Changes of Immunoglobulin and Complement Fragments in Liver Tissue at the Time of Pre-reperfusion and Post-reperfusion.

Feng changyin, Zheng zhiyong

(Department of Pathology, Dongfang Hospitial, Fuzhou, Fujian, China. 350025)

Objective: To study IgG, IgM, IgA, C3c, C4d, C1q changes pre-reperfusion and post-reperfusion in donors’ liver and its impact on liver rejection after transplantation.

Methods: 87 liver biopsy specimens were obtained from the donors and recipients at the time of transplantation from May 2007 to December 2008. The median age at transplantation was 26 years (range 26–71) including 26 male and 3 female. All recipients were hepatitis B infectious, 15 cases with liver cancer, one case with acute liver failure, one with sub-acute liver failure, and the rest with chronic hepatitis B and decompensated liver cirrhosis. All donors with 8 Hepatitis B virus-infected were dead with traumatic brain injury. The median age of all donors was 29 years (range 25–30 years). Each liver specimen have at least six portal area. Specimens of recipients were obtained from the subcapsular region without hepatocellular carcinoma. Specimens of donors were obtained from the subcapsular region. 20 specimens with moderate chronic hepatitis B were obtained as control group. All biopsy specimens were 10% phosphate-buffered formalin fixed and paraffin embedded for light microscopy. Immunohistochemical staining using the peroxidase method was carried out on each for IgG、IgM、IgA，the C3、C4d, C1q components of complement, HBsAg and HBcAg. Some specimens were stained with PAS and PASM. Optical microscope was used to observe the deposition of immunoglobulin and complement fragments in the liver. Scoring of  staining is based on the percentage of stained tissue on IHC that has a linear, circumferential staining pattern in both vascular walls of portal area(PV) and hepatic sinusoidal walls(HS): negative for 0, ＜25% for 1, 26 ~ 50% for 2,  > 50% for 3. All recipients were followed up for six months for post-transplantation rejection.

Results: The deposition of IgG, IgM, IgA, C1q statistically significant increased in both vascular walls of portal area and hepatic sinusoidal walls of donors’ livers(all p＜0.05). And the volume of increased were not associated with their deposition in recipients’ liver(all p>0.05). The donors’ liver with hepatitis B-negative (n=21) had higher HS IgG (p = 0.044) and PV C4d (p= 0.02) than the positive group (n=8) before reperfusion, while their rejection rates post-transplantation were not significant difference (23.8% and 25% respectively, p = 0.647). Recipients older than 50 years(n=13) had higher HS IgM(p=0.012), HS IgA（P=0.015）and PV IgG（P=0.012）than the other recipients(n=16) after reperfusion. The rejection rates were 30.77% and 18.75% respectively which were not significant difference (p = 0.374). Female recipients (3 cases) had higher HS C4d(p=0.001)and HS C1q（P=0.026）than male recipients after reperfusion. The rejection rates were 33.33% and 23.08%, which were not significant difference (P = 0.579). The rejection rate of group with mild organ preservation injury (n=23) was not higher than the moderate organ preservation injury group(30.43% and 0% respectively, p = 0.157). We performed Logit multivariate analyses to determine the impact of IgG, IgM, IgA, C3c, C4d, C1q on post-transplantation rejection. A significant predictor of rejection were pre-reperfusion HS IgA (odds ratio [OR] = 2.184; P = 0.11), ΔPV IgG(odds ratio [OR] = 4.05; P = 0.039).

Conclusions: The immunoglobulin and complement fragments depositing in donors’ liver are different in different gender and different age groups. The HBV infected donors’ livers have no effect on post-transplantation. Pre-reperfusion HS IgA andΔPV IgG are risk factors of rejection.