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There is almost no data from the glomeruli of allografted kidneys with respect to changes in the CR-1 (C3b) receptor expressed on glomerular podocytes. We studied 22 renal graft biopsies from rejecting and stable allografts, using a panel of monoclonal antibodies. We found that the CR-1 expression was decreased in a focal and segmental fashion in some biopsies, particularly in rejecting kidneys. These changes correlated with the intensity of glomerular mononuclear cell infiltration, but in contrast no correlation was seen with peripheral capillary wall deposition of complement (C3). Thus, some active process is occurring in the glomeruli of rejecting grafts which affects the expression of the CR-1 receptor.

In a blind trial, 77 patients were randomised to receive first cadaver kidney allografts that had been perfused either with a pair of CD45 monoclonal antibodies (mAbs), in an attempt to reduce the immunogenicity of passenger leucocytes, or with control human albumin solution. No complications of mAb perfusion were observed. Patient and allograft survival were similar in both groups. Rejection episodes were recorded in 7 (18%) of the patient with mAb perfused allografts compared with 24 (63%) of the controls.

We have previously reported a genetic susceptibility to a scleroderma-like disorder in a group of workers exposed to polyvinyl chloride and this susceptibility could be mapped to the major histocompatibility complex area of the 6th chromosome. To date no genetic studies have been reported comparing affected with unaffected workers. We report such data and discuss it in the light of our previous findings in vinyl chloride exposed patients and in patients with classical scleroderma. Our results suggest that susceptibility to this disorder is increased in the presence of HLA-DR5 or of a gene in linkage disequilibrium with it and an antigen associated with the haplotype A1 B8, while DR3 favours progression of the disease.

Most but not all subjects with the narcoleptic syndrome have the human leukocyte antigen (HLA) DR2 (and DQ1). The narcolepsy-DR2 association is the highest disease-HLA linkage known, and occurs in nonfamilial as well as familial cases of the narcoleptic syndrome. In other forms of daytime drowsiness, there is no relationship with a specific HLA, although some subjects considered to have "essential" hypersomnolence probably have the narcoleptic syndrome. The cause of the narcoleptic syndrome remains unknown, although in a few instances the condition follows infection. There is no evidence for a circulating sleep factor in the blood or in the cerebrospinal fluid of narcoleptic subjects, and no unequivocal marker of cellular immunity has yet been found. However, a few subjects with the narcoleptic syndrome have oligoclonal bands or raised immunoglobulin concentration in the cerebrospinal fluid. It is highly likely that the narcoleptic syndrome is an immune-mediated disorder, occurring in a genetically susceptible (DR2/DQ1-positive) subject.

The incidence of extended haplotypes of the Major Histocompatibility Complex was compared between 20 probands with RA, their unaffected family members, and 42 controls. One haplotype only, HLA-Bw62 BfS C4A*3 C4B*3 DR4 GLO2, was significantly increased in the patient group, whereas HLA-B7 BfS C4A*3 C4B*1 DR2 GLO1, which was the most common haplotype in the control groups, was absent. The immunoglobulin allotype Glm(2) was significantly increased in frequency in the RA patients, and analysis showed that of the seven patients carrying Bw62-DR4, five were G1m(2) positive. Further, the increase in frequency of the phenotype Gm(1,2,17,21,3,5,23) was also significant and was carried by two of four probands with the extended haplotype HLA-Bw62 BfS C4A*3 C4B*3 DR4 GLO2 and by one proband also bearing this haplotype but with a null allele at the C4A locus. The striking association of G1m(2) and Bw62 with DR4 in our patients suggests that in interaction of immunoglobulin genes with DR4 is stronger when DR4 is associated with particular haplotypes rather than with DR4 in general.

In order to study the changes in T lymphocyte subpopulations in both allografts and peripheral blood of patients following renal transplantation, we have examined 72 fine needle allograft aspirates and 56 peripheral blood samples from 24 patients during the first month following transplantation. The patients were studied before, during and after rejection episodes. Monoclonal antibodies directed against T helper (TH) and T cytotoxic/suppressor (TCS) cells were used to identify lymphocyte subpopulations in the allograft aspirates and peripheral blood. The ratio of TH:TCS cells in both the allograft aspirates and peripheral blood decreased significantly (p less than 0.01) during the three days before rejection became clinically manifest. During rejection, the aspirate TH:TCS ratios, but not the peripheral blood TH:TCS ratios, remained depressed. Following successful treatment for rejection, the aspirate TH:TCS ratios returned to levels found in non-rejecting allografts. However, in the allografts which were lost as a result of rejection or had persistent rejection despite treatment, the aspirate TH:TCS ratios, but not peripheral blood TH:TCS ratios, remained significantly low (p less than 0.01) when compared with the successfully treated allografts. Our study indicates that TH:TCS ratios, particularly in allograft aspirates, may be of value in predicting the onset and outcome of renal allograft rejection.

10 highly and persistently sensitised patients awaiting renal transplantation underwent extracorporeal immunoadsorption to remove anti-HLA antibodies. 7 patients have since received transplants. Only 1 allograft has been lost because of rejection, and there have been no serious side-effects attributable to treatment. Extracorporeal immunoadsorption may therefore be of considerable value in the management of highly sensitised patients.