Bethell, D

Corman, J

Fiala, JM

Ishikawa, M

Iwatsuki, S

Johansen, TS

Kashiwagi, N

Starzl, TE

English

PubMed

D-Scholarship@Pitt

---"--------~-~-~~--,," ·'-'·_--:'··"-"'''''1 SURGICAL FORU,,! , e plates were gently rinsed of non-"e then examined by inverted phase ts scored on the basis of the number ?er 150 X microscopic field. >ULTS posttransplant nephrectomy showed · donor kidney cells, but also against ,-A antigens. For example, patient 8 ~ed by a graft (HL-A2, 10;12, W 17) \2, 11;5, 12), (HL-Al, 2;8, 18), [L-A 9, 10; W5, WI5); but not to or (HL-A 11, W32;W5, X). This was consistent with the specificity of his skin reactions to purified HL-A while in the midst of a rejection epi-ria. The degree of specilk reactivity icnts posttransplant nephrectomy or, 'he reactions of peripheral leukocytes ive depletion of cells directed against · example, patient 2 (HL-A2, 28,17, lining (HL-A2, 28;14, 27) was un-Jd toward targets bearing (HL-AI, , the phenotypes (I-IL-A 2, W32; 8, ). Similarly patient 4 (HL-A 9, 11; · with (HL-A 2, 11 ;W5, W15) de-10;W5, W15) and (HL-Al, 30;14, 11;W5, WI5), (HL-A 2, W32; 8, ldom intervals during the first month reacted toward donor cells in vitro, nce of clinical rejection for 60 days. actions toward donor targets at four I clinical evidence of rejection, based eta, and nuclide scanning. Patient 1 d from donor with (HL-A 3, 9;7, 8) 1 tested at 25 days post transplant; ;; reacted to donor cells and to targets I, but not to those bearing (HL-A 2, 5, WI5). Five days later clinical signs (HL-A 2, 28;17, 18) engrafted with ) (HL-A 1, 30;14, X), (HL-A 2, 5, \VI5) but not (HL-A 11, X;W5, ORGAN TRANSPLANTATION 345 W15) four days prior to the onset of a rejection episode. All of the patients \vho displayed positive reactions underwent transplant rejec-tion. On the other hand, rejection was never observed within six days of a negative reaction. DISCUSSION The results reported here have compelling implications for the im-munodiagnosis of transplant rejection. The test may distinguish patients with circulating immunoreactive cells prior to clinical evidence of re-jection. This method reflects modifications of the techniques reported earlier by Govaerts, by Wolf et aI, and by Quadracci et aI, as noted earlier (1). The advantages of the present method, which are reflected in its enhanced sensitivity in the detection of cellular immunity, in-clude (a) the small number of requisite target cells, (b) the relatively short incubation period, (c) its simplicity and flexibility, and (d) its apparent dependence on antigen recognition rather than on cellular de-struction. Further experience with the method will ascertain whether its immunodiagnostic efficiency warrants intensified immunosuppressive treatment for rejection solely on this basis and without any clinical evi-dence of graft destruction. REFERENCES 1. Kahan BD, Reisfeld RA: Transplantation Antigens. Academic Press, 1972, pp 507 2. Kahan BD, Mittal KK, Reisfeld RA, et al: Surgery (in press) MIXED LYMPHOCYTE CULTURE AND GRAFT REJECTION NOBORU KAsHIWAGI, MD, JACQUES CORMAN, MD, SHUNZABURO IWATSUKI, MD, MAKOTO ISHIKAWA, MD, JEAN MARC FIALA, MD, TORBEN S. JOHANSEN, MD, DELIA BETHELL, MS, AND THOMAS E. STARZL, MD, PHD, FACS HL-A TYPING has proved to be a poor predictor of kidney compati-bility (1). It has been claimed that genes determining mixed lympho-cyte culture (MLC) are apart from those of HL-A (2). Considering Frum the Department of Surgery, University of Colorado l"vfedicaI Center alld the Denver VA Hospital. Supported by research grants from the Veterans Ad-ministration and by ""Tational Institutes of Health grallts AI-A!H-08898, Ai\{-07772, RR-0005J and RR-00069. , . •. ~I ~: 346 SuRGICAL FORUM cellular processes in the induction phase of rejection mechanism, MLC would seem to be a logical tool for donor selection. METHODS MLC was studied in 42 patients with kidney and 9 patients with liver transplantation. Kidney recipients were divided into primary related (19 patients), primary unrelated (14 patients) and secondary or mul-tiple unrelated transplants (9 patients). None of the first two groups, but all of the last group were under immunosuppression at the time of MLC. Follow-up studies are for one to nirie months after transplanta-tion, excluding no patients. Rejection was diagnosed pathologically and by positive findings on two consecutive days of three clinical lab-oratory tests (blood urea nitrogen, creatinine clearance, and urine sodium concentration for kidney; serum bilirubin, transaminases, and alkaline phosphatase for liver). MLC was performed by Bach's method (3) with modifications. Stimulation index (SI) of MLC was defined by the ratio between the reaction of recipient cells to mitomycin-C-treated donor cells and that to mitomycin-C-treated recipient cells. A Sllower than 10 was considered compatible; those with SI higher than 10 were designated incompatible. RESUL TS AND CONCLUSIONS The results (Table 1) indicated a positive although imperfect corre-lation between one-way MLC and the clinical course after primary kid-ney transplantation, either related or unrelated. A good MLC match was much more common than good HL-A matching. Similar findings have been reported by other authors (4,5), although they have used two-way MLC. Except for the double haplotype identical sibling cases, there was no correlation between HL-A and MLC. Even among these sibling cases there were two patients who rejected kidneys despite an identical HL-A and MLC. This finding and the report of Seigler and associates (6) suggests the possibility that minor incompatibilities may have been responsible. Immunosuppressive therapy apparently affected the MLC results, and the potential ability of the recipient to reject the graft was not adequately expressed by the MLC (Table 1). With liver transplantation, there has not yet been a correlation between out-come and MLC. REFERENCES 1. Halgrimson CG, Rapaport FT, Terasaki PI, et at: Net histocompatibility ratios (NHR) for clinical transplantation. Transplant Proc 3:140-148, 1971 2. Yunis EJ, Seigler RL, et al: HL-A typing, mixed leukocyte reactivity, and skin graft survival in a family with a combinant at the HL-l chromosomal re-gion. Transplantation 15:435-440, 1973 3. Bach FH, Voynow NK: One-way stimulation in mixed leukocyte cultures. Science 153:545-547, 1966 ORGAN TRANSPLANTATION z _ 0 t:: f:: ~ :::! '" ..., '" j.C) (J] p<: < 0 U z 00 00 ., .::: 0;:: oS ... 0 >. ., r:: "Cl ~ "<tt--;>.0\0 8 \0 S l ·c 0..0 0.- ~d "Cl B "" 'V p:: ON ..... N t-- N 00 ........ /\V ., .:::: oS , .., 0 >. 0,) r:: "Cl ~ >." ;:; " S " ... ; 0.- v "Cl <' B -"" 'V... r:: ;:J C o o SURGICAL FORU:-"l ORGAN TRANSPLANTATION 347 e of rejection mechanism, MLC v.; £ 0 lOr selection. U M 00 \0 Z ~ o\N i ~ r-- oq c<) 0 It) M c<) ci S "" ~ ~ S 0 ""':r-; -a kidney and 9 patients with liver i III \0 0\ D 0 0 N ;'::0 u e divided into primary related z ..... ~ -< .§ ~ ,atients) and secondary or mul- I . None of the first two groups, en ~ '""* ~ Z 0 ro munosuppression at the time of .... ~ III -< 00 0 ..... 00 .... ..... eJ) , nine months after transplanta- ~ 2l a '" was diagnosed pathologically .S utive days of three clinical lab-en "d reatinine clearance, and urine ~ f-! £ !l. '" 00 0- 00 .... - ~ <0 n bilirubin, transaminases, and ~ ...l 0 0 as performed by Bach's method '" '" ~ OJ dex (S1) of MLC was detined $:! Z .... 0) C) :I: 0 Co? ... 'ecipient cells to mitomycin-C- '- t: E::: '" <II ..... >. I..l ~ g '" .::: ~ o-.:r '" cin-C-treated recipient cells. A 'U .:::: 00 0:1 000 MM >. ...... en ..., -.... "d 0) 'U f.:.J w: ~ .... Co? k2 c ltible; those with S1 higher than ~ cn ~ "d <: 0 Co? >. :;;; .... u Z >. u 0) d ..... ~ <:::s '" c .... .... c "d 0:1 '" C,) \ii "d ~ :; ]. :9 'eLUSIONS ~ ~ t-"<:::s U >.": ~ c ~ co\o ro ~ c" sitive although imperfect corre- l:! ::; .... \0 .... -<i .... <:::s c:l \0 8 ~ 0 f-< c<) .8 !inical course after primary kid- \.) "" S ~ .;:: ~ >. ~ .... :; 0 .... " mrelated. A good MLC match .....) III ·c 0 \1:)'" p.. \f) M ro Mt- ~ O\\f) "d 1 p.. • • "d M N "d NO o\N 0:1 C) ~o c c.a L-A matching. Similar findings Z "' ..... 0) ..... 0 N .... < '" -;0 u .- ~ 4,5), although they have used ~ "d 0) 0) • u -. <) .... r/J "g", aplotype identical sibling cases, ~ ~ t:I "d ro4-< 0 0) 0 ..0 '" -;0 C Q ~ and MLC. Even among these ~ f-< * Q; E til 'ho rejected kidneys despite an 15 ~ ON 00 ... o c<) 0- E; c ~ III 0 o u ~ and the report of Seigler and t< Q U Q '" '" .0 !at minor incompatibilities may "::= t1) - ... ..... '" ;ive therapy apparently affected .5 ~ en '" ity of the recipient to reject the "d ..... Ii: fii ...... M 00 OM 0 ..... Ks~ y the MLC (Table 1) . With < 0 '" .... p: ... ;.:: OJ) leen a correlation between out- 0 D-D~ .... 0 ro~ "dO) :t: Z 0)'<:: !:: 0 .- ~ "d'M ES ~ f:: ..... ~ ..... c<) o 0 U t-N '" ...... J:: Q (I} OJ d PI, et al: Net hi,tocompatibility III ..., ::: § (I} III 'ransplant Proc 3:140-148. 1971 6 ~ '" ..... -ng, mixed leukocyte reactivity, and C :::> .!:! .D nant at the HL-l chromosomal rc- ~ ~= Vl 00 00 00 00 p.. ro U ~ ..... ...... ...... ............ ~ J\V J\V J\V /\V * ..... 0:1 ,lation in mixed leukocyte cultures. ;:;< .s 348 SURGICAL FORUM 4. Bach JF, Debray-Sachs M, et al: Correlation between mixed lymphocyte culture performed before renal transplantation and kidney function. Clin Exp Immuno! 6:821-827, 1970 5. Cochrum KC, Perkins HA, Payne RO, et al: The correlation of MLC with graft survival. Transplant Proc 5:391-396, 1973 6. Seigler HF, (lllnneEs JC, Robinson RR, et al: Renal transplantation be-tween HL-A identical donor-recipient pairs. J Clin Invest 15:3200-3215, 1972 RECOVERY FROM HEPATORENAL SYNDROME AFTER SUCCESSFUL ORTHOTOPIC LIVER TRANSPLANTATION SHUNZABURO IWATSUKI, MD, JACQUES CORMAN, MD, MORDECAI POPOVTZER, MD, MAKOTO ISHIKAWA, MD, AND THOMAS E. STARZL, MD, PHD, FACS IN ASMUCH AS THE KID!\EY failure of the hepatorenal syndrome (1) is believed to be secondary to hepatic dysfunction, replacement of the diseased liver should improve renal function. This objective was real-ized in three patients with the hepatorenal syndrome treated by ortho-topic liver transplantation. CASE MATERIAL The patients, who were 34, 42, and 44 yr old, suffered from cirrhosis. They had massive ascites and edema and two of them were in stage III or IV coma. All had had normal renal function documented within a few weeks of transplantation, but progressive renal failure had then supervened \vith azotemia and oliguria. Two patients had a preopera-tive urine sodium concentration of less than 1 mEq/liter, while in case 3 it was 40 mEq/liter. The degree of combined renal and hepatic fail-ure can be seen in Table 1. RESULTS Hepatic function in all three patients steadily improved after liver replacement (Table 1), but the course of recovery of kidney function varied. In cases 1 and 3 the characteristic urine findings, including From the Departments of Surgery and Medicine, University of Colorado Medical Center and the Deliver V A Hospital. Supported by the Veterans Ad-ministration, National Institutes of Health grants AI-AM-08898 and AM-Olll2, and Division 01 Research Resources grants RR-0005J and RR-00069. ORGAN TRANSPLANTATION 

Mixed lymphocyte culture and graft rejection.

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Mixed lymphocyte culture and graft rejection

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Mixed lymphocyte culture and graft rejection.

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