Lack of C1q Reactivity in Post-Lvad Patient Sera

End stage heart disease can be treated with implantation of a mechanical circulatory support device, often to assist the left ventricle (LVAD) as a bridge to heart transplantation. During the LVAD operation patients may be exposed to large volumes of blood and blood products resulting in production of anti-HLA antibodies (Abs). This higher degree of HLA sensitization results in positive virtual crossmatches, eliminating many potential donors. However, when LVAD patients are transplanted they do not have a different rejection severity or frequency or poorer graft outcome than non-LVAD or non-sensitized heart transplant recipients. We hypothesized that while these LVAD treated patients display anti-HLA Abs these Abs may not be C1q reactive and therefore may not be functionally deleterious. We evaluated 90 patients (61 male, 29 female, mean age of 54 years). Seventy-three patient sera were evaluated pre-LVAD and 17 patient sera post-LVAD for the presence of cI and cII HLA Abs and C1q reactivity using One Lambda, Inc. reagents and following manufacturers instructions. The cI and cII PRAs pre and post LVAD were divided into three groups. For cI PRAs of 0-5% were seen in 57% of patients pre-LVAD vs. 59% of patients post-LVAD. PRAs of > 5-50% were seen in 23% of patients pre-LVAD vs. 29% of patients post-LVAD. Finally, PRAs of > 50% were seen in 20% of patients pre-LVAD vs. 12% of patients post-LVAD. Class II PRAs of 0-5% were seen in 83% of patients pre-LVAD vs. 59% of patients post-LVAD. Class II PRAs of > 5-50% were seen in 7% of patients pre-LVAD vs. 29% of patients post-LVAD (p≤0.05). Finally, PRAs of >50% were seen in 10% of patients pre-LVAD vs. 12% of patients post-LVAD. Pre-LVAD C1q reactivity was seen in 38% of patients with cI HLA Abs and 45% of patients with cII HLA Abs. However, in contradistinction to the pre-LVAD C1q positive reactivity only 8% of both cI and/or cII post-LVAD sera were C1q positive (8% vs. 38%, p<0.01; 8% vs. 45%, p<0.01) These data suggest that while HLA antibodies are present in post-LVAD patient sera 92% of these antibodies tested as C1q non-reactive. This may explain why these identifiable HLA antibodies do not adversely impact LVAD treated heart transplant patients.