- Email: [email protected]
Monoclonal antibodies raised against human tumor cells
356
A n n , ~ l . ~ A C H T M e e a n g , 1981
DETECTION O~ HLA-C LOC'~$ "BLANKS" IffARTIGLOBULIICYIOTOXICXrY. J . C . Burroughs. and T.C F u l l e r , OepC. o f S u r g e r y , Harvard H e d i c a l School a t t h e H a s s a c h ' ~ e t t s General H o s p i t a l , Boston. I t a p p e a r s that a l a r g e p r o p o r t i o n o f BLA-C l o c u s a l l e l e s a r e undefzned ( ' b ~ a n k s ' ) a n d / o r may b e t r u l y s s l e n t , amorphzc d e t e r m i n a n t s . On t h e c o n t r a r y , from o u r s t u d x e s , i t a p p e a r s t h a t f a l s e n e g a t i v e a s s l s n m e n t s o f a t ] e a s t some o f t h e r e c o p i z e ~ s p e c i f x c x t l e s (IELA-Ct~2,3,S,6) o c c u r f r e q u e n t l y and a r e a c c o u n t e d f c r on t h e b a s i s o f I o m a n d v a r x a b l e expressxon o f e h e s e d e t e r m z n a n t s on t h e c( I I s u r f a c e . The IILA-C pbenotypes o f a 29 member, H L k - s e l e c t u n r e l a t e d p. he1 were d e t e r a x n e d wzth a l l 7E~ and gWS I n t ( r n a t x o n a l r e a g e n t s u s i n g N H c y t o t o x i c i t y ( N - C l ) C ) . Using • s e l e c t b a t t e r y o f t h e most r e h a b l e i ~ s e r a mad a d d s t l o r ~ l BLA-C l o c u s s e r a ( & a e r a / e a c h Cvi -& e n t x g e n , 2 e a c h f o r CwS,6), t h e pa~uel was r e t y p e d i n p a r a l l e l by N-CDC and antsglobulsa (AG) CDC (goa: ~ hu K serua), Of 14 N-Cl)~ (Cw-,-) c e l l s . 4 had a s i n g l e , and 3 had b o t h NLA-C a l l e l e s d e t e c t a b l e by AG. Of 12 N-CDC (Cwl-6, o) c e i l s , S were found t o have • s e c o ~ I d e f l n s b l e a l l e l e by AG. The r e s p e c t z v e s e r a f o r e a c h s p e c s f l c i t y , when r e a c t i v e b y e s t h e r t e c b n z q u e , were c o n c o r d a n t and s t r o n g l y c y t o t o x i c ; no u n d e r l y i n g a n t i b o d y d i r e c t e d . toward t h e IILA-B assocxmted • U e l e s ( e g . B w ~ - C ~ ) was e v i d e n t (v~z. 3 B~t,A~ Cw5° c e l l s were n e g a t i v e f o r ( ~ by AG). TmmilF s t u d i e s a l s o suppor~ t h e s e d a t a ( v l z . a deigned C • l l e l e o ~ a n i n h e r l t a b l e h e p l o t y p e ~ e ~ a t l v e by N-Cl)C zn a n o f f s p n n g , p o s z t i v e by AG). Thus, t h e low c e l l s u r f a c e phenotyp~e e x p r e s s z o n o f ~LA-C s u p p o r t s ~he d i r e c t e v i d e n c e f o r weak /emunogen~czty o f BLA°C so p l a n n e d zmmmxz~tlon s t u d i e s ( F e r r a r a e t •1o, J. lmmmol. 12._~: 731, '7B) and would s u l ~ e s t t h a t t h e c u m u l a t i v e &erie f r e q u e n c y o f t h e p r e s e n t l y r e c o p l z e d HLA-C • l l e l e s i s u n d e r e s t ~ u t e d .
FREQLI.:;CY A~;D PANEL REACTXVITIE5 OF TR~SPLA,'~TCA,NDIDA1£ SEAAPOSITIVE BY A~TIGLOBM,IN BU1 NE~AfXVL BY STA~ARDCRO$S,~ATCHINGo P,H. Chauvenet~ S.A. Anderson and l~.)~.Bajiow~k£, D i v i s i o n of Vrolo~y, Cniversity'of-Texa-s-HeaL~-gcle~e . . . . Center ,lc S~n ~ntonio, San Antonio. Texas
Since October of 1978 we ha~: crossmatched aer• from 100 renal tra~eplant candidates by Johneon a n t l g l o b u l i n and Amoa-modified ~IH c y t o t o x t c i t y methods. A l l available sera fro~each patient were t e s t e d i n d u p l i c a t e ( a t a e r u m d i l u t l o n s 3 : 1 ; 1~1; 1 : 2 ; 1:4 and 1:8) a g a i n s t e n r i c h e d T-lymoh~cyte~ from a t o t a l o f 72 p o s s i b l e c a d a t e r l c and 28 l l v i n g r e l a t e d donors. Of t h e 3105 t o t a l l y m p h o c y t e ° s e r ~ c o m b i n a t i o n s t e s t e d , 77 c r o s s . a r c h e s (71 d i f f e r e n t s e r a from 24 • n d i v l d u a l s ) were by t h e ~ t a ~ d a r d crossm~tch ne~.~tlve, but scronAly p o s i t i v e by a n t l g l o b u l i n , ~ o f t h e s e 71 a n t i g l o b u l l n p o s i t i v e ~era were n e i t h e r t h e most h i g h l y r e a c t i v e ( s g a l n s t a 60 member s e l e c t p a n e l ) n o r t h e most c u r r e n t p a t i e n t ~ e r u ~ s a ~ p I ° Panel r e a c t l v l t l e s of 52 c f t h e a n t l g l o b u l l n p o s i t i v e s e r a ( a s determined by Amos-modlfsed NXH c y t o t o x l c i t y ) were i n f a c t . below 40~. A t o t a l o f 19 p o s s i b l e t r a n s p l a n t s were c o n t r a i n d i c a t e d s o : e l y on t h e b a s i s o f a p o s i t i v e a n t l g l o b u l i n c r o s e m a t c h . T~o o f t h e s ~ 19 p a t i e n t s had p r e v i o u s l y r e j e c t e d c a d • r e t i e r e n a l t r a n s p l a n t s , and a l l 19 had r e c e i v e d m u l t i p l e t r a n s f u s i o n s . ~ased on o u r e x p e r l e n ~ , we a d v o c a t e a cro~smatch p ~ o t o c o l which i n c l u d e s a n t l ~ I o b u l l n c r o s s -
matching o£ olaf available patient ser•.
I~ONOCLOHALAIITIBOOIES RAISED AGAINSTITtMAN7LIHCRCELLS. J.. Cicctare11.t, P . l . Terasak.t C ~ n d R. B i l l i n g . Tissue Typin~ Leboratory. UCLA Sc1~ool ~of Vedlctne~" " Un~verslt~-oF C a l i f o r n i a , Los Angeles, Ca:tfornta. Human tumor c e l l s were prepared from fresh s u r g i c a l l y resected specie mens by ~ass~ng through screens a~d tn some instances enzjp~e treatment, A s~ngle c e l l suspension of the t u , ~ r c e l l was isolated and used as an tmmunogen for the production of hybrldoma c e l l 1tries according to the technique of t411stetn. Isolated tumor c e l l s were also frozen f o r l a t e r use i n the
A.bs~c~s
357 cytotox~c assay of antibody produced by hybr~doma c e l l hnes. Using s i x tumor c e l l preparations as ~mmunogenswe have tested over 3,000 supernatants ~n which hybr~doma clones were growing These supernatants were tested using the o r i g i n a l tumor c e l l ~munogen as target c e l l s and ~ n ~ s t instances a panel of 10 T and B c e l l s . Of 3,000 supernatants tested approximately 90 have no detectable cytotox~c antibody of the 107 positive 50" appeared as ant~-lymphocyte ant;body or ant~-B cell antibody. The remaining cytotoxtr supernatants seem to be specific to components of the tumor c e l l ~mmuno~en preparation e~ther lymphocytes or tumor c e l l s . The best characterized hybridoma antibody reacts to le~o~yosarcoma c e l l s at a 1.64,000 t~ter from ascites f l u i d but does not react to autologous lymphocytes and ~s not absorbed ~ i t h non,a1 smooth muscle f~bers and c e l l s . Thus far one HLA-A3-All antibody is the only HLA-ABC antibody that has been produced by th~s procedure. ~o a l l o reactive DR antibodies ~ere found but many reactive to pan-DR were noted in the supernatants. ~e feel these results are encouraging for using mcrocytotoxlc~ty and hybr~doma technology for the production of antibodies sPec i f i c to human tumors
DRUG-INDUCED ANTIBODIkS: INTERACTION OF DRUGSWITH FOLYHORFHIC ~NBP~ANE D~TER~II~X~S ON P|~'IhLLTS AND NkUIROPH[LS. F . H . J . . C l a a s ~ J . Lan~erak. L.. Lolkes de Beer aod J . J ~ van Rood, Dept. Immunohaematology and Bloodbank, Unxversxty N e d i c a l C e n t e r , L e i d e n , ~'~l~'~ertands.
In t h e b e t a o f | 0 p a t t e n t s wxth drug-xnduced thrumbocytopenxa o r n e u t r o w c n i a , a n t i b o d i e s were found, which r e a c t e d i n t h e i n d i r e c t xu~nunofluoresceoce a s s a y w i t h donor p l a t e l e t s o r n e u t r o p h x l s o n l y when t h e s e c e l l s h~d been f i r s t e x posed t o t h e o f f e n d i n g d r u g . l~hen t h e s e s e r a were t e s t e d a g a i n s t a p a n e l o f o f d o n o r s , t h e a n t i b o d i e s showed r e s t r l c t l o n i n t h e s e n s e t h a t they were a b l e t o r e a c t w i t h t h e d r u g - e x p o s e d c e l l s o f o n l y p a r t of t h e d o n o r s , d e s p i t e t h e f a c t t h a t a l l donors could b l n d t h e d r u g . There was no c l e a r c u t a s s o c i a t i o n ~ I t h one o f t h e HLA-A. -B. -C o r -DR a n t i g e n s , t h e p l a t e l e t - s p e c i f i c a n t l g e o PL&l o r t h e n e u t r o p h z l - s p e c x f x c a n t i g e n s 9A, ~ I , NA2. NBI and ~IEl. However. t h e r e s t r i c t e d d e t e r m n a n t showed N e n d e h a n s e g r e g a t i o n xn f a m i l i e s a n d m o nozygotxc t w i n s , e a c t e d i d e n t i c a l l y w i t h t h e s e s e r a . The a b i l i t y of c e r t a l n d r u g s t o I n h i b i t t h e r e a c t i o n s o f a l l o - a n t l s e r a w i t h t h e i r s p e c i f i c a n t i g e n s was a l s o t e s t e d . I t was found t h a t T i c a r p e n ( T i c a r c i l l l n e - d z - s o d x u m ) was a b l e t o i n h i b i t t h e r e a c t i o n s o f a s e r t m a a g a l n s t a platelet-speclfic a n t i g e n (phenotype f r e q u e n c y ~ 50Z), whereas i t b a d g e i n f l u e n c e on t h e r e a ( t l o n s o f s e r a a g a i n s t t h e HLA-A. and -B a n t i g e n s , t h e n o n HLA antigens $A and 5B and the p l a t e l e t antigen PLAI. Thebe r e s u l t s I n d i c a t e t h a t c e r t a i n n o t e a r l i e r d e f i n e d polymorphxc n e u t r o p h i l o r p l a t e l e L - s p e c i f z c a n t i g e n s a r e i n v o l v e d xn t h e donor r e s t r i c t i o n . E i t h e r t h e drug i s r e c o g n i z e d i n c o m b l n a t i o n w i t h t h o s e a n t i g e n s , o r t h e d r u g changes t h e a n t i g e n s I n v o l v e d .
IILA-DR4AND PRIMARY BILIARY CIRRHOSIS. A NE~DISEASE ASSOCIATION. C.M. ConnOrSo K.B. M i l l ~ S i ~ e r s k v ~ M.N. Kaplan. and M.R. C a r o v ~ . Depts. o f Hed.. Brigham a-nd~-~~tal a~d Tufts-New England H e d l c a l C e n t e r . Boston. Ha. Primary B i ] t s ~ v C i r r h o s i s (PbC) i s a p r o g r e s s i v e , sometimes f a t a l l i v e r d i s e a s e a ~ s o c i a t e d w i t h a u t o . ~ n u n e phenomenon~ t e n d s t o o c c u r In f a m I H e ~ and I s most f r e q b e n t l y fovnd i n Caucasian females. The d i s e a s e i s o f t e n f i r s t d e t e c t e d by abnorma~ l i v e r c h e m i s t r i e s and i s c h a r a c t e r i z e d by b i l e s t a s l s due t o an i n f l a u ~ a ~ o r y r e a c t i o n around t h e b l l e d u c t s w l t h I n f i l t r a t l o n o f m c , o n u c l e a r and plasma c e l l s and ~ u t l m l t o c h o n d r i a l a n t i b o d y . T h l r t y - t w o c o n s e c u t i v e , uz~related p a t i e n t s w l t h PBC were HLAoA.B.C.DR t y p e d . Thes~ r e s u l t s were compared w i t h a l o c a l Caucasian p a n e l of t h l r t y - t h r e e u n r e l a t e d i n d i v i d u a l s and t h e t o t a l Caucasian p a n e l typed i n t h e 8 t h I n t e r n a t i o n a l Workshop. Although HLA-A,B,C a n t i g e n s were o b s e r v e d a s e x p e c t e d .
A n n , ~ l . ~ A C H T M e e a n g , 1981
DETECTION O~ HLA-C LOC'~$ "BLANKS" IffARTIGLOBULIICYIOTOXICXrY. J . C . Burroughs. and T.C F u l l e r , OepC. o f S u r g e r y , Harvard H e d i c a l School a t t h e H a s s a c h ' ~ e t t s General H o s p i t a l , Boston. I t a p p e a r s that a l a r g e p r o p o r t i o n o f BLA-C l o c u s a l l e l e s a r e undefzned ( ' b ~ a n k s ' ) a n d / o r may b e t r u l y s s l e n t , amorphzc d e t e r m i n a n t s . On t h e c o n t r a r y , from o u r s t u d x e s , i t a p p e a r s t h a t f a l s e n e g a t i v e a s s l s n m e n t s o f a t ] e a s t some o f t h e r e c o p i z e ~ s p e c i f x c x t l e s (IELA-Ct~2,3,S,6) o c c u r f r e q u e n t l y and a r e a c c o u n t e d f c r on t h e b a s i s o f I o m a n d v a r x a b l e expressxon o f e h e s e d e t e r m z n a n t s on t h e c( I I s u r f a c e . The IILA-C pbenotypes o f a 29 member, H L k - s e l e c t u n r e l a t e d p. he1 were d e t e r a x n e d wzth a l l 7E~ and gWS I n t ( r n a t x o n a l r e a g e n t s u s i n g N H c y t o t o x i c i t y ( N - C l ) C ) . Using • s e l e c t b a t t e r y o f t h e most r e h a b l e i ~ s e r a mad a d d s t l o r ~ l BLA-C l o c u s s e r a ( & a e r a / e a c h Cvi -& e n t x g e n , 2 e a c h f o r CwS,6), t h e pa~uel was r e t y p e d i n p a r a l l e l by N-CDC and antsglobulsa (AG) CDC (goa: ~ hu K serua), Of 14 N-Cl)~ (Cw-,-) c e l l s . 4 had a s i n g l e , and 3 had b o t h NLA-C a l l e l e s d e t e c t a b l e by AG. Of 12 N-CDC (Cwl-6, o) c e i l s , S were found t o have • s e c o ~ I d e f l n s b l e a l l e l e by AG. The r e s p e c t z v e s e r a f o r e a c h s p e c s f l c i t y , when r e a c t i v e b y e s t h e r t e c b n z q u e , were c o n c o r d a n t and s t r o n g l y c y t o t o x i c ; no u n d e r l y i n g a n t i b o d y d i r e c t e d . toward t h e IILA-B assocxmted • U e l e s ( e g . B w ~ - C ~ ) was e v i d e n t (v~z. 3 B~t,A~ Cw5° c e l l s were n e g a t i v e f o r ( ~ by AG). TmmilF s t u d i e s a l s o suppor~ t h e s e d a t a ( v l z . a deigned C • l l e l e o ~ a n i n h e r l t a b l e h e p l o t y p e ~ e ~ a t l v e by N-Cl)C zn a n o f f s p n n g , p o s z t i v e by AG). Thus, t h e low c e l l s u r f a c e phenotyp~e e x p r e s s z o n o f ~LA-C s u p p o r t s ~he d i r e c t e v i d e n c e f o r weak /emunogen~czty o f BLA°C so p l a n n e d zmmmxz~tlon s t u d i e s ( F e r r a r a e t •1o, J. lmmmol. 12._~: 731, '7B) and would s u l ~ e s t t h a t t h e c u m u l a t i v e &erie f r e q u e n c y o f t h e p r e s e n t l y r e c o p l z e d HLA-C • l l e l e s i s u n d e r e s t ~ u t e d .
FREQLI.:;CY A~;D PANEL REACTXVITIE5 OF TR~SPLA,'~TCA,NDIDA1£ SEAAPOSITIVE BY A~TIGLOBM,IN BU1 NE~AfXVL BY STA~ARDCRO$S,~ATCHINGo P,H. Chauvenet~ S.A. Anderson and l~.)~.Bajiow~k£, D i v i s i o n of Vrolo~y, Cniversity'of-Texa-s-HeaL~-gcle~e . . . . Center ,lc S~n ~ntonio, San Antonio. Texas
Since October of 1978 we ha~: crossmatched aer• from 100 renal tra~eplant candidates by Johneon a n t l g l o b u l i n and Amoa-modified ~IH c y t o t o x t c i t y methods. A l l available sera fro~each patient were t e s t e d i n d u p l i c a t e ( a t a e r u m d i l u t l o n s 3 : 1 ; 1~1; 1 : 2 ; 1:4 and 1:8) a g a i n s t e n r i c h e d T-lymoh~cyte~ from a t o t a l o f 72 p o s s i b l e c a d a t e r l c and 28 l l v i n g r e l a t e d donors. Of t h e 3105 t o t a l l y m p h o c y t e ° s e r ~ c o m b i n a t i o n s t e s t e d , 77 c r o s s . a r c h e s (71 d i f f e r e n t s e r a from 24 • n d i v l d u a l s ) were by t h e ~ t a ~ d a r d crossm~tch ne~.~tlve, but scronAly p o s i t i v e by a n t l g l o b u l i n , ~ o f t h e s e 71 a n t i g l o b u l l n p o s i t i v e ~era were n e i t h e r t h e most h i g h l y r e a c t i v e ( s g a l n s t a 60 member s e l e c t p a n e l ) n o r t h e most c u r r e n t p a t i e n t ~ e r u ~ s a ~ p I ° Panel r e a c t l v l t l e s of 52 c f t h e a n t l g l o b u l l n p o s i t i v e s e r a ( a s determined by Amos-modlfsed NXH c y t o t o x l c i t y ) were i n f a c t . below 40~. A t o t a l o f 19 p o s s i b l e t r a n s p l a n t s were c o n t r a i n d i c a t e d s o : e l y on t h e b a s i s o f a p o s i t i v e a n t l g l o b u l i n c r o s e m a t c h . T~o o f t h e s ~ 19 p a t i e n t s had p r e v i o u s l y r e j e c t e d c a d • r e t i e r e n a l t r a n s p l a n t s , and a l l 19 had r e c e i v e d m u l t i p l e t r a n s f u s i o n s . ~ased on o u r e x p e r l e n ~ , we a d v o c a t e a cro~smatch p ~ o t o c o l which i n c l u d e s a n t l ~ I o b u l l n c r o s s -
matching o£ olaf available patient ser•.
I~ONOCLOHALAIITIBOOIES RAISED AGAINSTITtMAN7LIHCRCELLS. J.. Cicctare11.t, P . l . Terasak.t C ~ n d R. B i l l i n g . Tissue Typin~ Leboratory. UCLA Sc1~ool ~of Vedlctne~" " Un~verslt~-oF C a l i f o r n i a , Los Angeles, Ca:tfornta. Human tumor c e l l s were prepared from fresh s u r g i c a l l y resected specie mens by ~ass~ng through screens a~d tn some instances enzjp~e treatment, A s~ngle c e l l suspension of the t u , ~ r c e l l was isolated and used as an tmmunogen for the production of hybrldoma c e l l 1tries according to the technique of t411stetn. Isolated tumor c e l l s were also frozen f o r l a t e r use i n the
A.bs~c~s
357 cytotox~c assay of antibody produced by hybr~doma c e l l hnes. Using s i x tumor c e l l preparations as ~mmunogenswe have tested over 3,000 supernatants ~n which hybr~doma clones were growing These supernatants were tested using the o r i g i n a l tumor c e l l ~munogen as target c e l l s and ~ n ~ s t instances a panel of 10 T and B c e l l s . Of 3,000 supernatants tested approximately 90 have no detectable cytotox~c antibody of the 107 positive 50" appeared as ant~-lymphocyte ant;body or ant~-B cell antibody. The remaining cytotoxtr supernatants seem to be specific to components of the tumor c e l l ~mmuno~en preparation e~ther lymphocytes or tumor c e l l s . The best characterized hybridoma antibody reacts to le~o~yosarcoma c e l l s at a 1.64,000 t~ter from ascites f l u i d but does not react to autologous lymphocytes and ~s not absorbed ~ i t h non,a1 smooth muscle f~bers and c e l l s . Thus far one HLA-A3-All antibody is the only HLA-ABC antibody that has been produced by th~s procedure. ~o a l l o reactive DR antibodies ~ere found but many reactive to pan-DR were noted in the supernatants. ~e feel these results are encouraging for using mcrocytotoxlc~ty and hybr~doma technology for the production of antibodies sPec i f i c to human tumors
DRUG-INDUCED ANTIBODIkS: INTERACTION OF DRUGSWITH FOLYHORFHIC ~NBP~ANE D~TER~II~X~S ON P|~'IhLLTS AND NkUIROPH[LS. F . H . J . . C l a a s ~ J . Lan~erak. L.. Lolkes de Beer aod J . J ~ van Rood, Dept. Immunohaematology and Bloodbank, Unxversxty N e d i c a l C e n t e r , L e i d e n , ~'~l~'~ertands.
In t h e b e t a o f | 0 p a t t e n t s wxth drug-xnduced thrumbocytopenxa o r n e u t r o w c n i a , a n t i b o d i e s were found, which r e a c t e d i n t h e i n d i r e c t xu~nunofluoresceoce a s s a y w i t h donor p l a t e l e t s o r n e u t r o p h x l s o n l y when t h e s e c e l l s h~d been f i r s t e x posed t o t h e o f f e n d i n g d r u g . l~hen t h e s e s e r a were t e s t e d a g a i n s t a p a n e l o f o f d o n o r s , t h e a n t i b o d i e s showed r e s t r l c t l o n i n t h e s e n s e t h a t they were a b l e t o r e a c t w i t h t h e d r u g - e x p o s e d c e l l s o f o n l y p a r t of t h e d o n o r s , d e s p i t e t h e f a c t t h a t a l l donors could b l n d t h e d r u g . There was no c l e a r c u t a s s o c i a t i o n ~ I t h one o f t h e HLA-A. -B. -C o r -DR a n t i g e n s , t h e p l a t e l e t - s p e c i f i c a n t l g e o PL&l o r t h e n e u t r o p h z l - s p e c x f x c a n t i g e n s 9A, ~ I , NA2. NBI and ~IEl. However. t h e r e s t r i c t e d d e t e r m n a n t showed N e n d e h a n s e g r e g a t i o n xn f a m i l i e s a n d m o nozygotxc t w i n s , e a c t e d i d e n t i c a l l y w i t h t h e s e s e r a . The a b i l i t y of c e r t a l n d r u g s t o I n h i b i t t h e r e a c t i o n s o f a l l o - a n t l s e r a w i t h t h e i r s p e c i f i c a n t i g e n s was a l s o t e s t e d . I t was found t h a t T i c a r p e n ( T i c a r c i l l l n e - d z - s o d x u m ) was a b l e t o i n h i b i t t h e r e a c t i o n s o f a s e r t m a a g a l n s t a platelet-speclfic a n t i g e n (phenotype f r e q u e n c y ~ 50Z), whereas i t b a d g e i n f l u e n c e on t h e r e a ( t l o n s o f s e r a a g a i n s t t h e HLA-A. and -B a n t i g e n s , t h e n o n HLA antigens $A and 5B and the p l a t e l e t antigen PLAI. Thebe r e s u l t s I n d i c a t e t h a t c e r t a i n n o t e a r l i e r d e f i n e d polymorphxc n e u t r o p h i l o r p l a t e l e L - s p e c i f z c a n t i g e n s a r e i n v o l v e d xn t h e donor r e s t r i c t i o n . E i t h e r t h e drug i s r e c o g n i z e d i n c o m b l n a t i o n w i t h t h o s e a n t i g e n s , o r t h e d r u g changes t h e a n t i g e n s I n v o l v e d .
IILA-DR4AND PRIMARY BILIARY CIRRHOSIS. A NE~DISEASE ASSOCIATION. C.M. ConnOrSo K.B. M i l l ~ S i ~ e r s k v ~ M.N. Kaplan. and M.R. C a r o v ~ . Depts. o f Hed.. Brigham a-nd~-~~tal a~d Tufts-New England H e d l c a l C e n t e r . Boston. Ha. Primary B i ] t s ~ v C i r r h o s i s (PbC) i s a p r o g r e s s i v e , sometimes f a t a l l i v e r d i s e a s e a ~ s o c i a t e d w i t h a u t o . ~ n u n e phenomenon~ t e n d s t o o c c u r In f a m I H e ~ and I s most f r e q b e n t l y fovnd i n Caucasian females. The d i s e a s e i s o f t e n f i r s t d e t e c t e d by abnorma~ l i v e r c h e m i s t r i e s and i s c h a r a c t e r i z e d by b i l e s t a s l s due t o an i n f l a u ~ a ~ o r y r e a c t i o n around t h e b l l e d u c t s w l t h I n f i l t r a t l o n o f m c , o n u c l e a r and plasma c e l l s and ~ u t l m l t o c h o n d r i a l a n t i b o d y . T h l r t y - t w o c o n s e c u t i v e , uz~related p a t i e n t s w l t h PBC were HLAoA.B.C.DR t y p e d . Thes~ r e s u l t s were compared w i t h a l o c a l Caucasian p a n e l of t h l r t y - t h r e e u n r e l a t e d i n d i v i d u a l s and t h e t o t a l Caucasian p a n e l typed i n t h e 8 t h I n t e r n a t i o n a l Workshop. Although HLA-A,B,C a n t i g e n s were o b s e r v e d a s e x p e c t e d .