Acute antibody-mediated rejection after intestinal transplantation

Table 1 Donor and recipient demographic and clinical characteristics

Characteristic	Transplants (n = 175)
Donor characteristics
Age (yr)	25.4 ± 9.9
Gender (% male)	77.7
Nonwhite race (%)	16.6
Cold ischemic time (h)	7.6 ± 1.5
Recipient characteristics
Age at transplantation (yr)	43.0 ± 12.5
Gender (% male)	38.9
Nonwhite race (%)	5.9
Primary diagnoses, n (%)
Vascular occlusion	59 (33.7)
Crohn’s disease	34 (19.4)
Neoplastic disorders	28 (16.0)
Motility disorders	21 (12.0)
Others	33 (18.9)
Donor/recipient sex mismatches (%)	56.6
Donor CMV positive/recipient negative (%)	21.9
Type of graft liver-free/liver-inclusive (%)	61.1/38.9
Two mismatches in HLA loci A/B/DR (%)	39.1/82.1/66.9
PRA at transplantation (≥ 10%) Class I (%)	40
Class II (%)	26.3
Positive T/B cell cross-match (%)	25.7
Preformed DSA (%)	30.3
Retransplantation (%)	6.7
Induction, n (%)
None	41 (23.4)
Zenapax	3 (1.7)
Thymoglobulin	7 (4.0)
Campath-1H	124 (70.9)
Follow-up (mo; range)	37.5 ± 22.7 (0.7 to 81.5)

CMV: Cytomegalovirus; PRA: Panel reactive antibody; HLA: Human leukocyte antigens; DSA: Donor-specific antibody.

Table 2 Characteristics of 18 patients with diagnosis of acute antibody-medicated rejection

Case	Tx type	POD (d)	XM		DSA at time of Tx and/or rejection	De novo DSA	Vascular alterations	C4d	#ACR ≤360 d
			T-cell	B-cell
1	MV + K	4	1:32	1:16	A1, A25, B8, B18	DR51	++	Focal	0
2	SB	5	1:256	1:512	B7, B44, BW4, DQ1, DR10	DR15, DR51	+++	Diffuse	2
3	SB	5	1:2	1:2	B60	DR16	++	Diffuse	3
41	SB	6	1:8	1:8	B35, B60	A31, DQ7, DR11	+++	Diffuse	0
		109			A24, B604	DR14, DR52	++	Diffuse
5	SB	7	Neg	1:1	A3, B18, DR17	None	++	Diffuse	0
6	MV	7	Neg	1:8	A26, B70, DR52	None	++	Diffuse	1
7	MMV	9	1:32	1:8	A2	None	+++	Diffuse	4
8	SB	10	Neg	Neg	DR52	None	++	Diffuse	1
9	MMV	10	1:2	1:2	B13, BW4, DR7, DR53	DQ1	++	Diffuse	2
101	SB + K	11	Neg	1:4	A32, B8	A1, DR17	++	Diffuse	4
		52			A32, DQ44		++	Diffuse
11	SB + P	14	Neg	1:4	A3, B64	DQ7	++	Diffuse	0
121	SB	15	Neg	Neg	A2, B50	DQ8, DR53, DR4	+	Diffuse	5
		112			B7, B504		+	Focal
13	SB	41	1:256	1:8	A3, BW4, B53	DR18	+++	Diffuse	2
14	MMV	84	1:4	1:1	A25, B14, B18	None	++	Diffuse	1
15	SB	140	Neg	Neg	A24	A28, B78, A30, DQ7, 9	+	Diffuse	1
16	SB	162	1:2	1:2	A24, B444	DQ1, CW5	++	Diffuse	2
172	SB	4	Neg	Neg	A28, B78, A30, DQ7, 9	B44, B58, DR4	+++	Diffuse	2
183	MMV	18	1:1	1:8	A11, B7, DR12, DR17, DQ2	None	++	Diffuse	1

Type of transplant: SB: An isolated small bowel; MMV: A modified multivisceral graft; MV: A full multivisceral graft; P: Pancreas; K: Kidney.

¹Patients with repeat ABMR;

²Patient with a history of ABMR after prior transplant;

³Patient with prior transplant;

⁴DSA detected at time of rejection. POD: ABMR days post-transplant; XM: Cross-match; DSA: Donor-specific antibody; ACR: Acute cellular rejection.

Table 3 Treatment and outcome of 18 patients with acute antibody-mediated rejection

Case	Treatment	Graft status/survival (mo)	Re-Tx/graft type	Patient status/survival (mo)
1	ST/IVIG/OKT3	CHR/30.5	None	Dead (liver failure)/30.5
2	ST/IVIG/OKT3/Campath	CHR/13.5	None	Dead (ruptured pseudo-aneurysm)/18.6
3	ST/OKT3	Functioning/75.9	None	Alive/75.9
41	ST/OKT3	CHR/5.4	Yes/MV	Dead (pneumonia)/43.0
5	ST/OKT3	Functioning/17.7	None	Alive/17.7
6	ST/OKT3	Functioning/56.4	None	Alive/56.4
7	ST/OKT3/Campath	ACR/31.7	None	Dead (pneumonia)/31.7
8	ST/Campath	Functioning/30.3	None	Dead (unknown)/30.3
9	ST	CHR/35.4	Yes/MV	Alive/55.4
101	ST/OKT3	ACR/13.2	None	Dead (sepsis)/15.5
11	ST	Functioning/52.6	None	Alive/52.6
121	ST/ATG	CHR/22.6	None	Alive/22.6
13	ST	AHR/2.7	Yes/MV	Alive/76.4
14	ST	Functioning/22.5	None	Alive/22.5
15	ST/OKT3	CHR/4.8	None	Dead (sepsis)/32.8
16	ST	CHR/12.3	None	Alive/46.2
172	ST/OKT3	CHR/12.6	Yes/SB	Dead (GI bleeding)/13.3
183	ST/OKT3	Functioning/37.6	Yes/MV	Alive/37.6

Type of transplant: SB: An isolated small bowel; MV: A full multivisceral graft.

¹Patients with repeat ABMR;

²Patient with a history of ABMR after prior transplant;

³Patient with prior transplant. ST: Steroids; IVIG: Intravenous immunoglobulin; ACR: Acute cellular rejection; CHR: Chronic rejection.

Table 4 Pretransplant risk factors for acute antibody-mediated rejection (univariate analysis)

Variables	Non-ABMR (n = 157)	ABMR (n = 18)	OR	95%CI	P
Donor age (yr)	25.6 ± 10.2	24.0 ± 6.5	0.98	0.93-1.04	0.549
Female donor, n (%)	33 (20.8)	6 (37.5)	0.44	0.15-1.29	0.133
Cold ischemic time (h)	7.72 ± 1.52	7.58 ± 1.11	0.94	0.66-1.33	0.711
Recipient age	43.7 ± 12.4	36.9 ± 12.0	0.96	0.92-0.99	0.028
Female recipient, n (%)	94 (59.8)	13 (72.2)	0.57	0.19-1.69	0.299
Donor CMV positive/recipient negative, n (%)	34 (21.4)	4 (25.0)	1.12	0.69-1.81	0.642
Donor/recipient sex mismatches, n (%)	88 (55.3)	11 (68.7)	1.78	0.59-5.35	0.308
HLA mismatches ≥ 4, n (%)	107 (67.3)	12 (75.0)	1.46	0.45-4.74	0.531
Prior transplant, n (%)	9 (5.7)	2 (12.5)	2.38	0.47-2.12	0.296
Campath-1H induction, n (%)	113 (71.1)	12 (75.0)	0.72	0.30-1.73	0.468
Liver-free graft, n (%)	92 (58.5)	15 (83.3)	3.53	1.08-12.7	0.031
Presence of spleen, n (%)	99 (63.1)	15 (83.3)	2.93	0.81-10.55	0.071
Anti-HLA antibodies
Positive CDC-XM, n (%)	30 (19.1)	14 (77.8)	21.17	5.76-77.81	< 0.0001
PRA I ≥ 10%, n (%)	53 (33.8)	18 (100)	33.36	4.32-257.52	< 0.0001
PRA II ≥ 10%, n (%)	32 (20.4)	14 (77.8)	13.67	4.21-44.36	< 0.0001
Presence of DSA, n (%)	37 (23.6)	18 (100)	55.14	7.09-428.38	< 0.0001

ABMR: Antibody-mediated rejection; CMV: Cytomegalovirus; CDC-XM: Complement-dependent lymphocytotoxic cross-match; PRA: Panel reactive antibody; DSA: Donor-specific antibody.

Table 5 Pretransplant risk factors for acute antibody-mediated rejection (multivariate analysis)

Variables	OR	95%CI	P
Liver-free graft	8.791	2.011-38.480	0.004
PRA class I	16.302	3.092-85.801	0.001
PRA class II	6.023	1.490-24.253	0.012

PRA: Panel reactive antibody.