Transfusion-related inhibition of cytokines (TRICK). Experimental transfer of neutralizing autoantibodies to interleukin-6 by plasma transfusions.

BACKGROUND: For some unknown reason humans may 'spontaneously' produce high amounts of neutralizing autoantibodies to a number of growth factors and cytokines. Reaching a certain high level the antibodies render the person cytokine deficient, mostly without overt clinical manifestations. The autoantibodies in question are detectable in normal immunoglobulin preparations and correspondingly in normal human plasma for transfusion. High affinity neutralizing autoantibodies to interleukin-6 (aAb-IL-6) are present in high titres in 0.1% of plasma from blood donors. Using aAb-IL-6 as a model we here report the first study addressing transfer of cytokine autoantibodies with blood components. MATERIALS AND METHODS: We transferred high amounts of aAb-IL-6 to two patients suffering from end-stage disease of multiple myeloma. This was done by serial transfusions with normal human plasma highly positive for aAb-IL-6. We assessed recovery and kinetics of the transferred aAb-IL-6 and exposed how the recipients' plasma IL-6 bound to aAb-IL-6. RESULTS: Free IL-6 was detectable in plasma of the recipients before transfusion. After the first transfusion IL-6 became immune complexed to aAb-IL-6 the molar plasma concentrations of which exceeded total IL-6 at least 500 times. CONCLUSION: The observations signify that high amounts of neutralizing autoantibodies to cytokines (in this context aAb-IL-6) are occasionally transferred by transfusion. Although neither beneficial nor obvious detrimental effects of the plasmas were observed in this study our measurements evidently uncover a hitherto unknown form of transfusion-related immune modulation: transfusion-related inhibition of cytokines (TRICK). Depending on the cytokine autoantibody in question, the phenomenon might affect immune responses to infection and recovery after stem cell transplantation.