HLA and non HLA antibodies in organ Transplantation
J. Martorell. Servei Immunologia H. Clínic, IDIBAPS

Session Start: Mon Mar 13 22:00:12 2000

[22:00] -uni- Welcome - Welcome to the First Congress of Nephrology in Internet http://www.uninet.edu/cin2000 Online discussions will be held at 22 hours GMT +1. Bienvenidos al Primer Congreso de Nefrología por Internet. http://www.uninet.edu/cin2000 Las discusiones on-line comienzan a partir de las 22 hora #cin2000
[22:05] (perico) buenas noches, vamos poco a poco
[22:05] (MJesus) Mai Ots, from Stonia, welcome
[22:05] (maio) Hello
[22:05] (Martorell) Buenas noches
[22:05] (MJesus) Martorell, bona nit
[22:06] (MJesus) perico buenas noches
[22:10] (MJesus) buenas gtorres
[22:11] *** Abboud (jirc@ has joined #cin2000
[22:12] (MJesus) abboud, welcome
[22:12] (MJesus) I intriduce Dr. Addoud, fron Qatar
[22:13] (Abboud) Hello Maria and other colleagues
[22:13] (MJesus) how are you Omar ?
[22:13] (Abboud) I am fine
[22:13] (gtorres) hello dr.Abboud
[22:14] (Abboud) Hello gtorres
[22:16] (MJesus) Abboud, what about the Marocco Congress ?
[22:16] (Abboud) it went well and was well attended by about 1000 delegates
[22:17] (MJesus) 1000 ??????????
[22:17] (Abboud) from the Middle East countries.... a
[22:17] (MJesus) 1000 nephrologist ??????????
[22:17] (gtorres) ist a pleasure to know about you
[22:17] (Abboud) and other cuntries from Southern Europe...
[22:18] (Abboud) I didn't meet any colleague from Spain..
[22:18] (miri) Buenas Tardes, M. Jesus
[22:18] (MJesus) miri, good afternoon...
[22:18] (MJesus) Miri is from Ecuador ?
[22:19] (gtorres) good afternon miri
[22:19] (miri) Si, soy de Quito
[22:20] (gtorres) we start just in a moment
[22:20] (miri) Buenas Tardes, g. Torres
[22:21] (MJesus) miri, MIF
[22:21] (MJesus) estamos con abboud, and Ots, que no hablan español
[22:21] (MIF) Hola, llegue
[22:21] (MJesus) MIF is marcos Iraola, from Cuba
[22:25] (perico) today, we will discuss Dr. Martorell´s conference
[22:25] (Speaker) HLA and non HLA antibodies in organ Transplantation
[22:25] (Speaker) J. Martorell. Servei Immunologia H. Clínic, IDIBAPS
[22:26] (Speaker) HLA antibodies
[22:26] (Speaker) Sensitizing elements:
[22:26] (Speaker) - Pregnancy 1/4
[22:26] (Speaker) - Blood transfusion 1/4
[22:26] (Speaker) - Previous transplant 3/4
[22:26] (Speaker) Broadness of Panel Reacting Antibodies (PRA), expressed in % of positive panel cells:
[22:26] (Speaker) - Indicates the percentage of donors that will give a positive Cross-Match.
[22:27] (Speaker) Specificity:
[22:27] (Speaker) - Indicates the HLA specificities that should be avoided in the donor to avoid a positive
[22:27] (Speaker) Cross-Match and a hyperacute rejection.
[22:27] (Speaker) - A receptor never has antibodies against its HLA specificities.
[22:27] (Speaker) - Antibodies to specificities that belong to the same CREG to the ones expressed
[22:28] (Speaker) in the receptor are infrequent.
[22:28] (Speaker) CREG (Cross Reacting Group):
[22:28] (Speaker) HLA specificities that share epitops
[22:28] (Speaker) - Epitop or antigenic determinant : Distinct sites to were an antibody can bind.
[22:28] (Speaker) - Is frequent to find receptors with antibodies against several HLA specificities that belong
[22:28] (Speaker) to the same CREG (A3-A11-A1; A2-A28; B5-35). (Slide 1)
[22:28] (Speaker) Title: Last positive of a serial dilution of a sera :
[22:28] (Speaker) Provides an approximate idea about the relative number of antibody molecules
[22:28] (Speaker) present per ml of sera or about its affinity for antigen.
[22:29] (Speaker) Antibodies removal:
[22:29] (Speaker) - Although low title antibodies can be removed by Protein A columns:
[22:29] (Speaker) - A rapid rebound of antibodies occurs in less than a week, usually in 24 hr.
[22:29] (Speaker) - High title antibodies can not be removed by Protein A columns.
[22:29] (Speaker) Isotype (IgG/IgM)
[22:29] (Speaker) - Aloantibodies are usually IgG but can be IgM.
[22:29] (Speaker) - Autoantibodies are usually IgM but can be IgG.
[22:29] (Speaker) - IgM can be inactivated by DTT (Dithiothreitol), that destroys -S-S- bonds
[22:29] (Speaker) Non HLA antibodies
[22:29] (Speaker) Non HLA antibodies
[22:30] (Speaker) Autoantibodies (to non polymorphic antigens)
[22:30] (Speaker) - Some patients present antibodies against non polymorphic antigens expressed
[22:30] (Speaker) on lymphocytes, and other cell membranes.
[22:30] (Speaker) - Autoantibodies are not harmful to the graft.
[22:30] (Speaker) - Are more frequent in patients with other autoimmune disease:
[22:30] (Speaker) -Systemic Lupus Erithematosus, -Primary Biliar Cirrhosis, -Rheumatoid Arthritis...
[22:30] (Speaker) - Can be detected by an auto-Cross-Match.
[22:30] (Speaker) - Does not react with the purified HLA antigens used as target when
[22:30] (Speaker) - ELISA and HLA coated beats FC are used for antibody screening.
[22:30] (Speaker) - Are usually IgM and in consequence inactivated by DTT.
[22:30] (Speaker) - Not all antibodies destroyed by DTT are autoantibodies.
[22:30] (Speaker) - Those reacting only with B cells could be anti-surface-IgG.
[22:31] (Speaker) Tissue specific antigens (Non HLA) . (Polymorphic or Non Polymorphic).
[22:31] (Speaker) In sera screening and crossmatching tests, the lymphocytes are used
[22:31] (Speaker) as representative target cells, because they have a good expression of the HLA antigens.
[22:31] (Speaker) In some rejections episodes, it has been described the presence, of antibodies
[22:31] (Speaker) reacting only with tissue specific antigens, expressed in endothelial cells and monocytes
[22:31] (Speaker) but not on lymphocytes membrane.
[22:31] (Speaker) - At least some of them had been proved to be against non polymorphic antigens.
[22:31] (Speaker) - Others seem to be polymorphic.
[22:31] (Speaker) - Those tissue specific antigens could be the reason for some rejections seen in patients
[22:31] (Speaker) with negative lymphocyte crossmatch.
[22:31] (Speaker) - Are more frequent in retransplant patients.
[22:32] (Speaker) - The prognostic value of those antibodies pretransplant is under discussion.
[22:32] (Speaker) In Organ Transplantation
[22:32] (Speaker) Crossmatch in kidney and pancreas Transplantation.
[22:32] (Speaker) Crossmatch is the test that detects the presence or not in the receptor of antibodies
[22:32] (Speaker) against the antigens of a particular receptor.
[22:32] (Speaker) A positive crossmatch had been considered an absolute contraindication for kidney
[22:32] (Speaker) transplant. Some special cases deserves some comments:
[22:32] (Speaker) Historic Positive, Current Negative:
[22:32] (Speaker) - The Cross-Match that is positive with historic sera but negative with the current sera
[22:32] (Speaker) had been considered a contraindication for transplantation since 1966 to 1980,
[22:33] (Speaker) on this year several papers reported a good survival in this kind of patients.
[22:33] (Speaker) - Today the issue is controversial and many centers consider that transplantation
[22:33] (Speaker) under this circumstances can have 1 year graft survival rate significantly lower than
[22:33] (Speaker) in the historic negative current negative cases (20 % less in our experience).
[22:33] (Speaker) T cell negative, B cell positive:
[22:33] (Speaker) - Many center had described that graft survival in case of T cell negative,
[22:33] (Speaker) B cell positive crossmatch is identical to the found in the T and B negative crossmatch.
[22:33] (Speaker) - Others by the contrary have found the presence of anti HLA-class-II antibodies
[22:33] (Speaker) reacting only with B cells in rejected kidneys. For some authors anti-HLA-class-II
[22:34] (Speaker) thats is all!
[22:35] (Martorell) Any question or coment?
[22:35] (MJesus) very godd, Dr. Martorell!
[22:36] (MJesus) congratulations
[22:36] (perico) do you think is worthwile studing patients with two or more organ loses in the way you have exposed ?
[22:37] (Martorell) Well it has been decribed that retraspalnted patients
[22:37] (Martorell) benefits from a FACS crooss-match
[22:38] (Martorell) BUt the problem is that theis thechnique has about 62 % false positives
[22:39] (MJesus) this is too much false positives !!!
[22:39] (Martorell) It means that CDC Neg FACS Positive in 62% of cases present no hipeacute rejection but
[22:39] (MJesus) it is not ??
[22:39] (Martorell) a good survival a year later
[22:39] (Martorell) Yes that is wath we think
[22:39] (MJesusr) whit this number.... no one pathologist was alive!
[22:40] (Martorell) by these reason we use only FACS cross-Match for living donation
[22:40] (perico) can you explain us what is a Facs croos-match?, because we are clinical nephrologists
[22:41] (Martorell) FACS means Fluorescent Activated cell Sorte
[22:41] (SCigarran) So, if i don´t missunderstood grafts with cross-match positive have done with some problems. So, What is the inmunoadsortion role?
[22:41] (perico) thanks
[22:42] (Martorell) and detects the human immunoglobulis attached to the donor cell by using an anti-humna IgG matket wioth FITC
[22:42] (Martorell) In oru experience the role for immunoabsotion is very limited
[22:43] (Martorell) by one reason is title of antibodies is over+
[22:43] (Martorell) over 1/64 the posibility to remove the antibodies
[22:44] (Martorell) is very poor because they rebound rapidly even if you use ciclofosfamide and so
[22:45] (Martorell) If title is un 1/64 the PRA almost never arrive to 90% it means you can found a negative
[22:45] (perico) Do you explain us how SLE antibodies can take part in the episodies of rejection
[22:45] (perico) ?
[22:46] (Martorell) Cross-Match of every 10 donors and in this cases Immunoadsobtion is not ncessary
[22:47] (Martorell) No SLE antibodies are autoa natibodies that react with non polimorfic determinants nomaly had no role in rejection
[22:49] (MJesus) monty, re-welcome
[22:50] (gtorres) are there any question?
[22:50] (gtorres) dr. perico?
[22:51] (perico) it is a very dificult theme for us
[22:51] (perico) We are grateful to Dr. Martorell for his technical explanations
[22:52] (Martorell) You are welcome
[22:52] (SCigarran) Thanks a lot Dr Martorell
[22:52] (perico) is there any other conferenciant in the Channel?
[22:54] (perico) We hope that Dr Martorell could understand our limitations in this theme
[22:54] (Martorell) Don worry i dont now almost nothing about nefrology
[22:55] (Martorell) but I think that is a good to transmit some concents abot crossmatching
[22:55] (perico) but, in spite we have read the conference previously, we can not to explote all Dr, Martorell know about this
[22:56] (Martorell) because could help you to found an apropiated donor for your patients
[22:57] (perico) creo que podemos hablar ahora en castellano, nos entendermos mejor
[23:03] (SCigarran) well, good night to everybody. Thanks a lot. See you tomorrow
[23:03] (MJesus) see you secundino
[23:04] (SCigarran) Bye
[23:04] (perico) buena noches
[23:04] (SCigarran) Bueno, Hasta mañana a todos. Buenas Noches. Nos vemos mañana

Session Closed: Mar 13 23:04:36 2000