Session Time: 3:15pm-4:45pm
Presentation Time: 3:51pm-4:03pm
*Purpose: Detection of antibody (Ab) against angiotensin-II receptor (AT1R) following VAD implantation portends poorer outcomes for heart transplantation (HT). However, the cause of this sensitization is unknown. Since we found that soluble receptor (sAT1R) is released during kidney inflammation, we speculated that VAD implantation might induce release of sAT1R which leads to Ab formation.
*Methods: Serum was collected monthly from 45 VAD recipients who subsequently underwent HT. Ab and sAT1R were tested pre-VAD, 1 and 3 months post-VAD and pre-HT by elisa (One Lambda, Cusabio) with positivity defined as >11 U/ml and >20 pg/ml, respectively. Cytokines were tested by elisa (R&D Systems) with positivity defined as values exceeding the normal range described by manufacturer.
*Results: Elevated sAT1R was prevalent among pre-VAD patients (69%) and remained stable (p=ns) at all post-VAD time points (61%, 73%, 72%). sAT1R concentrations (pg/ml) were also equivalent (p=ns) pre-VAD (82±99) and all timepoints thereafter (80±83, 80±83, 85±46). In contrast, the frequency of AT1R+Ab+ patients was low pre-VAD (22%) but increased to 70% and 62% (p<0.05) by 1 M and 3 M post-VAD. Prevalence declined by pre-HT but remained higher than pre-VAD (48%, p<0.05). Pre-VAD Ab concentrations were low (9±9 U/ml) but increased by 1 M and 3 M post-VAD (17±13 , 45±74, p<0.05) and remained elevated pre-HT (24±26 U/ml, p<0.05)). In contrast, 90% of sAT1R negative patients lacked Ab at all time points. A panel of inflammatory cytokines tested on AT1R+Ab- patients pre-VAD showed most with elevated IL6, IL10 and/or TGFb but normal IL1b and IL2.
Pre-VAD AT1R+Ab- patients were then divided into those who became Ab+ post-VAD vs. those remaining Ab-. Testing the same cytokine panel showed the frequency of cytokines was similar between Ab+ and Ab- groups with one exception (Table). Patients with elevated IL10 post-VAD were more likely to produce Ab than patients with normal IL10.
*Conclusions: We show that elevated sAT1R is common prior to VAD placement and unaffected post-VAD. This suggests sAT1R may be released during tissue injury such as heart failure but is insufficiently antigenic to result in Ab formation. Assessment of select cytokines showed most patients produced inflammatory cytokines pre-VAD. However, only patients with elevated IL10 post-VAD produced Ab. We speculate that elevations in IL10 during and after VAD placement promotes sAT1R antigenicity or B cell responsiveness which leads to Ab formation in the post-VAD period.
To cite this abstract in AMA style:Kimball P, Chau V, McDougan F, Flattery M, Shah K. Possible Mechanism of Sensitization against Angiotensin Type II Receptor after LVAD Implantation [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/possible-mechanism-of-sensitization-against-angiotensin-type-ii-receptor-after-lvad-implantation/. Accessed December 4, 2020.
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