Alloimmunity

Contamination of blood products with lymphocytes can lead to transfusion-induced reactions ranging from a mild fever to severe reactions such as alloimmunization and graft versus host disease (GvHD), in which the transfused lymphocytes (graft) survive the defensive immune reaction of the patient (host) and start a reaction which destroys the cells of the host. The patient also may develop an immune response to the human leukocyte antigen (HLA) type of the graft s cells and reject all platelet transfusions that do not match their own HLA system. The HLA system, found on blood platelets and lymphocytes, is more compHcated than, but similar to, the ABO blood group system of red cells. 

Combinations of centrifugation, countercurrent washing, filtration, and uv-irradiation are being investigated to avoid alloimmunization or GvHD. 

Filtration Filtration (qv) is appHed in blood cell separation to remove leukocytes from ted blood cell (RBC) and platelet concentrates. Centtifugational blood cell separators do not reduce white blood cells (WBC) in red cell and platelet products sufficiently to avoid clinical complications such as GvHD and alloimmunization. A post-apheresis filtration step is needed to further reduce the WBC load. Modem filters are capable of a 3-log reduction in white cell contamination of the blood product, eg, apheresis single-donor platelet units having a typical white cell contamination of 5 x 10 white cells in 4 x 10 platelets can be reduced to a 5 x 10 white cell contamination, a sufficiently low number to avoid severe transfusion reactions. 

Alloimmunity is the immune response mounted by a host on the basis of differences in major histocompatibility antigens expressed on the surface of a donor cell from the same species as the host. 

Sickle cell hemolytic transfusion reaction syndrome is a unique problem in SCD patients. Owing to alloimmunization, an acute or delayed transfusion reaction may occur. Delayed reactions typically occur 5 to 20 days after transfusion. Alloantibodies and autoantibodies resulting from previous... 

Chronic transfusion is indicated to prevent stroke and stroke recurrence in children. Transfusion frequency is usually every 3 to 4 weeks and should be adjusted to maintain HbS of less than 30% of total hemoglobin. The optimal duration is unknown. Risks include alloimmunization, hyperviscosity, viral transmission (requiring hepatitis A and B vaccination), volume and iron overload, and transfusion reactions. 

Previous studies on the effects of N=0 production on the alloimmune response utilized bulk populations of responder and stimulator cells. In order to more clearly define the circumstances that induce -N=0 synthesis in allogeneic macrophage-lymphocyte cocultures, mouse splenocyte populations were depleted of accessory cells (>90% Thy 1.2+) and cultured with mitomycin-C-treated macrophage cell lines, as the alloantigen presenting cells. The P388D1 (H2 ) and RAW 264.7 (H2 ) macrophage lines were selected because... 

MSCs offer several advantages for the treatment of GVHD and inflammatory and immune disorders. The ease of isolation, in vitro expansion, genetic stability, and ability to escape alloimmunity, make MSCs a model of choice for cellular therapy and also for gene... 

A recent report showed that the expression of IL-17 is closely related to the degree of the acute rejection of a renal allograft (L16). Therefore, IL-17 may be involved in the alloimmune response and serve as an early marker of acute rejection (L16). 

Petranyi GG (2002). The complexity of immune and alloimmune response. Transpl Immunol 10 91—100. 

It is now recognized that both active and passive factors of immune privileged sites contribute to their status. It has been know n for over 100 years that the AC of the eye possessed qualities allow ing a long-term survival of tissue and tumor grafts (van Dooremal, 1873). In the late 1970s Kaplan and Streilein discovered that antigenic cells placed into the AC w ere not only detected by the immune system, but also elicited a dow nregulation of alloimmune responses (Kaplan et al., 1975 Kaplan and Streilein, 1977). 

Finn OJ, Debruyne LA, Bishop DK (1996) T cell receptor (TCR) repertoire in alloimmune responses. Int Rev Immunol 13 187—207. 

PlPlAl-negative platelets are used to treat neonatal alloimmune thrombocytopenic purpura, a rare, transient, but severe thrombocytopenia in the newborn due to platelet destruction by maternal antibody (1). The mother is usually a PlPlAl-negative person who has produced anti-PIPIAI as a result of previous blood transfusions or pregnancy. The antibody crosses the placenta and destroys the PIPIAI-positive platelets of the neonate. 

Platelet concentrates contain a considerable number of leukocytes and it is not clear whether allo-antibody formation is caused by the platelets themselves or by these contaminating leukocytes (112). There is in fact evidence that leukocyte-free platelets could prevent refractoriness to platelet transfusion (113), and also that induction of anti-HLA antibodies is reduced (114). It has also been found that that the use of HLA-matched platelets almost entirely avoids alloimmunization (114). There was severe but transient thrombocytopenia after the infusion of whole blood from a donor who was subsequently found to have a high-titer platelet-specific antibody (anti-PlAl) (115) this, however, is very rare. 

Contreras M, Hazlehurst GR, Armitage SE. Development of auto-anti-Al antibodies following alloimmunization in an A2 recipient. Br J Haematol 1983 55(4) 657-63. 

Coles SM, Klein HG, Holland PV. Alloimmunization in two multitransfused patient populations. Transfusion 1981 21(4) 462-6. 

Two major classes of complications in the use of these proteins have emerged (1). First, transfusion-related infections with various blood-borne viruses, such as hepatitis B and C and human immunodeficiency virus (HIV). Secondly, alloimmune antibodies (inhibitors) against the deficient coagulation factors. 

Prevention of alloimmunization with leukoreduced blood products... 

Moise KJ Jr. Management of rhesus alloimmunization in pregnancy. Obstet Gynecol 2002 100 600-11. Review. Erratum in Obstet Gynecol 2002 100 833... 

Alloimmunization—Rapid consumption of transfused platelets via an immune mediated reaction. 

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