Lymphocytotoxins in sera from highly sensitized multiparous dialysis patients: antibody class, relationship with the HLA and with paternal antigens

D J Propper, W A Leheny, S J Urbaniak, G R Catto, A M Macleod

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Abstract

1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70% of a panel of lymphocytes from 24 donors (panel reactivity greater than 70%). 2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens. 3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50% of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80% was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens. 4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class. 5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies. 6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to antigens in blood transfusions from donors who share paternal class I specificities.
Original languageEnglish
Pages (from-to)87-93
Number of pages7
JournalClinical Science
Volume80
Issue number2
Publication statusPublished - 1 Feb 1991

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Immunoglobulin Isotypes
Antilymphocyte Serum
Dialysis
Antigens
Serum
Histocompatibility Antigens Class I
Lymphocytes
K562 Cells
Dithiothreitol
Histocompatibility Antigens Class II
HLA Antigens
Blood Donors
Blood Transfusion
Autoantibodies
Allografts
Digestion
Immunoglobulin G
Monoclonal Antibodies
Tissue Donors
Kidney

Keywords

  • Adult
  • Antilymphocyte Serum
  • Female
  • Graft Survival
  • HLA Antigens
  • Histocompatibility Testing
  • Humans
  • Hypersensitivity, Immediate
  • Kidney Transplantation
  • Middle Aged
  • Parity
  • Renal Dialysis

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Lymphocytotoxins in sera from highly sensitized multiparous dialysis patients: antibody class, relationship with the HLA and with paternal antigens. / Propper, D J; Leheny, W A; Urbaniak, S J; Catto, G R; Macleod, A M.

In: Clinical Science, Vol. 80, No. 2, 01.02.1991, p. 87-93.

Research output: Contribution to journalArticle

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abstract = "1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70{\%} of a panel of lymphocytes from 24 donors (panel reactivity greater than 70{\%}). 2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens. 3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50{\%} of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80{\%} was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens. 4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class. 5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies. 6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to antigens in blood transfusions from donors who share paternal class I specificities.",
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N2 - 1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70% of a panel of lymphocytes from 24 donors (panel reactivity greater than 70%). 2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens. 3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50% of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80% was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens. 4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class. 5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies. 6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to antigens in blood transfusions from donors who share paternal class I specificities.

AB - 1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70% of a panel of lymphocytes from 24 donors (panel reactivity greater than 70%). 2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens. 3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50% of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80% was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens. 4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class. 5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies. 6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to antigens in blood transfusions from donors who share paternal class I specificities.

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