Erythroid HLA Class I Expression in 300 Patients with Haematological, Renal and Rheumatological Disorders

Abstract

The expression of HLA class I was assessed on erythrocytes by haemagglutination with monoclonal antibodies to monomorphic epitopes on the heavy and light (ß2-microglobulin) chains. Previously, enhancement of HLA class I expression was observed on erythrocytes of many patients with systemic lupus erythematosus (SLE) and chronic lymphatic leukaemia (CLL), and we have now tested erythrocytes from patients (and 130 normal controls) with other auto-immune diseases and renal and haematological disorders. The striking enhancement in patients with SLE and CLL was confirmed. A significant increase in expression was also observed in aplastic anaemia patients following bone marrow transplantation and in renal patients with primary glomerulonephritis who had received a transplant. No class I was expressed by erythrocytes from many patients with inherited haemoglobinopathies and high reticulocyte counts, which suggests that the enhancement in SLE patients cannot be accounted for by immature or young erythrocyte populations. The distribution of HLA-A and -B types in the patients with enhanced class I expression did not relate to those antigens previously detected more frequently on erythrocytes, B7(Bg(a)), B17(Bg(b)), A28(Bgc), B8 or A10, and the enhancement was not associated with any particular HLA types.

Human leukocyte antigens (HLA) class I (Bg) on red cells studied with monoclonal antibodies

“…Our data have addressed the HLA problem with the aid of MoAbs and modern laboratory technoloy. 16,18,19,23,27 By estimating the numbers of class I molecules on RBCs in a radioligand binding assay, data have been obtained that support the concept of an intrinsic membrane molecule rather than one acquired from plasma.27 SLE patients with high counts of HLA molecules on RBCs do not show an equivalent increase of HLA in their plasma; nor do their RBCs gain HLA molecules with aging in circulation. The structure of HLA in SLE patients and normal persons appears to be the same23 and the enhancement is simply reflecting a quantitative difference.…”

“…38 It is not clear why HLA class I is enhanced in RBCs of some normal donors31 and several diverse patient groups.18,19,30, 35 We have suggested that RBCs are sensitive indicators of some unknown immunological reaction. 19 Cytokines, such as y-interferon, can enhance expression of class I39 and raised levels of interferons have been reported in SLE patients. 40 The enhanced class I we detect may therefore be remnants from the stimulated nucleated precursors.…”

“…The reason for the fourfold increase in HLA-B7 molecules on RBCs is not understood, but it is not related to the enhancement seen in disease groups studied, as no association between HLA types and enhancement was observed. 19 While HLA on RBCs may still represent a nuisance to blood bankers and reference laboratories, the theoretical understanding of their structure has been largely clarified by recent work using MoAbs in a wide range of techniques.…”

“…MoAbs have been used in radioimmunoassay,9 flow cytometry,9,16,17 and hemagglutination tests. [18][19] This paper is an attempt to review some recent work from London, that was initiated by the discovery of strong HLA on the RBCs of a patient deficient in the fourth component of complement (C4) with systemic lupus erythematosus (SLE),20 and subsequently in other SLE patients who were not C4 deficient. 18 To simplify most of our studies, we selected MoAbs specific for monomorphic epitopes on the a3 and ß2-M domains of class I.…”

Porcine red blood cells as a source of blood transfusion in humans

“…Human RBCs can express major histocompatibility complex class 1 antigens [14], but expression is usually clinically insignificant except perhaps in certain disease states [15,16]. Similarly, pRBCs do not express swine leukocyte antigens [17].…”