Clinics in Immunology and Allergy最新文献

Analysis from the Eurotransplant data base reveals that matching for HLA-A and -B antigens has a beneficial effect not only on cadaveric kidney graft survival but also on patient survival. This beneficial effect can be demonstrated most clearly after five years follow-up time with a sufficient number of donor-recipient combinations in the various HLA-A and -B mismatch categories.

Matching for the HLA-DR determinants also improves kidney graft survival significantly. The best kidney graft survival is obtained when donor and recipient are matched for the HLA-DR determinants as well as for the HLA-A and -B antigens.

Concerning pretransplant blood transfusions, it is unequivocally clear from the prospective study in The Netherlands that one leucocyte-poor blood transfusion is a good pretransplant blood transfusion protocol. Furthermore, transfusions which are depleted of leucocytes, i.e. leucocyte-free blood, do not improve kidney graft survival.

The interaction between the two important factors, HLA-matching and pretransplant blood transfusion, shows that HLA-A and -B matching as well as HLA-DR matching is most apparent in non-transfused recipients, although it should be stressed that the best kidney graft survival is obtained when donor and recipient are well matched for HLA and the recipient has been transfused.

In an attempt to identify patients before transplantation in high or low responders, it can be shown that typing for HLA-DRw6 antigen can be helpful in this respect. HLA-DRw6 positive patients are high responders and should be transplanted with HLA-DRw6 positive kidneys. Furthermore, it can be demonstrated that HLA-DRw6 positive donor kidneys have a better than average graft survival, independent of the match. Good kidney graft survival was obtained with such donors even in the face of one or two HLA-DR mismatches (see Table 8).

In conclusion, the role of HLA-A, -B and -DR matching was, and still is, a very important factor in kidney graft survival. However, they are certainly not the only factors at play. Others, such as clinical management, immunosuppressive treatment, warm ischaemia time, monitoring of T-cell subset ratios, etc., should be considered as well in further analyses (van Es et al, 1983). Predicting renal allograft survival remains extremely difficult, as it is dependent on a multitude of interacting factors.

Recent methods for detecting and quantifying immunoglobulin allotypes are discussed. Application of recombinant DNA technology to the study of immunoglobulin genes and its advantages and disadvantages, compared with the widely-used serological allotyping methods, are presented. Limitations of current disease association studies are mentioned. Anticipated advances in this area, together with the potential basic and clinical significance of findings from such investigations, are discussed.

Glucocorticosteroids (‘steroids’) are widely used as anti-inflammatory agents. They produce a vast array of effects, primarily through their ability to bind to cytosol receptors in most (if not all) nucleated cells in the body. Steroids frequently cause the production of new proteins or increase the synthesis of other proteins.

Steroids cause major changes in the traffic patterns of lymphocytes granulocytes and monocyte-macrophages. These result in neutrophilia and lower blood concentrations of lymphocytes, eosinophils, monocytes and basophils. Such traffic changes, as well as changes in function of these cells, all diminish the influx of cells into inflammatory reactions.

Steroids most useful for systemic anti-inflammatory treatment are short-acting oral preparations such as prednisone. Given in one daily dose, these are inexpensive and effective. Various types of steroid regimens are used for different situations. Adrenal replacement therapy is not useful for inflammatory conditions. Induction of anti-inflammatory conditions usually involves moderately high doses of oral steroids for one to two weeks before tapering. Maintenance of anti-inflammatory control on a long-term basis is often not needed. If it is required, alternate-morning therapy is preferred, although some patients on low-dose daily steroids do not show much inhibition of the hypothalamic-pituitary-adrenal (HPA) axis. Large doses of intravenous corticosteroids (‘pulse therapy’) is useful in a few special situations.

Corticosteroids work in various ways in different conditions. In asthma, they do not impair IgE mechanisms, but exert anti-inflammatory actions and potentiate the effects of β-adrenergic bronchodilators. In immune complex disease, they are antipyretic, vasoconstrictive, impair the release of injurious enzymes from inflammatory cells, are antichemotactic and may interfere with prostaglandin synthesis.

Side-effects of corticosteroids are numerous but many can be avoided by the use of judicious dosing regimens. The controversy over the role of steroids in infections is reviewed.