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Biomedical subjects

A Ting

Publications and source records attributed to A Ting.

At least 19 recordsLinked to original sources

Development of donor-specific B lymphocyte antibodies after renal transplantation. No correlation with graft outcome.

Serum samples from 66 recipients of first cadaver donor renal transplants were screened for cytotoxic antibodies to normal T and B lymphocytes and B lymphocytes from chronic lymphocytic leukaemia patients. In addition, the sera of 44 patients were tested with the B lymphocytes of their respective donors. Donor-specific antibodies were found in 10 of 16 (63%) recipients who had lost their transplant within 2 months, and in 17 of 28 (61%) patients with functioning transplants at 2 months. No correlation was found between the development of B lymphocyte antibodies (either against the panel or the donor) and the onset of an acute rejection episode. In the 17 patients with a successful transplant and donor-specific antibodies, six (35%) had not experienced a rejection episode and another seven patients developed their antibodies after the appearance of the first rejection episode. Thus, our results show that the appearance of donor-specific B lymphocyte antibodies after transplantation is not indicative of graft failure or predictive of acute rejection episodes. However, the common occurrence of such antibodies raises questions concerning the nature of the antigenic stimulus, the specificity of the antibodies, and their role (if any) in transplantation.

Antibodies

Matching for B-cell antigens of the HLA-DR series in cadaver renal transplantation.

Stored and fresh lymphocytes from 84 donors and recipients of cadaveric renal allografts have been retrospectively typed for 7 HLA-DR antigens. The match between donor and recipient was graded as 2, 1, or 0 identities. Graft function was assessed by (i) failure or success at 3 months, (ii) serum-creatinine at 3 and 6 months, and (iii) the number of rejection episodes occurring within 3 months. All 4 recipients with 2 identities had good 3-month function, and all are still functioning at 5--19 months. Recipients with 1 identity had both a higher success-rate and better quality of function than those with 0 identities. Although the differences do not reach significance, a continuing prospective study of HLA-DR matching is justified, with particular emphasis on performing transplants where two DR antigens are shared between donor and recipient.

B-Lymphocytes

Reactivity of autolymphocytotoxic antibodies from dialysis patients with lymphocytes from chronic lymphocytic leukemia (CLL) patients.

Autolymphocytotoxic antibodies are found commonly in dialysis patients and these autoantibodies may be directed against T and B lymphocytes or just B lymphocytes. However, these autoantibodies react with a low frequency or not at all against chronic lymphocytic leukemia cells, and are not absorbed by autologous erythrocytes. Thus, a number of positive crossmatches between donor and recipient may be attributable to autoantibodies. Six renal transplants have been carried out in the presence of such a positive crossmatch against donor B lymphocytes, including one against donor T lymphocytes, with a successful graft outcome. Thus, the indications for renal transplantation in the presence of a positive crossmatch between donor and recipient are becoming better defined.

Autoantibodies

Renal transplantation in the presence of a positive crossmatch.

Eighteen renal transplants have been performed prospectively in the presence of a positive serologic crossmatch against donor B lymphocytes. Four transplants have failed, three from rejection and one from renal artery thrombosis. Fourteen are functioning at 3-17 months after transplant. Thus, a renal transplant may be performed in the presence of a positive B-cell crossmatch in most instances without immediate graft rejection.

Graft Rejection

Renal transplantation and B-cell cross-matches with autoantibodies and alloantibodies.

Of 51 cadaveric kidneys transplanted between June, 1976, and June, 1977, 18 were transplanted in the presence of a positive cross-match against the donor's B lymphocytes. 11 of these positive cross-matches were due to alloantibodies and 7 due to autoantibodies. Autoantibodies were defined not only on the basis of autoreactivity with B lymphocytes but also by their absent or restricted reactivity with lymphocytes from patients with chronic lymphocytic leukaemia. Transplants in 8 of 11 patients with a positive alloantibody-B-cell cross-match and in 6 of 7 patients with a positive autoantibody-B-cell cross-match were successful at 3 months. These success-rates were no different from those found in patients with a negative B-cell cross-match. Thus, renal allografts may be performed with a reasonable assurance of success in the presence of a positive B-cell cross-match whether due to autoantibodies or to alloantibodies.

Antibodies, Heterophile

Correlation of HLA and thyroid antibodies with clinical course of thyrotoxicosis treated with antithyroid drugs.

The prevalence of HLA-B8 in thyrotoxic (Graves' disease) patients who relapsed after withdrawal of antithyroid drugs was high (69%) compared with that in patients who remained in remission (40%) and in healthy controls (28%). B8-positive patients were 1-8 times more likely to relapse after withdrawal of drug therapy than B8-negative patients. The persistence of thyroid microsomal antibodies after withdrawal of therapy correlated significantly with the presence of HLA-B8. This association was more pronounced in patients who remained in remission. From this it might be assumed that B8 is also associated with the persistence of thyroid T.S.H. (thyroid-stimulating hormone) receptor stimulating antibodies. In view of these findings, it is suggested that patients who are thyrotoxic might be typed for HLA, and those who are B8-negative could be given a trial of long-term antithyroid drug therapy.

Adolescent

Renal transplantation and a positive serological cross-match.

A renal transplant involving a recipient with a positive serological cross-match against donor lymphocytes generally results in hyperacute rejection of the graft. 13 cadaveric renal transplants were performed in recipients with a known positive serologic cross-match against donor B lymphocytes. 12 of these serological cross-matches were positive against donor blood, node, or spleen lymphocytes, but the reactivity was directed against donor B lymphocytes only. 3 transplants failed, 2 because of rejection and 1 because of renal-artery thrombosis. 10 transplants are functioning, 6 to 42 weeks after the operation. Of these 10 successful grafts, 3 had no acute rejection episodes, while 7 had an early acute rejection episode which responded to treatment. Histologically, the grafts showed a cellular rejection, similar to that in enhanced renal allografts in the rat. It is possible to transplant a kidney in a high-risk patient with a positive B lymphocyte cross-match with a low risk of failure. In addition active enhancement of the graft might sometimes occur.

Acute Disease

Human B-lymphocyte antigens expressed by lymphocytic and myelocytic leukemia cells. II. Detection by human anti-B-cell alloantisera.

The majority of human lymphocytic and myelocytic leukemia cells express a polymorphic antigen that is found on peripheral blood B-lymphocytes and cultured lymphoblastoid B-cell lines. These B-lymphocyte antigens were detected by 34 human alloantisera that were repeatedly absorbed with pooled platelets to remove all activity against HLA antigens and T-lymphocytes. Absorption studies indicated that a common antigen was present on both B-lymphocytes and positive leukemia cells. Leukemia cells could be subdivided into two groups based on the presence of the B-lymphocyte antigen. Fourteen of 18 acute myelocytic leukemia cells, 10 of 13 acute lymphoblastic leukemia cells, 4 of 6 chronic myelocytic leukemia cells, and 2 of 2 chronic lymphocytic leukemia cells were positive. This group of leukemia cells also reacted with rabbit anti-B-cell sera raised to papain digests of spleen cell membranes. F(ab')2 fragments of the rabbit antsera were shown to specifically block the reactions of the human antisera against B-cells and leukemia cells. These results suggested that the rabbit and human anti-B-cell sera were reacting with identical molecules. This conclusion was supported by immunoprecipitation data.

Adult

Development of Rh-specific maternal autoantibodies following intensive plasmapheresis for Rh immunisation during pregnancy.

Two cases of autoantibody formation following large volume plasmapheresis for rhesus immunisation during pregnancy are described. In each case the autoantibody was directed against the Rh complex but showed a preference for G-positive cells. It is postulated that repeated plasmapheresis in the presence of persistent antigenic stimulation has removed a feedback inhibition of the immune response. The specificity of the alloantibody has broadened resulting in cross-reactivity against self-antigens. The possible implications of these cases in relation to autoimmunity are discussed.

Adult