Elevated serum HLA class I levels coincide with acute and chronic graft-versus-host disease

Abstract

Summary:More than two decades ago, the presence of naturally occurring soluble HLA class I molecules (sHLA-I) in the The ability to predict the likely occurrence of graftsera of healthy individuals was reported by van Rood et al 2 versus-host-disease (GVHD) after BMT would be and Charlton and Zmijewski. 3 Both groups defined these extremely valuable. We performed a retrospective study sHLA-I molecules by inhibition of HLA-specific alloantion the correlation between soluble HLA class I (sHLAsera in a complement-dependent cytotoxicity assay. sHLA-I) levels and GVHD in the sera of 34 patients receiving I can be detected in virtually all body fluids. 4 Serum HLA an allogeneic BMT and in the sera of 12 patients receivlevels are fairly constant in normal individuals and range ing an autologous BMT. sHLA-I levels measured prebetween 0.5 and 25 g/ml. 5-9 and at different times post-BMT were correlated with Different lines of evidence suggest that sHLA-I is the occurrence of post-BMT complications, ie acute increased during immunologically active periods, eg during graft-versus-host disease (aGVHD), chronic graft-verthe course of viral infections, 9-11 after vaccination 12 and sus-host disease (cGVHD), infections and relapse. No during rejection episodes. [13][14][15][16][17][18] The liver is a major source changes in sHLA-I levels (⌬sHLA-I) occurred in autoof sHLA-I as has been shown in liver transplant recipients, logous and allogeneic BMT patients without GVHD. In where up to 50% of the total sHLA-I found in the recipient contrast, sHLA-I reached high levels in patients sufferafter transplantation is of donor-type. 17 Analysis of the ing from GVHD. Increased sHLA-I levels correlated post-transplantation period revealed a correlation between strongly with episodes of both acute and chronic GVHD increased levels of both donor-type serum sHLA-I and total (P = 0.004 and P = 0.005, respectively). Also during serum sHLA-I with rejection episodes. 13,14 In kidney and relapse increased sHLA-I levels were found (P = 0.032).heart transplant recipients increased sHLA-I levels are also During infections sHLA-I levels increased, although not correlated with rejection episodes. [15][16][17][18] In kidney transplant significantly. Kinetic studies gave no evidence that the recipients, however, this correlation is still controversial. 19 increase in sHLA-I levels preceded the clinical occursHLA-I levels have also been analyzed in recipients of rence of aGVHD or of cGVHD. A slight, but significant BMT. Tsuji et al 20 and Westhoff et al 21 were the first to correlation was found between total blood bilirubin levnote an increase of sHLA-I levels coinciding with the cliniels and sHLA-I levels in patients suffering from GVHD cal signs of GVHD in a small series of patients. The effect (P = 0.037), indicating the contribution of the liver as a of infections on sHLA-I levels, however, were not investisource of sHLA-I. We conclude that measurements of gated. Recently, Puppo et al 22 reported their results on sHLA-I levels do not function as a...

Soluble human leucocyte antigen-G molecules in peripheral blood haematopoietic stem cell transplantation: a specific role to prevent acute graft-versus-host disease and a link with regulatory T cells

“…In the first month after allotransplantation, a high sHLA class I level was found associated with aGVHD occurrence. Liem et al have already reported an increase of sHLA class I levels in bone marrow transplanted patients correlated with episodes of both acute and chronic GVHD [28]. This higher level of sHLA class I could be due to the release of sHLA class I molecules by damaged cells during aGVHD.…”

“…However, 43% of those w/o aGVHD patients developed a chronic GVHD later (data not shown). Liem et al have already reported an increase of sHLA class I levels in bone marrow transplanted patients correlated with episodes of both acute and chronic GVHD [28]. Soluble HLA-G molecules are also involved in immune suppression and play a role in allograft acceptance.…”

Inhibition of Epstein–Barr virus (EBV)-specific CD8+ cytotoxic T lymphocyte (CTL) activity by soluble HLA class Iin vitro

“…sHLA class I molecules are present in human sera and in the supernatant of lymphocyte cultures [3]. Their level is markedly increased in the sera of patients after bone marrow or organ transplantation in association with graft‐ versus ‐host disorders or episodes of rejection [4–6]. It is also increased in viral infections, autoimmune disorders and cancer [7–9].…”

Levels of soluble HLA-I and β2M in patients with acute myeloid leukemia and advanced myelodysplastic syndrome: association with clinical behavior and outcome of induction therapy

“…AML and MDS were classified according to the French-American-British (FAB) system. 13,26 Antecedent hematologic disease (AHD) was defined as a documented abnormality in the blood count present for at least 1 month before presentation. One month is defined before presenting to MD Anderson Cancer Center, irrespective of whether therapy was initiated immediately or after the waiting period.…”

“…8 A recent study indicates that b2M, in addition to karyotype, may be a valuable prognostic marker in myelodysplastic syndrome (MDS). 9 After the discovery of free circulating HLA-I (sHLA-I) in serum, 10,11 it has been shown that these levels are increased in patients with evidence of cellular destruction, such as those with autoimmune diseases, 12 graft versus-host disease, [13][14][15] acute transplant rejection, 16 viral infection 17 and proliferating tumors. 18 In vitro data indicate that increased expression of surface HLA-I on tumor cells enhances their susceptibility to the cytolytic activity of T cells.…”