Table 6. C4d immunolabeling patterns, detection methods and association with rejection in ABO compatible liver transplants reported in the literature.
| Description of C4d deposition pattern | Contemporaneous DSA class I / II | Pretransplant LXM | Number C4d positive biopsies/ biopsies tested | Method of C4d detection | Anti-C4d antibody | Reference |
|---|---|---|---|---|---|---|
| Along portal tract capillaries, periportal ‘sinus’ | No | Yes | 5/5 AR (only 1 positive LXM) | IH | poly | (53) |
| Along portal tract capillaries, periportal ‘sinus’, the ‘vicinity’ of small blood vessels in portal tracts | No | No | 1/2 AR | IH | poly | (30) |
| ‘Equivocal’ | I+/II− | Yes | 0/1AR | n.s. | (54) | |
| Along portal tract capillaries, endothelium of portal vein and artery. Sinusoids and central vein did not stain | No | No | 11/22 AR; 0/13 negative for AR | IH. IF on positive IH samples. Paraffin embedded. | poly | (32) |
| Portal vein and artery, plus sinusoids only in moderate-severe AR | No | No | n.s./ 35 biopsies in 20 LRLT. (ABO donor-recipient compatibility not reported) | IH | n.s. | (55) |
| Along endothelium of portal veins, arteries, and capillaries. No sinusoidal or central vein deposits | No | No | 23/34 AR; 4/34 HCV; 2/29 controls. | IH. IF on positive IH samples. Paraffin embedded. | poly | (19) |
| ‘Vascular walls’ of portal areas. Sinusoids | No | No | 9/13 AR; 0/1 AR; 1/3 HBV recurrence; 4/14 HBV–native liver. | IH | poly | (35) |
| Hepatocytes only. The endothelium did not stain | No | No | AR: 5/5. HCV:0/5 | IH | poly | (56) |
| Endothelium of portal veins, arteries. Sinusoids | No | No | 2/25 AR; 1/1 Hyperacute; 1/6 CR (ductopenic); 1/8 CR (vascular); 0/7 negative for rejection; 0/6 native liver | IH | poly | (45) |
| Sinusoids. Central vein endothelium | I+/II− | Yes | 2/2 biopsies in 1 patient with pure AMR | IF on frozen tissue | mono | (21) |
| Portal stroma, portal vascular endothelium, portal capillaries, perivenular, or sinusoids. Diffuse if staining ≥50% portal tracts | No | Yes | 9/11 (positive LXM) 28/86 (negative LXM) | IH | poly | (20) |
| Sinusoids. Diffuse if staining of > 50% sinusoidal cells. (Portal tract staining not reported) | No | No | 36 biopsies/34 patients; 3/9 AR, 2/2 CR, 0/5 HCV; 2/14 normal; 1/4 other | IF on frozen tissue | n.s. | (46) |
| ‘Small portal vessels’ | I−/II+ | No | 1/1 AR+HR | n.s. | n.s. | (23) |
| Diffuse deposits in portal venules, arteries, sinusoids | I+/II+ | No | 1/1 Acute ductopenic rejection | IH | poly | (22) |
| Portal venular plexus, sinusoids | No | Yes | 2/16 AR; 3/13 CR; 3/27 Protocol bx; 1/10 PNF; 2/14 CLN; 3/11 BO. | IH | mono | (57) |
| Portal stroma, portal vessels, central veins. Sinusoids | No | Yes | 7 / 7 CR (1 positive preTx LXM) | IF on frozen tissue | mono | (29) |
| ‘Portal triad’ | I+/II+ | Yes | 1/1 AR, combined liver/kidney transplant recipient | IF | poly | (24) |
| Pattern not specified | I+/II+ | Yes | 1/1 AR (LXM+); n.p. / 1AR (LXM+) | IH | n.s. | (25) |
| Portal stroma, portal endothelium | No | Yes | 23/27 XM+ (3 ABO incompatible) | IH | poly | (31) |
LXM = lymphocytotoxic crossmatch; Ab = antibodies; Poly = polyclonal ab; mono = monoclonal ab; AR = acute rejection; CR = chronic rejection; HR = humoral rejection; LRLT = living related liver transplants; IH = immunohistochemistry; IF = immunofluorescence; PNF = primary nonfunction; CLN = centrilobular necrosis; BDO = biliary obstruction; bx = biopsy; Tx = transplant; n.s. = not specified; n.p. = not performed.