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GENETICS OF KIDNEY ALLOGRAFT SURVIVAL IN DOGS II. RELEVANCE OF MINOR HISTOCOMPATIBILITY SYSTEMS IN RECIPIENTS WITHOUT IMMUNOSUPPRESSIVE THERAPY1

A. Bart Bijnen, D.L. Westbroek, Hugo Obertop, Hero van Urk, H. M. Vriesendorp

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Abstract

An attempt is made to define the importance of non-SD (serologically defined) and non-LD (lymphocyte-defined) antigens in kidney allograft survival in nonimmunosuppressed dogs. In beagles, graft survival is prolonged by SD and LD matching in littermate donor-recipient pairs, but to a lesser extent in similarly matched nonlittermate donor-recipient combinations. More differences for non-SD and non-LD antigens (presumably minor histocompatibility antigens) in nonlittermates are probably responsible for the shorter survival times in this group. The cumulative effect of these differences is comparable to major histocompatibility differences since the survival times of the SD- and LD-matched nonlittermate kidneys are similar to the survival times of kidneys from littermate donors mismatched for one haplotype of the major histocompatibility complex (MHC). SD and LD matching is even less effective in unrelated mongrels than in nonlittermate beagles. This may be attributable to a greater heterogeneity of non-SD and non-LD systems in mongrels, or inaccuracies in the current dog LD and SD typing. Immunogenetic analysis of the 17% incidence of prolonged kidney allograft survival in MHC-identical littermate donor-recipient pairs provides a rough impression of the polymorphism of relevant minor histocompatibility systems in beagles in our colony (for instance, three systems with three alleles each may explain the results). Sex-linked histocompatibility systems do not seem to play a role in unimmunized nonimmunosuppressed recipients. It is stressed that care should be taken to extrapolate observations obtained in a model without immunosuppression to models or situations in which such agents are used.

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An attempt is made to define the importance of non-SD (serologically defined) and non-LD (lymphocyte-defined) antigens in kidney allograft survival in nonimmunosuppressed dogs. In beagles, graft survival is prolonged by SD and LD matching in littermate donor-recipient pairs, but to a lesser extent in similarly matched nonlittermate donor-recipient combinations. More differences for non-SD and non-LD antigens (presumably minor histocompatibility antigens) in nonlittermates are probably responsible for the shorter survival times in this group. The cumulative effect of these differences is comparable to major histocompatibility differences since the survival times of the SD- and LD-matched nonlittermate kidneys are similar to the survival times of kidneys from littermate donors mismatched for one haplotype of the major histocompatibility complex (MHC). SD and LD matching is even less effective in unrelated mongrels than in nonlittermate beagles. This may be attributable to a greater heterogeneity of non-SD and non-LD systems in mongrels, or inaccuracies in the current dog LD and SD typing. Immunogenetic analysis of the 17% incidence of prolonged kidney allograft survival in MHC-identical littermate donor-recipient pairs provides a rough impression of the polymorphism of relevant minor histocompatibility systems in beagles in our colony (for instance, three systems with three alleles each may explain the results). Sex-linked histocompatibility systems do not seem to play a role in unimmunized nonimmunosuppressed recipients. It is stressed that care should be taken to extrapolate observations obtained in a model without immunosuppression to models or situations in which such agents are used.

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Available abstract

An attempt is made to define the importance of non-SD (serologically defined) and non-LD (lymphocyte-defined) antigens in kidney allograft survival in nonimmunosuppressed dogs. In beagles, graft survival is prolonged by SD and LD matching in littermate donor-recipient pairs, but to a lesser extent in similarly matched nonlittermate donor-recipient combinations. More differences for non-SD and non-LD antigens (presumably minor histocompatibility antigens) in nonlittermates are probably responsible for the shorter survival times in this group. The cumulative effect of these differences is comparable to major histocompatibility differences since the survival times of the SD- and LD-matched nonlittermate kidneys are similar to the survival times of kidneys from littermate donors mismatched for one haplotype of the major histocompatibility complex (MHC). SD and LD matching is even less effective in unrelated mongrels than in nonlittermate beagles. This may be attributable to a greater heterogeneity of non-SD and non-LD systems in mongrels, or inaccuracies in the current dog LD and SD typing. Immunogenetic analysis of the 17% incidence of prolonged kidney allograft survival in MHC-identical littermate donor-recipient pairs provides a rough impression of the polymorphism of relevant minor histocompatibility systems in beagles in our colony (for instance, three systems with three alleles each may explain the results). Sex-linked histocompatibility systems do not seem to play a role in unimmunized nonimmunosuppressed recipients. It is stressed that care should be taken to extrapolate observations obtained in a model without immunosuppression to models or situations in which such agents are used.

Key concepts: Minor histocompatibility antigen, Histocompatibility, Histocompatibility Testing, Major histocompatibility complex, Immunosuppression, Immunology, Antigen, Biology

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GENETICS OF KIDNEY ALLOGRAFT SURVIVAL IN DOGS II. RELEVANCE OF MINOR HISTOCOMPATIBILITY SYSTEMS IN RECIPIENTS WITHOUT IMMUNOSUPPRESSIVE THERAPY1 — Research Paper | ScholarLens