Donor-specific antibodies to class II antigens are associated with accelerated cardiac allograft vasculopathy: a three-dimensional volumetric intravascular ultrasound study

Abstract

Background: Although a link between donor-specific antibodies against human leukocyte antigens type II (DSA II+) and transplant glomerulopathy has been clearly established, its role in cardiac allograft vasculopathy (CAV) is unclear.

Methods: Donor-specific antibodies were evaluated using solid-phase single-antigen bead assay before transplantation in 51 heart transplant recipients. Coronary angiography and three-dimensional intravascular ultrasound were performed at baseline and approximately 1 year after the baseline examination.

Results: There were 4 (7.8 %), 11 (21.5%), and 2 (3.9%) patients who had DSA against donor class I (DSA I+), DSA II+, or both, respectively. All patients had negative complement-dependent cytotoxic crossmatch. There was accelerated progression of CAV in the DSA II+ group demonstrated by accelerated progression in plaque index (plaque volume/vessel volume) compared to patients with no DSA II+ antibodies (13.8% [12%] vs. -7.9% [37%], P=0.01). The development of any angiographic CAV was also more common in DSA II+ patients as compared to the DSA- patients at 4 years (100% [0%] vs. 64.2% [10%], P=0.05). All other traditional risk factors for CAV or immunosuppression were similar between the groups (P>0.2 for all).

Conclusions: This is the first preliminary study demonstrating that heart transplant recipients with preformed class II DSA may be at an increased risk for accelerated CAV as detected by consecutive volumetric three-dimensional intravascular ultrasound.

Figure 1. The methods for conducting 3-dimensional intravascular ultrasound (IVUS) examinations and definition of IVUS measurements

IVUS was performed during routine coronary angiography with mechanical pullback (0.5 mm/s) from the mid to distal left anterior descending coronary artery to the left main coronary artery. The vessel length (VL), which was interrogated for each examination, was measured (A). The semiautomated contour software detected both the blood-media interface defined as lumen area (LA) and the media-adventitia interface defined as vessel area (VA). Plaque area (PA) was defined as the difference between VA and LA for each 2-dimensional image (B). Border detection was corrected manually in all frames after automatic border detection. Two-dimensional interrogations were performed at intervals of either 16 or 32 frames, depending on the heterogeneity of the image (C). Next, the vessel volume (VV), lumen volume (LV), and plaque volume (PV; mm³) were calculated with the Simpson rule for volumetric measurement and corrected for the segment length (mm³/mm). Plaque index (PI) was calculated as follows: PI=(PV/VV)×100%.

Figure 2. Relative changes in vessel volume, plaque volume and plaque index progression between the baseline and second IVUS examination in patients with and without DSA II+

a) The graph presents relative changes (in percent) in vessel volume (a), plaque volume (b) and plaque index (c) (plaque volume/vessel volume) between the baseline IVUS examination performed during the first year after transplant and the second IVUS exam performed a year afterwards in patients with DSA II+ compared to patients with no DSA pre transplant. There is a trend for accelerated vessel constriction and plaque progression, and a significant acceleration in plaque index progression with pre transplant donor specific antibodies against HLA class II antigens Results are represented by box plots (middle hash of the box indicates the median; 25th to 75th percentiles are represented by end caps of the box; whiskers extend to the last observed value still within 1.5 times the interquartile range [difference between the 25th and 75th percentiles] above or below the 25th and 75th percentiles). Results of the paired t test comparing baseline and the second IVUS exam performed a year afterwards are represented by P above each box plot. Results of the t test comparing between both groups are represented by p in the right lower corner.