G. R. D. Catto

THE FETUS AS AN ALLOGRAFT: EVIDENCE FOR PROTECTIVE ANTIBODIES TO HLA-LINKED PATERNAL ANTIGENS

Non-cytotoxic antibodies to paternal B lymphocytes were detected in sera from 11 of 11 multiparous women and from 11 of 16 normal primigravidae during the first trimester of pregnancy. These antibodies were not, however, detected in sera from 9 of 10 women of comparable gestation at the time of spontaneous abortion. By means of a rosette inhibition assay, the difference in antibody activity between the primigravidae (mean 37.9 +/- 19%, median 36.5%) and the women subject to spontaneous abortion (mean 7.3 +/- 11.6%, median 0%) was statistically significant. This antibody activity was not directed to the known HLA specificities (HLA--A, B, C, or DR), but linkage to the HLA gene complex was suggested by family studies. These results provide evidence for an HLA-linked antigen system not defined by conventional tissue-typing techniques. Fetomaternal disparity at this antigenic site may be important for successful pregnancy.

HAEMODIALYSIS FOR A HAEMOPHILIAC WITH HUMAN IMMUNODEFICIENCY VIRUS

Long-term dialysis treatment has been undertaken only infrequently in patients with haemophilia and end-stage renal disease. This is the first report of maintenance haemodialysis in a haemophiliac with serological evidence of human immunodeficiency virus (HIV). In March 19 8 7 a 44-year-old male with severe haemophilia A (factor VIIIc level less than 1%) required dialysis for endstage renal disease. Although renal biopsy was not performed it was presumed that the renal failure was due to chronic glomerulonephritis, on the basis of longstanding renal impairment and smooth shrunken kidneys on ultrasound examination. From October 1985 he had been persistently seropositive for HIV antibodies, and in June 1987 developed HIV antigenaemia. He had not developed any sequelae of HIV infection, which was thought to have been contracted from factor VIII infusions. When end-stage renal disease developed, in March 1987, an arteriovenous shunt was inserted, under factor VIII control, between the right cephalic vein and radial artery. Apart from some bleeding during and after the initial dialysis, there have been no complications with the shunt. The patient now dialyses for 6 h, twice-weekly. He receives 1000 units of factor VIII concentrate immediately after dialysis, and heparin has not been required during dialysis. The patient uses a designated haemodialysis machine, in a ward separate from the main dialysis unit. Dialysis staff wear masks, gloves, gowns and goggles when initiating and terminating dialysis, and shower immediately after dialysis. Although the incidence of end-stage renal disease does not appear significantly increased for patients with haemophilia (Small et al. 1982) the paucity of reports in the literature perhaps suggests that dialysis is rarely undertaken for such patients, possibly because of anticipated problems with vascular access and haemostasis. In practice we, and others (Koene et al, 1977; Sechas et al, 1981), have found that such difficulties are relatively easily overcome. Moreover, successful renal transplantation has been described in a haemophiliac with a factor VIIIc concentration of less than 1% (Koene et al. 1977). Despite the extra costs in terms of accommodation, equipment and staffing, maintenance haeniodialysis treatment was undertaken in preference to continuous ambulatory peritoneal dialysis (CAPD). There were several reasons for this decision. CAPD has the advantage of allowing treatment at home but was considered to be associated with an increased risk of infection in an already immunocompromised patient and the possibility of serious intraor retroperitoneal bleeding. For an individual with severe haemophilia. evidence of HIV infection and many intercurrent problems, there seemed to be an advantage in having a designated hospital base with nursing staff experienced in the infection control procedures outlined in the Rosenheim report (Rosenheim, 19 72). An arteriovenous shunt was chosen as vascular access because it was thought that the insertion of needles into an arteriovenous fistula would cause repeated haematomata formation, and therefore permanent occlusion, as previously described (Sechas et al, 1981). Moreover, the frequent use of needles in an HIV antibody positive patient was considered an added potential risk to staff. Haemodialysis has thus far proved to be a practical and worthwhile treatment for this haemophiliac with asymptomatic HIV infection. The incidence of end-stage renal failure increases markedly for patients with AIDS, and despite haemodialysis such patients have a poor prognosis (Rao et al. 1987). There, is as yet, no data on the development of renal failure for patients with asymptomatic HIV infection. It is unlikely, however, that this patient’s renal disease was related to HIV, as he was known to have longstanding and progressive renal impairment prior to contracting HIV infection.

Identification of subpopulations of T lymphocytes and Ia positive B lymphocytes using a rosette assay based upon the biotin-avidin interaction

Bovine erythrocytes were coated with avidin using a chromic chloride coupling technique and used successfully in an indirect rosette assay to identify and quantitate: (a) T-lymphocyte helper and suppressor subpopulations, and (b) Ia positive B-lymphocyte populations. Using mouse monoclonal antibodies to the T-lymphocyte markers OKT3, OKT4, and OKT8 it was shown that the proportion of OKT4 and OKT8 positive cells were respectively 60.9 and 39.2% of the total OKT-3 positive T lymphocytes. In a similar way, using a monoclonal anti-human Ia antibody, the percentage Ia positive cells in B-lymphocyte enriched preparations was shown to vary between 18 and 55% for normal peripheral blood and 31 and 58% for chronic lymphocytic leukaemia derived peripheral blood.

Non-cytotoxic alloantibodies defined by the EA rosette inhibition assay.

Sera from both transfused individuals and pregnant women mediated inhibition of Fc-rosette formation. Both normal blood B lymphocytes and chronic lymphocytic leukemia cells were used as targets. Inhibition was not related to the presence or absence of lymphocytotoxic antibodies. When tested against a panel of B lymphocytes these sera displayed selective reactivity in keeping with the recognition of allospecific determinants. No association between the target antigen(s) and classically defined MHC-coded structures was evident. Heteroantibodies to both class I and class II MHC structures as well as beta 2-microglobulin also mediated FcR blockade. However, unlike the alloantisera tested, these antibodies displayed no restriction in their reactivity toward individual target cells.