Lars U. Lamm

Genetics of complement C4. Two homoduplication haplotypes C4S C4S and C4F C4F in a family

SummaryA family in which two homoduplicated C4 haplotypes (or supergenes) segregate is described. One haplotype C4F*3 C4F*2.2 is composed of two C4F alleles and the other C4S*5.1 C4S*1 of two C4S alleles. The C4F duplication haplotype is a partial inhibitor of the Rodgers antigen, and judged from our family and population material, it seems to be rather frequent and associated with HLAB*35, Bf*F, and HLAD/DR*1. The C4S duplication haplotype is Rg(a-) and is not identified in individuals without another S, Ch(a+) variant.

Family studies of complement C4 and HLA in man.

SummaryAt least 12 different C4 gene products with a three band pattern have been identified after electrophoresis of sera pretreated with neuraminidase.Segregation analysis showed at least 12 different C4 haplotypes (or supergenes), of which five represent a single gene product and seven are duplications each composed of an F and an S gene. The data analyzed with respect to linkage showed one recombinant between the C4 and the HLAB loci in 154 meioses giving a map distance of C4 HLAB of 0.6 cM. Another recombinant between the C4 and the HLAD loci was found in 101 meioses giving a map distance of C4 HLAD of 1.0 cM.Linkage disequilibrium was found between at least eight C4 haplotypes and certain alleles at the HLAB as well as the HLAD loci. Examinations of 15 families selected through a proband with HLAA 25, HLAB 18 and C2*Q0 showed that in almost all cases a slight variant of the C4 supergene F3S2 followed the haplotype HLAA*25 HLAB*18 C2*Q0. No associations were found between the two duplications C4F*3 C4S*2 and C4F*3 C4S*1 and the HLA loci. These findings may indicate that these C4 haplotypes were the original ones preceding the other C4 haplotypes.

SIGNIFICANT EFFECT OF HIGH-RESOLUTION HLA-DRB1 MATCHING IN HIGH-RISK CORNEAL TRANSPLANTATION1

The effect of HLA matching in corneal transplantation is still--after numerous of studies--disputable. We investigated the effect of DRB1 matching in high-risk cases with vascularization and/or retransplantation. Only class II antigens were matched because we were unable to obtain donor lymphocytes for HLA typing. Typing was performed on DNA isolated from the ocular tissues up to 24 hr after death. When this study was initiated, DNA-based methods had been developed only for class II typing. The first part of the study concerns 74 cases with at least 3 years of observation fully matched for 17 DRB1 specificities detected using restriction fragment-length polymorphism. This showed an improved long-term graft survival of 72% compared with 45% in a historical control group of 23 comparable cases. In the second part of the study, stored DNA samples from the restriction fragment-length polymorphism-matched donor-recipient pairs were subjected to retyping with a new method based on sequence-specific polymerase chain reaction. It was possible to split DRB1*01, *04, and *11 in 3, 14, and 5 alleles, respectively. The matching was then re-assigned taking all splits into account. This showed that 36 cases had at least one incompatibility, whereas 38 cases were fully compatible. The long-term graft survival rate was 79% in the matched group compared with only 59% in the mismatched group, which is significantly different at P=0.032. This retrospective, but blinded, randomized study is strong evidence for the effect of matching and may give scope for international collaboration to obtain completely matched corneas for this group of patients.

HLA‐DR/RFLP compatible corneal grafts

Abstract. Fifty‐one elective high risk transplantations were matched according to HLA/DR antigens and RFLP‐subtypes. The 18 months survival of the grafts are 93% in the matched group compared to 50% in a non‐matched compatible historical control group.

Genetic studies of complement C4 in man

SummaryA C4 variant found in about 5% of the population is described. The fast-moving part of this variant is governed by an allele (Fx) codominant to F. The Fx allele is in very strong linkage disequilibrium with HLA-B17 as the linkage disequilibrium parameter accounted for nearly 100% of the haplotype frequency of B17, Fx. The strong association is also evidenced by the study of 11 families segregating for the Fx allele. There was no instance of recombination between C4 and HLA in 36 informative meioses.