Background Serum amyloid A is an acute phase protein generated by hepatocytes through IL-6/IL-6R interaction. SAA is stable at baseline levels in the blood and accumulates abnormally under certain pathological situations such as systemic inflammation, acute tissue injury, chronic renal disease and infections. This study evaluated the use of SAA as a surrogate marker for graft rejection, inflammation and responses to anti-rejection drugs in a mouse model of skin allograft (SG).
Method Serum samples were collected at designated time points post skin grafting and immunosuppressant treatments. SAA2 titers were measured in an ELISA.
Results Normal mice showed low titers of serum amyloid A2 in sera (0.54+0.04 Μg /ml). This was also seen in sera from mMR16-1(Anti-IL-6R) treated mice without allografts (0.77+0.17 Μg /ml). SAA2 titers in sera of SG recipient mice increased by >100-fold at Day 1 Ptx (66.3+2.14 Μg /ml, P=6.79E-09 vs. normal sera), and then gradually returning to normal levels at Day 7 when the skin allografts were rejected (39.02+5.9, 42.75+15.31 and 3.7+0.08 Μg /ml at Days 2, 3, and 7, respectively). In contrast, SAA2 titers in sera from anti-IL6R treated mice remained at baseline levels (2.14+1.7, 0.8+0.1, 2.35+1.6 and 0.67+0.08 Μg /ml at Days 1, 2, 3 and 7, respectively), indicating SAA suppression by IL-6 inhibition. SG recipients treated with B-cell depleting anti-CD20 mAb exhibited high levels of SAA2 (20.96+7.91Μg/ml) while those treated with IVIG had moderately increased SAA2 (6.75+0.45 Μg/ml). The latter indicates IVIG also suppresses acute phase protein production in allograft rejection.
Conclusion SAA levels appear to be a sensitive indicator of alloimmunity activation and inflammation after SG. Treatment with anti-IL-6R completely inhibited SAA increases while IVIG also showed an effect. Measurement of SAA, in combination with other rejection/inflammation markers may have value in monitoring transplant recipients for inflammatory and immune activation events.
To cite this abstract in AMA style:Chai N, Wu G, Kim I, Klein A, Jordan S. Serum Amyloid A (SAA) Is a Sensitive Surrogate Marker for IL-6R Inhibition by Therapeutic Anti-IL6R Antibody: A Study in a Mouse Model of HLA Sensitization [abstract]. Am J Transplant. 2013; 13 (suppl 5). https://atcmeetingabstracts.com/abstract/serum-amyloid-a-saa-is-a-sensitive-surrogate-marker-for-il-6r-inhibition-by-therapeutic-anti-il6r-antibody-a-study-in-a-mouse-model-of-hla-sensitization/. Accessed November 30, 2020.
« Back to 2013 American Transplant Congress