J. D'Amaro

Immunogenetic heterogeneity of rheumatoid arthritis.

Association of HLA-DR4/Dw4 with rheumatoid arthritis (RA) is well established, but conflicting data exist on a possible association with the severity of the disease, including its extra-articular manifestations. In order to investigate whether a subgroup of RA is preferentially associated with DR4, HLA typing was performed in two groups of patients with severe extra-articular manifestations (Feltys syndrome and histologically proved leucocytoclastic vasculitis), patients with severe joint destruction (seropositive and seronegative), a group with only mild joint destruction, and in healthy controls. The frequency of HLA-DR4 was significantly raised in all patient groups compared with that in healthy controls. The two groups with severe extra-articular manifestations, however, both had a DR4 frequency of 92%, which was significantly (p = 0.002) higher than the 62.7% found in the remaining patients. No significant differences were observed between severe or mild joint destruction and seropositivity or seronegativity in the groups without the above-mentioned extra-articular manifestations. From these data we concluded that DR4 is preferentially associated with severe extra-articular disease manifestations of RA. This observation provides an immunogenetic basis for the disease heterogeneity and for the immunological analogy between RA and leprosy.

Effect of HLA-A and HLA-B Matching on Survival of Grafts and Recipients after Renal Transplantation

Data on the effect of HLA-A and HLA-B matching between unrelated donors and recipients focus mainly on graft survival. After linking the follow-up data of the European Dialysis and Transplant Association and those of the Eurotransplant Foundation, the effect of HLA-A and HLA-B matching on recipient survival could be studied. Recipients of well-matched kidneys--i.e., without mismatches for the HLA-A and B antigens--had 51 per cent graft survival at five years, whereas recipients of grafts mismatched for four antigens had 32 per cent graft survival at five years. The overall P value between the five different mismatch classes was 0.0005. Patient survival at five years was 72 per cent in recipients of a kidney without HLA-A and B mismatches and 54 per cent in recipients of a completely mismatched donor kidney (overall, P = 0.001). These results suggest that matching for the HLA antigens has a beneficial long-term effect not only on renal-allograft survival but also on patient survival.

HLA C ASSOCIATIONS WITH ACUTE LEUKAEMIA

Frequencies of HLA A, B, C, and DR antigens were calculated in 1009 leukaemia patients, all of whom had been treated with bone-marrow transplantation and reported to the International Bone Marrow Transplant Registry. Cw3 (relative risk = 2 X 26, p = 0 X 00002) and Cw4 (relative risk = 2 X 18, p = 0 X 00003) were significantly associated with acute leukaemia (p values adjusted for multiple comparisons). Cw3 (relative risk = 2 X 97, p = 0 X 00002) and Cw4 (relative risk = 2 X 10, p = 0 X 004) were also significantly associated with acute lymphoblastic leukaemia and Cw4 was significantly associated with acute myelogenous leukaemia (relative risk = 2 X 39, p = 0 X 0003). The data suggest that Cw3 and Cw4 may be markers for leukaemia susceptibility genes, genes that code for low immune responsiveness to putative leukaemia viruses, or genes that regulate the response to chemotherapy and, therefore, the attainment of remission, since most of these patients underwent transplantation during remission.

Cell membrane polymorphisms coded for in the HLA-D/DR region I. Relation between D and DR

The relation of HLA-D and -DR determinants was studied in Dutch Caucasoids. The recognition of subgroups of DR4, DR5, and DR7, and the specificities LB12 and LB13 are described. Phenotype and gene frequencies and a Hardy--Weinberg analysis of DR and local (LB) B-cell groups are given. Excellent correlation between D and DR typing was obtained when HTCs were studied by selected B-cell antisera. When the same sera were used to type a panel of D typed cells, the correlation was decreased (with the exception of DR3 and Dw3). In the case of discrepancies the DR specificity, but not the corresponding D specificity, always could be found and not the other way around. The data fit best the assumption that HLA-D and -DR are carried by the same molecule, although they might be different determinants on this molecule. A number of possible explanations for the observed discrepancies has been given.

HLA antigens in patients with chronic inflammatory demyelinating polyneuropathy

In a group of 52 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP), no significant associations were found with any of the HLA-A, B, C, DR or DQ antigens. No HLA association was found between the presence or absence of anti-neural antibodies or between the group of patients improving or not improving after intravenous immunoglobulin. These findings mean that we could not confirm results from the literature that suggest that CIDP is associated with the HLA-A1,B8,DR3 haplotype or--as recently was suggested--with the HLA-Cw7 or DR2 antigen.

HL-A antigens and breast cancer

Abstract HL-A antigens were determined in 200 breast cancer patients and 200 matched controls. No significant differences were found between the frequencies of HL-A antigens in the two groups. Also, when the patients were divided according to several clinical criteria, no significant associations with any of the HL-A antigens were observed.