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In the previous study we demonstrated that circulating levels of TNF-alpha are elevated during liver allograft rejection and may precede clinical manifestations. The current study was designed to investigate the efficacy of antibody therapy against tumor necrosis factor-alpha and lymphotoxin (LT) in a rat heterotropic cardiac transplant model utilizing Buffalo donors and Lewis recipients. Control animals received no immunotherapy and experienced rejection on postoperative day 11 +/- 0.4 (mean +/- SEM). Experimental animals received immunotherapy either intraperitoneal or intravenous from days 1 to 10. The i.p. administered anti-TNF-alpha prolonged graft survival to 16 +/- 2.7 days (P less than 0.05 vs. controls); the i.v. administration prolonged survival to 15 +/- 1.4 days (P less than 0.004). Animals treated with i.p. anti-LT survived 17 +/- 1.7 days (P less than 0.002 vs. controls). Combination immunotherapy of anti-TNF-alpha and anti-LT increased function to 21 +/- 2.2 days (P less than 0.001 vs controls). Conversely, administration of purified TNF-alpha or LT to graft recipients accelerated the time to rejection. Mean survival for both treatments was 7 days (P less than 0.001 vs. controls). Histologic examination of the transplanted cardiac tissue showed a typical pattern for acute rejection; there was no evidence of hemorrhagic or coagulative necrosis. In contrast, administration of purified TNF-alpha or LT to recipients of a syngeneic heart did not stimulate rejection. These data suggest that TNF-alpha and LT may play a role in the pathogenesis of acute allograft rejection. In addition, the mechanism appears to be distinct from that seen in TNF-alpha or LT-mediated cytotoxicity of tumor cells.

A. PATIENT SURVIVAL 1. The best cadaver graft patient survival 3-years posttransplant was observed in those whose primary disease was either nephrotic syndrome (98%), renal hypoplasia (98%), renal dysplasia (98%), IgA nephropathy (96%), or medullary cystic disease (97%). The worst survival was in those with Goodpasture's syndrome (88%), hypertensive nephrosclerosis (87%), MPGN (87%), IDDM (86%), and NIDDM (85%). 2. Patient survival correlated inversely with nonimmunologic graft loss. Nonimmunologic graft loss was high in patients with hypertensive nephrosclerosis (21%), polycystic kidney disease (23%), IDDM (27%), and NIDDM (27%). 3. Females with CGN and IDDM had better patient survival than males with the same diseases. The 2-, 3-, and 5-year survivals for females with IDDM were 91%, 89%, and 87% whereas for males, they were 87%, 84%, and 81%, respectively (p = 0.01). For CGN the 2-, 3-, and 5-year survivals were 95%, 94%, and 93% for females and 93%, 91%, and 90% for males (p less than 0.01). Females with Alport's syndrome had lower patient survival rates at 1 year (86%) than males (95%, p = 0.03). B. GRAFT SURVIVAL 1. The best 3-year graft survival was in recipients whose primary pathology was IgA nephropathy with 83% for cadaver grafts and 95% for LRD grafts. This was not secondary to center effects. The worst graft survival at 3 years for cadaver kidney recipients was in those whose primary illness was NIDDM (61%), hypertensive nephrosclerosis (58%), MPGN (59%), and Goodpasture's syndrome (59%).(ABSTRACT TRUNCATED AT 250 WORDS)

1. The 1-year graft survival rate for 3,525 Black recipients of first cadaver-donor transplants between 1985 and 1989 was 71%. For 13,866 Whites it was significantly higher at 78%, and 796 Asians had the highest 1-year graft survival rate at 83%. 2. When transplant centers were grouped according to the number of Black patients transplanted between 1985 and 1989, 1-year graft survival rates for Blacks ranged from 67% at centers that transplanted more than 100 Blacks to 74% at centers with 50-100 Blacks to 69% at centers with 1-50 Black transplants. The corresponding survival rates for Whites were 74%, 78%, and 78%, respectively (p less than 0.01 at each center group). 3. When the results were further stratified according to donor race and age, HLA-DR mismatches, and transfusions, a significant 6% difference remained between graft survival rates of Black and White recipients (p less than 0.01). 4. Similar stratified analyses for donor race yielded a significant 8% lower survival rate for Black donor kidneys compared to White donor kidneys (p less than 0.01). 5. More than 25% of Black recipients and donor kidneys were transplanted at 6 of the 204 centers reporting to the UCLA Transplant Registry, whereas 92 centers had transplanted no Black patients. 6. The main difference in survival between Whites and Blacks was among younger patients. There was a 13% difference for those younger than 30 (p less than 0.01), and only a 4% difference among patients older than 45 (p less than 0.05). 7. When HLA-DR antigens were matched, there was no difference in the survival rate between White and Black patients. This result was unaffected by the race of the donor, implying that racial HLA-DR variants may not be a major consideration in matching. 8. Black patients had poor long-term graft survival. The kidney half-life calculated after the first year for Black recipients was 3.7 years, and was 8.7 years for Whites (p less than 0.01). 9. There was a clear "center effect" component to racial differences in first cadaver kidney transplant outcomes related to the size of the Black recipient population. These center effects did not account for the overall difference between Black and White survival rates.

1. A yearly summary of the previous year's cells typed through the International Cell Exchange allows a participating laboratory to compare its own performance with 292 currently participating exchange laboratories, inasmuch as each laboratory receives its individual antigen report. We present an annual summary for the 1990 typings of 40 cells sent for Class I and 20 cells sent for Class II antigens. 2. The mean detection percentages and the detection ranges for 21 WHO-designated (well-defined) and 21 WHO-provisional (with "w" designations, less well-defined) antigens were determined for the Class I cells typed in 1990. Seventeen WHO antigens showed 95% or greater detection levels. The remaining WHO antigens showed at least 90% agreement, with the exception of B38. More variation in detection is observed in the WHO-provisional antigens. Aw33, Bw50, Bw60, and Bw62 showed 90% or greater average detection percents. In recent years, antigens such as Bw46 and Bw70, have shown great improvement in detection. 3. The percent discrepancy rates of 8 HLA-A,B antigens typed 4 times or more in 1990 were presented as well as the total percent discrepancy rates for all Class I antigens. Comparison of 1990 figures with those of 1988 and 1989 shows a marked decrease in the total discrepancy rates. 4. The number of false negatives and false positives for the Class I antigens indicates that few laboratories have trouble typing the WHO antigens; as many as 115 laboratories had 0 misses. However, a greater number of laboratories missed the less well-defined WHO-provisional antigens: 7 laboratories had 0 misses for all the antigens and 4 laboratories had perfect records (0 false negatives and false positives) for cells typed in 1990. 5. In 1990, the cell exchange continued to study new cell variants. An A10 (A26x34) variant was detected in 4 cells and another possible variant, B7x40 (DT), was determined in 3 cells. 6. The average detection percentages and detection ranges were determined for 23 Class II antigens. Improved detection is indicated. At least 9 Class II antigens showed 90% or greater agreement level, of which at least 4 had 95% or greater mean detection. 7. Since the incorporation of DNA typing results in the B-cell line exchange reports in July 1990, the Class II antigen splits in 11 cells have been confirmed or clarified. Two Class II variants were also confirmed by the DNA laboratories. Presently, 145 serology and 7 DNA laboratories are in this exchange.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Two-step Cox regression analyses showed that, for White recipients of first cadaver transplants, pretransplant transfusions, HLA-DR mismatch, donor race, CIT, size mismatch, PRA, old donor, and recipient age were significant prognostic factors during the first 6 months posttransplant, and after that, older donor, CIT, and size mismatch continued to have effects on graft survival in the longer term. 2. For African-American recipients of first cadaver transplants, pediatric donor, cause of donor death, and increasing second warm ischemia time were major risk factors in the early period, but in the late period, the effect of donor age dominated other factors. 3. Multistep linear logistic regression and two-step Cox regression analyses yielded similar results, with donor-related and histocompatibility factors dominating survival outcome in both the short and long terms.

1. Two-year 6-antigen-matched graft survival was 82% for first grafts and 72% for second grafts compared to 72% and 60% for the controls. 2. Six-antigen-matched transplants had longer mean ischemia times and recipients had higher levels of antibodies but the effect of these factors was insignificant compared to their effect on the controls. 3. One reason for transplant loss among the 6-antigen-matched recipients was inadequate transplant size. When kidneys from young or old donors were transplanted into heavy recipients, graft survival was 74% compared to 88% for median-age donors. 4. Six-antigen-matched transplants with common phenotypes (greater than 4 cases) had 2-year graft survival of 87% compared to 76% for those which occurred only once. 5. Difficulties in tissue typing certain antigens was shown to have an effect. Six-antigen-matched transplants with antigens defined by at least 80% of the tissue typing laboratories had 89% 1-year graft survival compared to 73% for those with antigens which were more difficult to define. 6. There were fewer homozygous donors and more regraft transplants than expected.

There is evidence that many of the so-called multispecific cytotoxic antisera react to the amino acid-defined epitopes of the HLA-A and B loci molecules. This evidence is based on the finding that a group of sera produced allelic reactions which corresponded to amino acid substitutions. Antisera for 29 amino acid variants were identified at 67 variable residues on the A locus and for 17 of the 51 variable sites on the B locus. The results were validated by showing that the reactions produced by testing cells from 111 individuals on an epitope typing tray fit the Hardy Weinberg equilibrium. This means that the alleles defined by the antisera behaved as alleles in the random population. Tests of homozygous cells on the epitope typing trays produced completely mutually exclusive reaction patterns as expected on the basis of the amino acid substitutions. Two examples are cited in which immunization across a single HLA "antigen" difference existed between donor and recipient, resulting in a "multispecific" antiserum. The specificities contained in the serum exactly fit an amino acid difference between the donor and recipient.

Based upon data reported to the UNOS Scientific Renal Transplant Registry between October 1987 and October 1990: 1. One-year graft survival rates were 78% for 14,203 recipients of first cadaver donor transplants, 70% for 2180 recipients of second cadaver transplants, and 59% for 487 recipients of third or fourth transplants. First transplants from living donors had 90% 1-year graft survival. 2. One-year graft survival was 75% for 2,273 Black recipients of first cadaver transplants and ranged between 79-80% for recipients of other races (p less than 0.001). 3. Broadly sensitized (50% peak PRA) first cadaver transplant recipients had 77% 1-year graft survival versus 79% for nonsensitized or narrowly sensitized recipients. Cadaver retransplant recipients with greater than 10% peak PRA had 65% 1-year graft survival while those transplanted with no antibody had 78% (p less than 0.001). Survival of nonsensitized retransplanted patients was not significantly less than first transplant recipients. 4. Graft survival was 78% at 1 year for both male and female recipients of first cadaver donor transplants. Retransplanted females had significantly higher 1-year graft survival at 70% than males at 67% (p less than 0.01). Male donor kidneys had significantly higher survival rates than female donor kidneys in both first and retransplanted patients. One-year graft survival was 79% and 70% with male donors and 75% and 65% with female donors in first and retransplants, respectively (p less than 0.01). 5. Pediatric recipients (under 16) and older recipients (over 60) of first cadaver transplants had 73% 1-year graft survival compared to 78-79% for those aged 16-60. 6. Among recipients of first cadaver transplants, 1-year graft survival rates varied over a 20% range with the age of the donor. Excluding pediatric and older patients, the best survival rates (81%) were obtained with kidneys from donors aged 16-45. Kidneys from younger and older donors yielded progressively poorer results. The lowest survival was with 181 donors aged 1-5 (60%) and 145 donors over 60 (69%). 7. One-year graft survival was 85% for 274 recipients of 0 HLA-A,B,DR-mismatched first cadaver transplants and 74% for 717 recipients of transplants mismatched for 6 HLA-A,B,DR antigens. Graft survival progressively declined with increasing histoincompatibility. 8. One-year graft survival decreased by 20% if the kidney failed to produce urine in the first hour, from 80-60% in first transplant recipients and from 72-50% in retransplanted patients.(ABSTRACT TRUNCATED AT 400 WORDS)

1. Greater than 50% PRA-sensitized first kidney graft recipients show significantly lower graft survival rates than nonsensitized (0-10% PRA) and moderately sensitized (11-50% PRA) recipients. Most of the effect of sensitization can be seen within the first month posttransplantation. 2. Increases in cellular immunity or antibodies not currently detected by lymphocyte cytotoxicity may account for the decreased graft survival rates in second and multiple graft recipients. One possibility involves the presence of antiplatelet antibodies. 3. Transfusions seem to be the weakest stimulus for sensitization when compared to pregnancy, and to graft failure, which is the strongest. In addition, low numbers of transfusions tend to have a beneficial effect, especially on second kidney graft survival. 4. During the years since the prospective use of the T-cell FCXM by Los Angeles transplant centers, there has been a marked increase in graft survival rates for multiple graft recipients. However, the rates for the sensitized multiple transplant group still remain lower than those for the nonsensitized first and multiple graft groups.

Sera from normal humans were cytotoxic to autologous and allogeneic epidermal cells. Sera from newborns were not cytotoxic, which is consistent with earlier results suggesting the gradual development of autoantibodies in animals. With anti-human IgG fluorescein-labeled conjugate staining, it was shown that the outer layers of the epidermis were stained by the natural autoantibody. No staining, however, was noted with sera from newborn cord blood. Another autoantibody induced by burns associated with autograft rejection was found to stain specifically the cells of the basal layer of the epidermis. The basal layer cells were not stained by HL-A antibodies. It is concluded that autoantibodies to the outer layers of the human epidermis occur naturally, and autoantibodies to the basal layer can be induced by burn injury associated with autograft rejection.

Two cytotoxic monoclonal antibodies (D5D6 and C10H5) were raised to acute myelogenous leukemia (AML) cells. One of them, D5D6, reacted with 100% of the cells from 44/50 AML patients. The second, C10H5, reacted with 100% of the cells from 13/39 AML patients. D5D6 and C10H5 were cytotoxic to 100% of the monocytes from all healthy donors tested. Apart from monocytes, these antibodies did not react with any other peripheral blood cells from normal donors or with cancerous cells either from cell culture lines or from patients with chronic myelogenous leukemia (CML), lymphoid leukemias, or solid tumors. These antibodies inhibited the growth of the myeloid-monocytic stem cell, the CFU-C, and reacted with a minor population of normal bone marrow cells by immunofluorescence. Both D5D6 and CH5 have potential utility for the differential diagnosis of acute leukemia, for the detection of early leukemic relapse, and for enrichment of human stem cells.

Homozygous DW typing cells were tested for six B-lymphocyte specificities. All four of the second locus specificities of B lymphocytes were strongly associated with the DW specificities. DW1 typing cells were B group 6, DW2 were B4, DW3 were B5, and LD107 were B3. The first B-cell locus antigens 1 and 2 tended to be uniform within the DW groups. From an analysis of the typing responses of a panel of cells to the homozygous typing cells, it has become apparent that the first B-locus specificity present on the homozygous typing cells also plays a role in determining whether a typing response is obtained or not. Thus, the DW3 typing cells were themselves B2 and B5, and cells having B2-B5 were most frequently nonreactive to DW3 in mixed lymphocyte culture. Homozygous typing cells therefore mainly detect the second B-cell locus antigens and, to a lesser degree, the first locus specificities. Stated another way, homozygous typing cells do not define a single specificity, but rather the presence of two B-lymphocyte specificities, even though their responses often reflect matching of only the second B-locus specificity.

The serologic activity of soluble human histocompatibility (HL-A) antigens extracted from four human cultured lymphoid cell lines by the 3M KCI method has been evaluated by their ability to inhibit...

Tolerance of skin homografts was studied after the injection of various adult cells and soluble tissue extracts into newly hatched or embryonic chicks. Tolerance (measured by the proportion of surviving skin homografts 30 days after transplantation) was induced in 50 per cent, or more of the chicks injected with diluted whole blood, blood lymphocytes, blood monocytes, and thymocytes. Since monocytes and thymocytes do not produce a ‘graft against host’ reaction it follows that tolerance to homografts can be induced by adult cells without the complications associated with runt disease. Tolerance could not be induced with cell-free extracts of known antigenic potency. Analysis by the tolerance test of the appearance of adult-type iso-antigens during embryonic development shows that they are detectable by the 4th day of embryonic life.

In recent years extensive investigations have been directed toward determining the biologic and chemical profiles of soluble HL-A alloantigens isolated from a variety of tissue sources. During the course of such studies, the in vitro reactivity of these materials was established serologically by their ability to inhibit specifically cytotoxic alloantisera (1). The soluble HL-A antigens have been shown to have further immunologic significance as they can induce specifically blastic transformation of histoincompatible but not of isogeneic leukocytes in vitro (2). Chemical studies thus far suggest that HL-A antigens are essentially protein in nature and apparently consist of single polypeptide chains with a molecular weight of 31,000 (3). The data concerning the immunogenic properties of soluble HL-A alloantigens thus far are scanty and conflicting. Batchelor (4) reported that rabbits immunized with partially purified soluble HL-A substances produced only species-specific lymphocytotoxic antibodies.

An attempt has been made to identify the cell responsible for the splenic enlargement caused by the injection of adult homologous blood and spleen cell suspensions into embryonic or newborn chicks. Adult chicken blood lymphocytes 99–100 per cent, pure produced marked splenic enlargement when injected intravenously into chick embryos of a different breed or strain. As little as 30,000 lymphocytes could produce a detectable effect. Adult chicken spleen-cells also produced enlargement of the embryonic spleen. Adult monocytes and thymocytes did not cause significant enlargement. Evidence is presented that the development of inflammatory nodules after the local intracutaneous injection of cells from adult homologous donors is, like splenic enlargement, principally the result of a reaction of the grafted cells against the host. Adult blood lymphocytes when injected intracutaneously were shown to cause the production of a nodule in 3–5 days. Monocytes and thymocytes did not cause the formation of these nodules. From these experiments it is concluded that, in chickens, cells of the peripheral blood lymphocyte family are immunologically competent, and are capable of producing an iso-immune reaction against antigens present in their embryonic or juvenile host.

Thirty-three of 34 cultured human lymphoblastoid B cell lines have been shown to express four out of five polymorphic non-HLA specificities expressed by normal B lymphocytes. The specificities were detected by 32 alloantisera produced by absorption with pooled platelets to remove HLA activity and selected from over 400 pregnancy sera. One B group (B2) which was expressed by 23% of a panel of normal B lymphocytes was not found on any of the cultured lines tested. Four T cell lines tested and myeloid line (K562) did not react with any of the B cell alloantisera.

The variable expression of the C locus specificities at the cell surface is a major problem in HLA typing and the phenomenon was clearly documented by the International Cell Exchange Program. In contrast with HLA-A and -B, the C locus specificities are readily lost from cells following storage at room temperature for a few days or in overnight incubation at 37 degrees C in the presence of protein synthesis inhibitors. These specificities can be made to reappear by making the cells metabolize at 37 degrees C for 8 to 20 h in nutrient medium. Sixty-nine per cent of the positive C locus reactions lost after 7-day storage at room temperature were recovered after overnight incubation at 37 degrees C. The reappearance was dependent on protein synthesis since presence of cyclohexamide during incubation completely blocked the recovery. A simple overnight incubation is very useful in enhancing C locus expression on older cells.

We tested HLA-DR antigens in 38 Caucasian, 18 Negro, 17 Mexican, and 5 Japanese patients with rheumatoid arthritis. Significantly high HLA-DR4 frequencies were observed in all races; 61% in Caucasians, 39% in Negroes, 77% in Mexicans, and 100% in Japanese. However, no clinical correlation with DR4 was found in these patients.

In order to compare the efficacy of simple hypothermic preservation of cadaver kidneys in Collins solution with preservation by pulsatile perfusion, data were gathered on over 1000 transplants between December 1973 and June 1975. In this series of new patient data, it was found that the 1-year thansplant survival rate of 59%+5% in 89 kidneys preserved in Collins solution was significantly better than the 41% + 3% rate found with 358 kidneys preserved by the Belzer machine (p = 0.005). This survival rate was better than the 47% + 3% rate in 421 kidneys preserved on the Waters machine (p = 0.05), and the 34% + 6% rate of 97 kidneys preserved by cold storage in Sacks solution (p = 0.005). The difference in centers probably did not influence the data, since 28 centers submitted data on the Collins-preserved kidneys. In addition, 43 of the 89 kidneys. In addition, 43 of the 89 kidneys stored in Collins solution had been shared between centers.

Fifty cadaveric kidney donors were randomly allocated to two groups. Group 1 received 5 grams of intravenously administered methylprednisolone two to four hours prior to organ harvesting after the pronouncement of brain death. Group 2, which served as the control group, received no pretreatment. Of 100 kidneys harvested, 16 were discarded for various reasons, and 84 were transplanted and were available for evaluation, 40 from the pretreatment group and 44 from the control group. The transplant centers using these kidneys were unaware of the status of the kidney they received, that is, whether it was from a pretreated or a control group. The two groups of kidneys, pretreated and control, did not differ according to the length of warm or cold ischemia time or presence of preformed cytotoxic antibodies. The difference in graft failure between the two groups at three months was insignificant, even when the two groups were compared according to the method of preservation used.

We have found the ABO barrier does appear to remain intact in clinical kidney transplantation, as evidenced by a 4% 1-year graft survival in 25 cadaver donor, ABO-incompatible allografts. The one long-term surviving graft could have been a case of an A2 kidney and a B recipient, but this could not be determined. Although these grafts were the result of errors at a number of different points, most could have been avoided if a red cell crossmatch had been performed at the time of transplant. The fact that these transplants rarely occur should not overshadow the possibility that they could be avoided by the implementation of such a simple procedure.

We reviewed 14,005 renal grafts with the temporal opportunity for 10-year survival (transplanted 1975 and earlier) and analyzed 10-year actuarial graft survival and the rate of late (3- through 10-year) graft loss as reflected by half-life. The 10-year graft survival for first transplants in HLA-identical siblings was 67% versus 38% for parental donors and 20% for cadaver donors. Factors with substantial influence on 10-year graft survival include transplant number, transfusions (0, 17%; greater than or equal to 1,33%), HLA-A,B mismatches (0, 29%; 1-2, 20%, 3-4, 17%), cold ischemia time (0-3 hours, 32%; 4-6 hours, 27%; 7-12 hours, 21%; greater than 12 hours, 16%), preservation method if CIT is no more than 24 hours (cold storage, 22%; machine, 17%), recipient race (Caucasian, 23%; black, 11%), original disease, recipient age, recipient sex, donor race, and the quality of early graft function (less than or equal to one month). Factors not significantly influencing 10-year graft survival were panel-reactive antibodies, warm ischemia time, preservation method if CIT was more than 24 hours, and donor sex.(ABSTRACT TRUNCATED AT 250 WORDS)

The validity of the Essen-Möller formulation probability of paternity is supported by demonstrating its correctness in a model genetic system--the ABO system. An analysis was made of 1,393 paternity cases typed uniformly for HLA-A and -B, ABO, Rh, and MNSs, in which the mother named one man only as the child's father and in which both mother and putative father identified themselves as Caucasian. For purposes of analysis, putative fathers not excluded from paternity by the four systems tested were regarded as actual fathers. The joint distribution of observed triplets of ABO phenotypes is shown to be statistically consistent with expected values, and the fractions of "true" fathers for a given triplet closely approximated the probability of paternity calculated using a realistic prior probability. Recent allegations of fallaciousness of the method by Li and Chakravarty and Aickin are discussed in terms of the results presented.

1. Kidney graft survival rates have stabilized over the past 4 years, suggesting that gains achieved with CsA have plateaued. The overall 1-year graft survival is 77% for first cadaver donor transplants, 90% for parental donors, and 93% for HLA-identical sibling donors. Patient survival for all categories is now over 95%. 2. The UNOS 6-antigen match program has resulted in outstanding graft survivals. Of 88 kidneys which were transplanted into first graft recipients, the 6-antigen match kidney had a 1-year graft survival of 91% compared to 74% for the contralateral kidney transplanted locally (p less than 0.008). 3. In highly sensitized patients with more than 80% PRA the shipped 6-antigen matched kidney had a 91% 1-year graft survival rate compared to 72% survival in comparable control patients from the registry (p less than 0.005). In patients with less than 80% PRA, 6-antigen matched kidneys had 90% 1-year graft survival compared to 80% in controls (p less than 0.00001). 4. The spread of 1-year graft survival rates at 68 centers that performed more than 100 transplants was 63-94%. The cumulative graft survival of 6-antigen matches performed at 129 different centers was 90%. Thus, the strong center effect was neutralized by the use of matched transplants. 5. In contrast to the 1% of patients who would receive O-B,DR mismatched transplants on a random basis, if kidneys were shared in the national pool, 74% could receive such a transplant. We therefore propose that a keep one-share one policy be adopted for all kidneys harvested in the United States. If no 0-B,DR mismatched patient is available, both kidneys will be kept by the harvesting center. Since 63% of kidneys are currently being shared with other centers for various reasons, the 75% sharing suggested by the new system should not impose a hardship on transplant centers. The UNOS payback agreement will be replaced by this agreement by which shipping will be done only to achieve excellent matches. 6. In order to achieve a better method of excluding the worst mismatches, an attempt was made to develop a new method of mismatching using amino acid sequences of the HLA specificities. Donor and recipient types can be converted to amino acid sequences and the mismatching done on the basis of amino acids of mismatch at each residue or position. For each residue, specific combinations of amino acid substitutions were examined individually to determine their effect on graft survival. From these studies, a list of "immunogenic" amino acids was prepared, and graft survival was then computed for increasing numbers of amino acids of mismatch.(ABSTRACT TRUNCATED AT 400 WORDS)

1. There was a "transfusion effect" for cadaver kidney transplant recipients and the improvement of 1-year graft survival with transfusions was 7.1% (p0.0002) in 1987. 2. Two or 3 pretransplant transfusions are sufficient to obtain the maximum transfusion effect. 3. In 1988, about a quarter of the patients received first cadaver kidney transplants without any pretransplant transfusions, whereas only 10% were nontransfused during the period between 1981 and 1984. 4. The transfusion effect diminished as patients aged. The increase in 1-year graft survival with transfusions was 17% in patients aged 16-25, 4% in patients aged 46-55, and 1% in patients over 55. 5. Both transfused and nontransfused patients had as high as 83% 1-year graft survival rates when they received 0 A, B, DR-mismatched kidneys. Transfusions improved graft survival by as much as 8% for recipients with mismatched grafts. 6. There was no transfusion effect in recipients of 0 DR-mismatched kidney transplants. Transfusions improved the 1-year graft survival rate by 8-10% for transplant recipients with 1 or 2 DR-mismatched kidneys. 7. The transfusion effect was greater in black (8%) than white (4%) recipients; however, the 77% 1-year graft survival rate for transfused black recipients of 0 DR-mismatched kidneys did not differ from that of transfused whites. 8. Considering the transfusion effect on graft failure rather than graft survival, the failure rate in nontransfused patients could have been reduced by 30% in transplants performed between 1976 and 1979, 17% in transplants from 1980 through 1983, and 21% in transplants since 1984 with blood transfusions.

In 33 renal allograft recipient-donor pairs, B and T lymphocyte complement-dependent cytotoxicity crossmatches and mixed lymphocyte culture (MLC) blocking experiments were performed and the results were correlated with graft outcome. MLC blocking particularly in the unidirectional culture against donor-stimulating cells, was highly correlated with the presence of complement-dependent cytotoxicity antibodies against donor B lymphocytes. Grafts in both MLC blocking and B lymphocyte crossmatch-positive groups fared equally as well as those without positive tests. No difference in graft outcome was noted when the presence or absence of MLC blocking was examined in relationship to positive or negative B lymphocyte complement-dependent cytotoxicity crossmatching.

A new monoclonal antibody, CSLEX1, directed against sialylated Lewisx was tested in parallel with a monoclonal antibody, CSLEA1, directed against sialylated Lewisa antigen. In tests with a solid-phase radioimmune sandwich assay, the sialylated Lewisx monoclonal antibody detected sera from certain cancer patients that were negative with the sialylated Lewisa monoclonal antibody. Some sera from cancer patients showed the reverse reaction. We conclude that the combined use of these two monoclonal antibodies detects a wider range of sera from cancer patients than the use of a single antibody alone. It should be possible in the future to use multiple monoclonal antibodies to increase detection.

A protein in saliva that is resistant to boiling and has a molecular weight greater than 400,000 daltons was found. Antibody against this antigen occurred naturally in about 20% of 92 normal and 334 dialysis patients. This antibody was associated with an early graft failure in studies of 201 first and 133 multiple graft patients. The effect was strong in male patients and absent in female patients. This antimucin antibody may explain some early graft failure in negative crossmatches.

1. The ultimate distribution of 479 consecutive cadaver donor kidneys in the Los Angeles area was examined to determine whether the distribution had been equitable. Half of the kidneys had been allocated by the UNOS point system (or slight modifications thereof) and half by the transplant centers according to their own criteria. 2. With respect to waiting time, the pool of 1,000 was composed of 14% patients who had waited more than 2 years. The UNOS point system forced the transplantation of more patients (27%) who had waited longer than 2 years than the nonpoint system (11%). 3. Although the waiting pool was composed of 28% waiting for retransplantation, the UNOS point system resulted in transplantation of 16% and the nonpoint system, 8%. 4. In the waiting pool, 16% of the patients had cytotoxic antibodies reactive to more than 80% of the panel, whereas 11% of the transplants by the UNOS point system were transplanted into highly sensitized patients and only 2% of the patients transplanted by the nonpoint system were highly sensitized. 5. In Los Angeles, where 11% of the population is Black, 10% of the kidneys transplanted were into Black patients. Since 18% of the waiting pool of patients were Black, some shortfall was noted. However, this can be attributed to the fact that only 7% of the donors were Black. The importance of increasing donation from the Black community is emphasized. 6. Because of the limited pool size of 1,000 patients only a small number of 0 B,DR transplants were achieved.(ABSTRACT TRUNCATED AT 250 WORDS)