored by changes in PRA. These changes can be both dependent and independent of specificity. Serial analysis can distinguish between distinct specificity and cross-reactive groups.
HLA antibody production can be transient in some patients whilst persistent in others. This persistence can be the result of a repeat challenge via transfusion. Such persistence is not related to the ability to class switch from IgM to IgG since both IgG and IgM can persist.