Soluble HLA Class I and Class II Concentrations in Factor VIII and PCC Preparations

Abstract

Soluble HLA class 1 (sHLA-CI) and class II (sHLA-CII) molecules were quantitated in 11 commercially available factor VIII and prothrombin complex concentrate (PCC) preparations by enzyme-linked immunosorbent assays (ELISA). In 4 preparations, we detected traces of sHLA-CI (0.01-0.07 mg/l), and in 7 hemostatic preparations small amounts of sHLA-CII molecules (0.02-0.28 mg/l). The concentrations of these contaminant molecules are unequivocally below the mean values of sHLA in human plasma (sHLA-CI: 1.01±0.72 mg/l; sHLA-CII: 1.53±2.44 mg/l). Based on the total amount of chronically administered factor VIII or PCC, contaminating sHLA molecules may be in principle able to exert immunomodulatory effects in patients treated with such preparations.

In vitro immunosuppressive activity of soluble HLA class I and Fas ligand molecules:do they play a role in autologous blood transfusion?

“…1) Molecules of sHLA‐I, sHLA‐I‐HC, β 2 m, sHLA‐II, and sFasL have been detected in supernatants of stored autologous blood components; 2) the concentrations of sHLA‐I, sHLA‐I‐HC, sHLA‐II, and sFasL were higher in RBCs than in WBC‐reduced RBCs, FFP, and serum, whereas the levels of β 2 m were comparable in all blood components; 3) the amount of sHLA‐I and sFasL molecules in RBCs correlated with the length of blood storage; 4) supernatants of autologous RBCs exerted immunomodu‐latory effects in vitro, such as the inhibition of CTC activity and MLR and the induction of apoptosis; and 5) the in vitro immunomodulatory effects are attributable to the presence of functional sHLA‐I and/or sFasL molecules. Our findings are also in agreement with published literature data indicating that functional, soluble molecules are detectable in other blood derivatives such as albumin, immunoglobulin, and clotting factor preparations 22–25 …”

“…HLA class II antigens are expressed on antigen‐presenting cells and on activated T cells and are present in serum as soluble molecules (sHLA‐II) 21 . Large amounts of sHLA‐I and sHLA‐II molecules have been detected in commercial albumin, immunoglobulin, and hemostatic preparations 22–25 . In vitro studies indicate that soluble HLA molecules may modulate immunocompetent cell function in at least three ways: 1) sHLA‐I molecules may bind their physiologic ligands and inhibit T‐cell function by receptor blockade 26 ; 2) sHLA‐I and sHLA‐II molecules can be phagocytosed by antigen‐presenting cells, degraded to peptides, and presented to CD4+ T cells in the context of membrane HLA class II antigens, a process known as indirect presentation and which may lead to either immune tolerance or activation 27 ; and 3) sHLA‐I may induce soluble Fas ligand (FasL) expression and secretion in activated CD8+ T cells and induce their apoptosis 28–32 .…”

Association of soluble HLA‐G plasma levels with HLA‐G alleles

“…The plasma concentrations of sHLA class I (sHLA‐I) molecules were measured by ELISA as described (21). Recombinant HLA‐B7 molecules (22) served as a standard to calculate the total amount of sHLA‐I antigens. The determination of sHLA‐G plasma levels was performed by a two‐step ELISA as previously described (20).…”