Ágnes Padányi

Alloimmune and autoimmune background in recurrent pregnancy loss - successful immunotherapy by intravenous immunoglobulin.

Immunotherapies [leukocyte immunization, intravenous immunoglobulin (IVIG)] introduced to treat women with recurrent spontaneous abortions (RSA) have still controversial results in most clinical trials. A selection of these patients would be advantageous for higher efficacy.

The polymorphic human TLX-B/CD46/MCP system and its implications in transplantation and reproduction

TLX antigens have been found on most peripheral blood cells, trophoblasts, seminal vesicle cells and sperms. These antigens seem to be associated with the membrane co‐factor protein (MCP) and the CD46 antigen. Alloantibodies to TLX antigens with FctRII‐blocking features were obtained by transfusion of leucocytes or platelets. Preliminary population studies revealed that alloantibodies to TLX/CD46/MCP recognize four overlapping specificities. The terminology TLX‐B was introduced with specificities TLX‐BI, B2, B3, B4 and frequencies obtained in the population were: 38%, 46%, 42% and 26%, respectively. Family studies showed an independent segregation of the TLX and HLA alleles.

Long-term related kidney graft survival in high-risk patients after monitored donor-specific transfusion protocol

Abstract Altogether 57 patients were included in the related kidney transplantation program. Forty‐four recipients were mixed lymphocyte culture (MLC) negative or slightly positive (SI < 7) against their mother/father donor, and most of them showed Fey RII [erythrocyte antibody inhibition (EAI)] blocking antibody in their sera as the consequence of previous random transfusion. Thirteen patients showed significantly high MLC reactivity against their prospective parent donor (SI < 7) and had no EAI blocking antibody in their sera. The latter group was immunized either by buffy coat or purified platelets obtained from their donor in general two or three times at biweekly intervals. The indication for transplantation of donor‐specific transfusion (DST)‐treated patients was based on the appearance of EAI antibody and a significant reduction in the MLC reactivity (9 patients). DST patients had 100% kidney graft survival for 5 years and the DST untreated ones 75 %. Suggested responsible factors for this observation are the haploidentity in HLA and the induction of suppressive immune regulation by DST.

Temporary Tolerance or Suppressive Regulation Induced By Non MHC Alloantigens in Transplantation and Pregnancy

A special type of tolerance or suppressive regulation will be reported, which can be characterized by the complementary participation of two alloantigen systems; the major histocompatibility complex, and either a minor histocompatibility or certain type of differentiation antigen (secondary, subordinated) alloantigen system of functional importance. There are representative experimental observations on this phenomena, from which one characteristic model, reported by Hutchinson and Morris (Hutchinson and Morris 1987) is explained. Prior to kidney transplantation between RTL incompatible rats recipients were transfused with blood obtained from various strains characterized by either matching or mismatching with the transfusion and organ donor or recipient strain in the minor histocompatibility system. The matching between transfusion and kidney donor and a mismatching between transfusion donor and organ recipient as regards minor histocompatibility alloantigen system has to be emphasized as a new requirement. No similar situation has been reported in human beings. However, the induction of tolerance by transfusion in certain models is a well established phenomena. The importance of class II antigen matching between transfusion donor and recipient were outlined and proved in series of clinical observations based on in vivo and in vitro parameters including cytotoxic antibody production, MLC, cytotoxic precursor cell function and kidney survival (Lagaay et al. 1989, Claas et al 1991, van Rood and Claas 1990, de Waal and van Twuyer 1991).

Familial multiple myeloma. Two more families

The authors report on two multiple myeloma sibling pairs. In the absence of a known disease-specific marker one can only speculate on an explanation: is it because of inherited errors or is it related to the same environmental exposure, or both? In this study HLA typing and metabolizing enzyme polymorphism studies have been carried out with the aim of finding inherited similarities in the siblings or characteristics that might differ from the average population. Sibling pair 1 shared an HLA haplotype. Sibling pair 2 shared only HLA-B51, DR4, DRw53, DQ3. Sibling 1/1 was GSTT1 / GSTM1 null and GSTP1 Ile105Val; sibling 1/2 was a GSTT1 / GSTM1 heterozygote and GSTP1 Ile105Val; sibling 2/1 and 2/2 were GSTT1 heterozygotes and shared GSTM1 null / GSTP1 Ile105Ile. The siblings had identical light chain or heavy chain secretion, or both. The similarities found in the inherited factors together with the same environmental exposure in the siblings’ first 20 years of life imply that the development of the same disease cannot be a coincidence.

P733 - Association between long term kidney Graft survival and the presence of pre transplant cytotoxic anti-HLA and/or non-MHC “Fe-GAMMA-RII blocking” (ANTI-TLX) alloantibody

One hundred kidney graft recipients were analysed retrospectively with regard to the presence of Fc gamma RII (EAI) blocking or cytotoxic HLA antibody induced by pretransplant transfusion. Previous studies suggested that transfusion induces the production of EAI blocking antibody which may have specificity to TLX/CD46/MCP alloantigens. A superior graft survival (65%/9 yr) was found in the presence of EAI alloantibody compared to graft survival in the absence of this antibody (40%/9 yr). Further analysis showed the following survival rates in relation to the combined appearance of HLA cytotoxic and EAI antibody (EAI positive, HLA negative 67%/9 yr; EAI positive, HLA positive 60%/9 yr; EAI negative, HLA positive 0%/9 yr; EAI negative, HLA negative 40%/9 yr). There was striking low graft failure in the first 6 months in patients with EAI antibody. Taking into consideration that the HLA B/DR mismatching grade in all various groups were the same and no considerable difference was found in association to graft survival, the presence or absence of alpha EAI (anti-TLX) antibody solely seems to have superior or additional effect on graft survival as compared to HLA matching.