Abstract
Purpose Serum amyloid A (SAA) is one of the acute phase proteins generated by hepatocytes through IL-6 stimulation. This study evaluated the usefulness of measuring SAA as a surrogate marker to monitor IL-6R blockage using anti-IL6R antibody in a mouse model of allosensitization. Methods and Materials A mouse model of allosensitization involving a C57BL/6 mouse recipient of a skin graft (SG) from HLA.A2 transgenic mouse was employed. The SG recipients were divided into different treatment groups, receiving anti-IL6R, anti-CD20, IVIG and control antibodies, respectively. Serum samples were collected at designated time points post skin grafting and 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). 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 after skin allograft rejection (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 blockage. 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 SAA. Conclusions We conclude that SAA titers globally reflect status of allograft rejection, inflammation and treatment responses to IL-6 receptor blockage and immune modulation by IVIG, but not B-cell depletion by anti-CD20. Measurement of SAA, in combination with other rejection/inflammation markers may have value in monitoring transplant patients.
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