Background. There is no known serum marker for intestinal rejection. Serum
concentrations of the amino acid citrulline arise almost exclusively from t
he intestinal mucosa. We examined the impact of acute cellular rejection (A
CR) of intestinal allografts on serum citrulline levels.
Methods. Citrulline concentrations were assayed in serum samples of healthy
volunteers (n=6) and seven patients who underwent small bowel transplants
(SBTx). Trends in mean citrulline concentrations versus degree of ACR were
assessed by matching posttransplantation citrulline concentrations with pat
ients' grade of ACR at time of serum collection. Rejection was confirmed by
biopsy and graded by following standardized criteria. An additional patien
t had citrulline concentrations determined for 31 sequential specimens 3-60
days posttransplant.
Results. Mean citrulline concentrations in controls were significantly high
er than posttransplantation samples at any rejection grade. Mean concentrat
ions declined significantly as rejection severity increased. The overall do
wnward trend was statistically significant (P<0.05). In sequential measurem
ents, citrulline levels increased significantly over time with declining se
verity of rejection. The increase in mean citrulline concentration between
posttransplant days 3-16 and 52-60 was significant (P<0.01).
Conclusions. Serum citrulline levels decline with increasing grade of ACR a
nd may be a useful serum marker for intestinal rejection.