kell-cellano blood group system

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Nov. 25 , 1950 THERMAL COAGULABILITY O F SERUM PROTEINS lioHn^ 1203 Clifton (1949) compared t h e results h e obtained using three " cancer tests "-namely, a n antiproteolytic reaction a nd thermal coagulation tests. Using the iodoacetate test, he found n o significant difference in results whether t he original technique o f Huggins e t a l . o r their later modifica- tion w a s applied. These results a r e shown i n summarized form i n Table I . In h i s entire series (235 cases) the overall accuracy in cancer diagnosis was only 55.5%. Bodansky a n d Mclnnes (1950) found t h e original tech. nique recommended b y Huggins e t al . unreliable a nd adopted their o wn modification of t he second method described. Their results a r e summarized i n Table I. Homburger e t a l . (1950) published a n account o f their investigations a n d included a detailed list o f cases. They used both techniques described by Huggins e t al., and, a s w e have done, made a n attempt t o assess t h e reliability a n d reproducibility o f t he test. Theycondemn the original method of Huggins e t al., maintaining that reproduction o f t h e test b y different investigators i s impossible. They con- sider t he modified method easier t o reproduce a n d less com- plicated, b u t find t h e results obtained a t considerable variance with those from t he former method (Table I ) . Finally, Kiefer e t a l . (1950) carried o u t t h e modified technique o f Huggins e t a l . o n 7 00 apparently healthy m e n and women. Al l except si x gave values higher than 9.3. These latter were found t o give figures greater than 9 o n repetition. O f 2 5 cancer cases ru n as controls, 7 6 % gave a positive test. According t these workers " t h e thermal coagulation end-point i s striking a n d reproducible," a n d " i n no instance id multiple determinations o f t he end-point upon t h e same specimen vary more than o n e tube." T he results o f t h e si x groups of investigators clearly show n o consistent correlation, s o that t h e conclusion i s inevit- able that t h e test a s such i s valueless. T he figures obtained b y Cliffton (1949), Homburger e t a l . (1950), a n d ourselves, al l using t h e original technique, a r e directly comparable, a n d contrast sharply with t h e results quoted b y Huggins e t a l. (Table I ) I W e h a d hoped that t h e test might have some application i n t h e diagnosis o f malignant disease i n t h e chest o r abdomen. In o ur experience, however, strongly positive tests were nearly always obtained in acute a nd chronic inflammatory lesions o f th e chest a nd in haemorrhagic states in t h e alimentary tract n o t associated with malig- nancy (Table II). T h e conclusion, therefore, i s that h e change in serum proteins manifest altered thermal coagulability is n o t invariably present with malignant disease, even in clinically advanced lesions, a n d also occurs i n a high proportion o f cases with non-malignant pathology a nd even i n apparently healthy individuals. Th e cause o f such a change i s n o t necessarily related to an alteration i n t h e total serum pro- teins. T h e nature o f t h e change i s a s y e t Summary T h e thermal coagulability o f serum proteins i n th e presence o f iodoacetic acid h a s been examined i n 6 5 normal indi- viduals, 8 9 cases of malignant disease, and 6 3 patients with other diseases. A n "iodoacetate index " h as been calculated f o r each serum; this h a s been used to assess changes i n t h e coagulability o f serum proteins i n relation t o disease. T h e distribution pattern o f th e figures s o obtained leads t o t h e conclusion that t h e determination o f such a n index i s useless i n t h e diagnosis o f malignant disease. No t only m a y serum from apparently healthy individuals furnish iodoacetate figures falling into t h e index range suggested f o r cancer cases, a n d vice versa, b u t most cases of non-malignant disease gave vahies i n t h e " cancer range." Th e test also reveals no consistent correlation between "iodoacetate index " a n d t h e severity o f t h e malignant condi- tion; even advanced cases o f cancer m a y give figures i n the "normal range." REFERENCES Bodansky, O . , and McInnes, G . F . (1950). Cancer, 3, 1 . Cliffton, E . E . (1949). J. nat. Cancer Inst., 1 0 , 719. Homburger, F . , Pfeiffer, P . H . , Page, O., Rizzone, G . P . , a n d Benotti, J . (1950). Cancer, 3 , 1 5 . Huggins, C . , Miller, G . M . , a n d Jensen, E. V. (1949). Cancer Res., 9 , 177. Kiefer, . , Sullivan, B. H., an d Littlefield, W. (1950). Proc. Soc. exp. Biol., N.Y., 7 3 , 2 9 . KELL-CELLANO BLOOD GROUP SYSTEM I N PREGNANCY A ND TRANSFUSION BY B . COCHRANE, M.B., M.R.C.O.G. (From Nottingham City Hospital) R . H. MALONE, M.D., D.P.H. AND L . DUNSFORD (Fromn t h e Sheffield Blood Transfusion Centre) Coombs, Mourant, a n d Race (1946) described a n e w antigen-antibody system (Kell) unrelated t o t h e R h system b u t nevertheless capable o f producing haemolytic disease o f t he newborn. More recently, Levine e t a l . (1949) found another antibody (Cellano) which also caused haemolytic disease o f t h e newborn, a n d showed that t h e Kell a n d Cellano genes a re alleles. They suggested that t h e symbols K a n d , previously employed t o represent Kell-positive and Kell-negative, be used t o indicate t he presence o f t h e Kell a nd Cellano genes respectively, and calculated that t he three genotypes, K K , K k , a n d k k occur with frequencies o f 0.2%, 8.6%, a n d 91.2% respectively among white Americans. S i x examples of anti-Kell a r e noted i n their paper a n d a t least a dozen others a re known at t h e present time ( R . R . Race-personal communication). T h e Kell antibody i n t h e case described here w a s discovered a t t he Sheffield Blood Transfusion Centre i n 1948 (Dunsford, 1949), a n d i s exceptional i n reacting i n saline b u t n o t in human serum o r bovine albumin. Case History T h e patient, aged 3 8 , w a s first seen o n March 1 2 , 1948, when s h e w a s admitted t o hospital a t t h e 33rd week o f gesta- tion i n h e r third pregnancy, o n account o f intrauterine foetal death. Her previous obstetrical history, which wa s somewhat chequered, wa s a s follows. 1 . On March 1 , 1929, sh e gave birth i n h e r o w n home t o a living female mature infant weighing 9 + l b. (4.3 kg.). Post- partum haemorrhage occurred and s h e w a s removed t o a non- obstetrical general hospital, where t w o blood transfusions were given o n th e d a y o f admission, each transfusion apparently of o n e pint (570 ml.) and each from a separate donor. Septicaemia supervened, b u t full recovery occurred after four weeks, when s h e wa s discharged. Unfortunately t h e transfusion records could n o t b e found a n d s o t h e donors could n o t b e traced. 2 . A stillborn male mature infant w a s born a t home o n January 2 1, 1932; weight unknown. Foetal movements were n o t felt b y the patient for s i x weeks before delivery. N o investigations were made. S h e divorced h e r husband i n 1936, b u t remarried i n June, 1947. T h e first husband, unfortunately, cannot be traced, a n d s o n o investigations o n h i s blood a r e possible. 3. On March 1 6 , 1948, a stillborn macerated male foetus wa s delivered; gestation 3 4 weeks. S he h a d booked f o r home

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Page 1: Kell-cellano Blood Group System

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N o v . 2 5 , 1 9 5 0 THERMAL COAGULABILITY OF SERUM PROTEINS l i o H n ^ 1 2 0 3

C l i f t o n ( 1 9 4 9 ) c o m p a r e d t h e r e s u l t s h e o b t a i n e d u s i n g

t h r e e " c a n c e r t e s t s " - n a m e l y , a n a n t i p r o t e o l y t i c r e a c t i o n

a n d t h e r m a l c o a g u l a t i o n t e s t s . U s i n g t h e i od o a c et a t e t e s t ,h e f o u n d n o s i g n i f i c a n t d i f f e r e n c e i n r e s u l t s w h e t h e r t h eo r i g i n a l t e c h n i q u e o f H u g g i n s e t a l . o r t h e i r l a t e r m o d i f i c a -

t i o n w a s a p p l i e d . T h e s e r e s u l t s a r e s h o w n i n s u m m a r i z e d

f o r m i n T a b l e I . I n h i s e n t i r e s e r i e s ( 2 3 5 c a s e s ) t h e o v e r a l la c c u r a c y i n c a n c e r d i a g n o s i s w a s o n l y 5 5 . 5 % .

B o d a n s k y a n d M c l n n e s ( 1 9 5 0 ) f o u n d t h e o r i g i n a l t e c h .

n i q u e r e c o m m e n d e d b y H u g g i n s e t a l . u n r e l i a b l e a n da d o p t e d t h e i r own m o d i f i c a t i o n o f t h e s e c o n d m e t h o dd e s c r i b e d . T h e i r r e s u l t s a r e s u m m a r i z e d i n T a b l e I .

H o m b u r g e r e t a l . ( 1 9 5 0 ) p u b l i s h e d a n a c c o u n t o f t h e i ri n v e s t i g a t i o n s a n d i n c l u d e d a d e t a i l e d l i s t o f c a s e s . T h e yu s e d b o t h t e c h n i q u e s d e s c r i b e d b y H u g g i n s e t a l . , a n d , a sw e h a v e d o n e , made a n a t t e m p t t o a s s e s s t h e r e l i a b i l i t ya n d r e p r o d u c i b i l i t y o f t h e t e s t . T h e y c o n d e m n t h e o r i g i n a lm e t h o d o f H u g g i n s e t a l . , m a i n t a i n i n g t h a t r e p r o d u c t i o n o f

t h e t e s t b y d i f f e r e n t i n v e s t i g a t o r s i s i m p o s s i b l e . T h e y c o n -

s i d e r t h e m o d i f i e d m e t h o d e a s i e r t o r e p r o d u c e a n d l e s s c o m -

p l i c a t e d , b u t f i n d t h e r e s u l t s s o o b t a i n e d a t c o n s i d e r a b l e

v a r i a n c e w i t h t h o s e f r o m t h e f o r m e r m e t h o d ( T a b l e I ) .

F i n a l l y , K i e f e r e t a l . ( 1 9 5 0 ) c a r r i e d o u t t h e m o d i f i e d

t e c h n i q u e o f H u g g i n s e t a l . o n 7 0 0 a p p a r e n t l y h e a l t h y m e na n d w o m e n . A l l e x c e p t s i x g a v e v a l u e s h i g h e r t h a n 9 . 3 .

T h e s e l a t t e r w e r e f o u n d t o g i v e f i g u r e s g r e a t e r t h a n 9 o n

r e p e t i t i o n . O f 2 5 c a n c e r c a s e s r u n a s c o n t r o l s , 76% g a v e

a p o s i t i v e t e s t . A c c o r d i n g t o t h e s e w o r k e r s " t h e t h e r m a l

c o a g u l a t i o n e n d - p o i n t i s s t r i k i n g a n d r e p r o d u c i b l e , " a n d " i nn o i n s t a n c e d i d m u l t i p l e d e t e r m i n a t i o n s o f t h e e n d - p o i n t

u p o n t h e s a m e s p e c i m e n v a r y m o r e t h a n o n e t u b e . "

T h e r e s u l t s o f t h e s i x g r o u p s o f i n v e s t i g a t o r s c l e a r l y s h o wn o c o n s i s t e n t c o r r e l a t i o n , s o t h a t t h e c o n c l u s i o n i s i n e v i t -a b l e t h a t t h e t e s t a s s u c h i s v a l u e l e s s . T h e f i g u r e s o b t a i n e d

b y C l i f f t o n ( 1 9 4 9 ) , H o m b u r g e r e t a l . ( 1 9 5 0 ) , a n d o u r s e l v e s ,a l l u s i n g t h e o r i g i n a l t e c h n i q u e , a r e d i r e c t l y c o m p a r a b l e ,

a n d c o n t r a s t s h a r p l yw i t h t h e

r e s u l t sq u o t e d b y H u g g i n s

e t a l . ( T a b l e I ) I

We h a d h o p e d t h a t t h e t e s t m i g h t h a v e some a p p l i c a t i o ni n t h e d i a g n o s i s o f m a l i g n a n t d i s e a s e i n t h e c h e s t o r

a b d o m e n . I n o u r e x p e r i e n c e , h o w e v e r , s t r o n g l y p o s i t i v et e s t s w e r e n e a r l y a l w a y s o b t a i n e d i n a c u t e a n d c h r o n i c

i n f l a m m a t o r y l e s i o n s o f t h e c h e s t a n d i n h a e m o r r h a g i cs t a t e s i n t h e a l i m e n t a r y t r a c t n o t a s s o c i a t e d w i t h m a l i g -n a n c y ( T a b l e I I ) .

T h e c o n c l u s i o n , t h e r e f o r e , i s t h a t t h e c h a n g e i n s e r u m

p r o t e i n s m a n i f e s t a s a l t e r e d t h e r m a l c o a g u l a b i l i t y i s n o t

i n v a r i a b l y p r e s e n t w i t h m a l i g n a n t d i s e a s e , e v e n i n c l i n i c a l l ya d v a n c e d l e s i o n s , a n d a l s o o c c u r s i n a h i g h p r o p o r t i o n o f

c a s e s w i t h n o n - m a l i g n a n t p a t h o l o g y a n d e v e n i n a p p a r e n t l y

h e a l t h y i n d i v i d u a l s . Th e c a u s e o f s u c h a c h a n g e i s n o tn e c e s s a r i l y r e l a t e d t o a n a l t e r a t i o n i n t h e t o t a l s e r u m p r o -

t e i n s . T h e n a t u r e o f t h e c h a n g e i s a s y e t o b s c u r e .

Summary

T h e t h e r m a l c o a g u l a b i l i t y o f s e r u m p r o t e i n s i n t h e p r e s e n c e

o f i o d o a c e t i c a c i d h a s b e e n e x a m i n e d i n 6 5 n o r m a l i n d i -v i d u a l s , 8 9 c a s e s o f m a l i g n a n t d i s e a s e , a n d 6 3 p a t i e n t s w i t h

o t h e r d i s e a s e s .

An " i o d o a c e t a t e i n d e x " h a s b e e n c a l c u l a t e d f o r e a c h s e r u m ;

t h i s h a s b e e n u s e d t o a s se s s c h a n g e s i n t h e c o a g u l a b i l i t y o f

s e r u m p r o t e i n s i n r e l a t i o n t o d i s e a s e . T h e d i s t r i b u t i o n p a t t e r n

o f t h e f i g u r e s s o o b t a i n e d l e a d s t o t h e c o n c l u s i o n t h a t t h e

d e t e r m i n a t i o n o f s u c h an i n d e x i s u s e l e s s i n t h e d i a g n o s i s o f

m a l i g n a n t d i s e a s e . No t o n l y m a y serum f r o m a p p a r e n t l yh e a l t h y i n d i v i d u a l s f u r n i s h i o d o a c e t a t e f i g u r e s f a l l i n g i n t o t h e

i n d e x r a n g e s u g g e s t e d f o r c a n c e r c a s e s , a n d v i c e v e r s a , b u t

m o s t c a s e s o f n o n - m a l i g n a n t d i s e a s e g a v e v a h i e s i n t h e " c a n c e r

r a n g e . "

Th e t e s t a l s o r e v e a l s no c o n s i s t e n t c o r r e l a t i o n b e t w e e n

" i o d o a c e t a t e i n d e x " a n d t h e s e v e r i t y o f t h e m a l i g n a n t c o n d i -

t i o n ; e v e n a d v a n c e d c a s e s o f c a n c e r m a y g i v e f i g u r e s i n t h e

" n o r m a l r a n g e . "REFERENCES

B o d a n s k y , O . , a n d M c I n ne s , G . F . ( 1 9 5 0 ) . C a n c e r , 3 , 1 .C l i f f t o n , E . E . ( 1 9 4 9 ) . J . n a t . C a n c e r I n s t . , 1 0 , 7 1 9 .H o m b u r g e r , F . , P f e i f f e r , P . H . , P a g e , O . , R i z z o n e , G . P . , a n d

B e n o t t i , J . ( 1 9 5 0 ) . C a n c e r , 3 , 1 5 .H u g g i n s , C . , M i l l e r , G . M . , a n d J e n s e n , E . V . ( 1 9 4 9 ) . C a n c e r

R e s . , 9 , 1 7 7 .K i e f e r , L . , S u l l i v a n , B . H . , a n d L i t t l e f i e l d , W. ( 1 9 5 0 ) . P r o c . S o c .

e x p . B i o l . , N . Y . , 7 3 , 2 9 .

KELL-CELLANO BLOOD GROUP SYSTEM

I N PREGNANCY AND TRANSFUSIONBY

J . B . COCHRANE, M . B . , M . R . C . O . G .

( F r o m N o t t i n g h a m C i t y H o s p i t a l )

R . H . MALONE, M . D . , D . P . H .

AND

L . DUNSFORD

( F r o m n t h e S h e f f i e l d B l o o d T r a n s f u s i o n C e n t r e )

C o o m b s , M o u r a n t , a n d R a c e ( 1 9 4 6 ) d e s c r i b e d a new

a n t i g e n - a n t i b o d y s y s t e m ( K e l l ) u n r e l a t e d t o t h e Rh s y s t e m

b u t n e v e r t h e l e s s c a p a b l e o f p r o d u c i n g h a e m o l y t i c d i s e a s eo f t h e n e w b o r n . More r e c e n t l y , L e v i n e e t a l . ( 1 9 4 9 ) f o u n d

a n o t h e r a n t i b o d y ( C e l l a n o ) w h i c h a l s o c a u s e d h a e m o l y t i c

d i s e a s e o f t h e n e w b o r n , a n d s h o w e d t h a t t h e K e l l a n d

C e l l a n o g e n e s a r e a l l e l e s . T h e y s u g g e s t e d t h a t t h e s y m b o l s

K a n d k , p r e v i o u s l y e m p l o y e d t o r e p r e s e n t K e l l - p o s i t i v ea n d K e l l - n e g a t i v e , b e u s e d t o i n d i c a t e t h e p r e s e n c e o f t h eK e l l a n d C e l l a n o g e n e s r e s p e c t i v e l y , a n d c a l c u l a t e d t h a t t h e

t h r e e g e n o t y p e s , K K, K k , a n d k k o c c u r w i t h f r e q u e n c i e so f 0 . 2 % , 8 . 6 % , a n d 9 1 . 2 % r e s p e c t i v e l y a m o n g w h i t e

A m e r i c a n s .

S i x e x a m p l e s o f a n t i - K e l l a r e n o t e d i n t h e i r p a p e r a n d a t

l e a s t a d o z e n o t h e r s a r e known a t t h e p r e s e n t t i m e ( R . R .

R a c e - p e r s o n a l c o m m u n i c a t i o n ) . T h e K e l l a n t i b o d y i n t h e

c a s e d e s c r i b e d h e r e was d i s c o v e r e d a t t h e S h e f f i e l d B l o o d

T r a n s f u s i o n C e n t r e i n 1 9 4 8 ( D u n s f o r d , 1 9 4 9 ) , a n d i s

e x c e p t i o n a l i n r e a c t i n g i n s a l i n e b u t n o t i n h uman s e r u m

o r b o v i n e a l b u m i n .

C a s e H i s t o r y

T h e p a t i e n t , a g e d 3 8 , w a s f i r s t s e e n o n M a r c h 1 2 , 1 9 4 8 ,w h e n s h e w a s a d m i t t e d t o h o s p i t a l a t t h e 3 3 r d w e e k o f g e s t a -

t i o n i n h e r t h i r d p r e g n a n c y , o n a c c o u n t o f i n t r a u t e r i n e f o e t a l

d e a t h . H e r p r e v i o u s o b s t e t r i c a l h i s t o r y , w h i c h w a s s o m e w h a t

c h e q u e r e d , was a s f o l l o w s .1 . On M a r c h 1 , 1 9 2 9 , s h e g a v e b i r t h i n h e r own h o m e t o a

l i v i n g f e m a l e m a t u r e i n f a n t w e i g h i n g 9 + l b . ( 4 . 3 k g . ) . P o s t -

p a r t u m h a e m o r r h a g e o c c u r r e d a n d s h e w a s r e m o v e d t o a n o n -

o b s t e t r i c a l g e n e r a l h o s p i t a l , w h e r e t w o b l o o d t r a n s f u s i o n s w e r e

g i v e n o n t h e d a y o f a d m i s s i o n , e a c h t r a n s f u s i o n a p p a r e n t l y o f

o n e p i n t ( 5 7 0 m l . ) a n d e ac h f r o m a s e p a r a t e d o n o r . S e p t i c a e m i as u p e r v e n e d , b u t f u l l r e c o v e r y o c c u r r e d a f t e r f o u r w ee ks , when

s h e w a s d i s c h a r g e d . U n f o r t u n a t e l y t h e t r a n s f u s i o n r e c o r d sc o u l d n o t b e f o u n d a n d s o t h e d o n o r s c o u l d n o t b e t r a c e d .

2 . A s t i l l b o r n m a l e m a t u r e i n f a n t w a s b o r n a t ho m e on

J a n u a r y 2 1 , 1 9 3 2 ; w e i g h t u n k n o w n . F o e t a l m o v e m e n t s w e r e

n o t f e l t b y t h e p a t i e n t f o r s i x w e e k s b e f o r e d e l i v e r y . No

i n v e s t i g a t i o n s w e r e m a d e . S h e d i v o r c e d h e r h u s b a n d i n 1 9 3 6 ,b u t r e m a r r i e d i n J u n e , 1 9 4 7 . T h e f i r s t h u s b a n d , u n f o r t u n a t e l y ,

c a n n o t b e t r a c e d , a n d s o n o i n v e s t i g a t i o n s o n h i s b l o o d a r ep o s s i b l e .

3 . On M a r c h 1 6 , 1 9 4 8 , a s t i l l b o r n m a c e r a t e d m a l e f o e t u s was

d e l i v e r e d ; g e s t a t i o n 3 4 w e e k s . S h e h a d b o o k e d f o r home

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1 2 0 4 N o v . 2 5 , 1 9 5 0 KELL-CELLANO bLOOD GROUP SYSTEM D I C j J O s U L

c o n f i n e m e n t w i t h h e r t h i r d p r e g h a n c y ( t h e f i r s t b y h e r s e c o n dh u s b a n d ) , a n d d e l i v e r y w a s d u e i n t h e l a s t w e e k o f A p r i l , 1 9 4 8 .A t t h e t h i r d m o n t h s h e h a d a t h r e a t e n e d a b o r t i o n , t r e a t e d b yh e r ow n d o ct or w it h r e s t i n b e d a t h o m e , a n d f r o m t h e no n w a r d s u n t i l M a r c h 1 , when s h e f a i l e d t o f e e l t h e f o e t a lm o v e m e n t s , t h e r e w e r e n o f u r t h e r c o m p l i c a t i o n s . H e r p a s th i s t o r y y i e l d e d n o i l l n e s s e s o f n o t e . E x a m i n a t i o n on M a r c h 1 2s h o w e d h e r t o b e a n o r i m a l h e a l t h y w o m a n , no a b n o r m a l i t y i nb l o o d p r e s s u re o r u r i n e b e i n g p r e s e n t . T h e W a s s e r m a n nr e a c t i o n a n d Kahn t e s t w e r e n e g a t i v e . T h e f u n d u s was s m a l l

f o r 3 3 w e e k s ' g e s t a t i o n , a n d t h e f o e t a l h e a r t s o u n d s w e r e a b s e n t .A s k i a g r a m o f t h e f o e t u s s h o w e d a w e l l - m a r k e d S p a l d i n g s i g n ,a n d s o i n d u c t i o n o f l a b o u r ' b y t h e i n s e r t i o n o f a s t o m a c h t u b ei n t o t h e l o w e r p o l e o f t h e u t e r u s w a s p e r f o r m e d on M a r c h 1 6 ,a n d 2 1 h o u r s l a t e r a m a l e s t i l l b o r n m a c e r a t e d f o e t u s w e i g h i n g3 l b . 8 o z . ( 1 . 6 k g . ) w a s d e l i v e r e d w i t h o u t e v e n t . H e r r e c o v e r yw a s s p o n t a n e o u s a n d s h e w a s d i s c h a r g e d o n M a r c h 2 6 . A tt h e p o s t - n a t a l e x a m i n a t i o n o n A p r i l 2 7 , when r e c o v e r y w a sc o m p l e t e , s h e w a s a d v i s e d t o r e p o r t i m m e d i a t e l y t o t h e h o s p i t a la n t e n a t a l c l i n i c i f a n y f u r t h e r p r e g n a n c y o c c u r r e d .

4 . On N o v e m b e r 1 3 , 1 9 4 9 , s h e g a v e b i r t h t o a l i v i n g m a l em a t u r e i n f a n t . S h e r e p o r t e d o n J u n e 1 , 1 9 4 9 , w h e n s h e s t a t e dt h a t h e r l a s t m e n s t r u a l p e r i o d h a d b e g u n o n F e b r u a r y 1 a n d s h et h Q u g h t s h e w a s p r e g n a n t . E x a m i n a t i o n s h o w e d h e r t o b e 1 6w e e k s a d v a n c e d i n p r e g n a n c y a n d h e r g e n e r a l c o n d i t i o n t o b e

w h o l l y n o r m a l . H e r a n t e n a t a l p r o g r e s s t o t e r m w a s s m o o t ha n d n o o b s t e t r i c c o m p l i c a t i o n s o c c u r r e d . On N o v e r i b e r 1 3 , a ss h e h a d n o t g o n e i n t o l a b o u r s p o n t a n e o u s l y a n d h a d e x c e e d e dt h e c a l c u l a t e d d a t e o f d e l i v e r y b y s o m e f i v e d a y s , a s u r g i c a li n d u c t i o n o f l a b o u r ( l o w r u p t u r e o f m e m b r a n e s ) w a s p e r f o r m e d ,a n d s i x h o u r s l a t e r s h e d e l i v e r e d h e r s e l f s p o n t a n e o u s l y o f al i v i n g m a l e m a t u r e i n f a n t , w e i g h i n g 6 - l b . ( 2 . 8 k g . ) . Th ep l a c e n t a a n d m e m b r a n e s s h o w e d n o a b n o r m a l i t y , e i t h e r m a c r o -s c o p i c a l l y o r m i c r o s c o p i c a l l y , a n d t h e i n f a n t w a s a t n o t i m ej a u n d i c e d o r a n a e m i c . B o t h m o t h e r a n d i n f a n t made n o r m a lp r o g r e s s a n d w e r e d i s c h a r g e d 1 0 d a y s a f t e r w a r d s . A t t h e p o s t -n a t a l v i s i t o n e m o n t h l a t e r t h e i n f a n t w a s m a k i n g e x c e l l e n tp r o g r e s s a n d t h e m o t h e r w a s o v e r j o y e d a t t h e s u c c e s s f u lo u t c o m e o f h e r p r e g n a n c y .

S e r o l o g i c a l I n v e s t i g a t i o n s

T h e p a t i e n t ' s b l o o d w a s f i r s t t e s t e d i n O c t o b e r , 1 9 4 7 , w h e ns h e w a s 1 4 w e e k s p r e g n a n t : n o a b n o r m a l a n t i b o d i e s w e r ef o u n d , b u t t h e l a b o r a t o r y r e c o r d e d " ? w e a k r e a c t i o n s w i t ht w o c e l l s ( C l a n d C 2 ) . " C , w a s known t o b e K e l l - p o s i t i v e ,b u t t h e K e l l t y p e o f C l w a s u n k n o w n , . a n d n o p a r t i c u l a rs i g n i f i c a n c e w a s a t t a c h e d a t t h e t i m e t o t h e s e d o u b t f u l r e a c t i o n s .( C 1 s u b s e q u e n t l y p r o v e d t o b e K e l l - p o s i t i v e a l s o . )

B l o o d c o l l e c t e d f r o m t h e m o t h e r a t t h e d e l i v e r y o f a s t i l l -b o r n c h i l d i n M a r c h , 1 9 4 8 , w a s f o u n d t o c o n t a i n a n t i - K e l l a c t i v ea t 3 7 0 C . i n s a l i n e a n d d e m o n s t r a b l e w i t h a n t i - h u m a n g l o b u l i n ,b u t i n a c t i v e i n human s e r u m o r b o v i n e a l b u m i n . T h i s i s o fi n t e r e s t , a s i t w a s t h e f i r s t s a l i n e a g g l u t i n a t i n g K e l l a n t i b o d yr e p o r t e d , a n d S a n g e r e t a l . ( 1 9 4 9 ) - h a d n o t e d t h a t a l l t h r e ee x a m p l e s o f t h e K e l l a n t i b o d y r e p o r t e d u p t i l l t h e n h a d b e e no f t h e i n c o m p l e t e t y p e , a n d t h a t t h i s f a c t w a s p r o b a b l y n o tw i t h o u t c l i n i c a l s i g n i f i c a n c e .

T h e p a t i e n t b e c a m e p r e g n a n t a g a i n i n F e b r u a r y , 1 9 4 9 , a n dw a s d e l i v e r e d o f a n o r m a l f u l l - t e r m c h i l d i n N o v e m b e r , 1 9 4 9 .H e r b l o o d w a s e x a m i n e d t h r e e t i m e s d u r i n g t h i s p r e g n a n c y -a t t h e 2 0 t h , 2 8 t h , a n d 3 5 t h w e e k s - a s w e l l a s a t d e l i v e r y a n do n t h e 1 4 t h d a y p o s t p a r t u m , a n d o n e a c h o c c a s i o n s a l i n ea g g l u t i n a t i n g a n t i - K e l l c o u l d b e d e m o n s t r a t e d . T h e t i t r e s i ns a l i n e o n t h e s e o c c a s i o n s w e r e 1 , 4 , 1 , 2 , a n d 2 r e s p e c t i v e l y ,a n d t h e c o r r e s p o n d i n g t i t r e s w i t h a n t i - h u m a n g l o b u l i n w e r e2 , 6 4 , 3 2 , 8 , a n d 3 2 . On n o o c c a s i o n d i d h e r s e r u m a g g l u t i n a t eK e l l - p o s i t i v e c e l l s s u s p e n d e d i n human s e r u m o r b o v i n e a l b u -m i n , a n d t h e Coombs t e s t a f t e r i n a c t i v a t i o n o f h e r s e r u m a t7 0 0 C . f o r 1 0 m i n u t e s w a s c o n s i s t e n t l y n e g a t i v e .

T h e p a t i e n t w a s G r o u p 0 R h - p o s i t i v e ( C D e / e D E ) , M, P , L e a -

n e g a t i v e , K e l l - n e g a t i v e , C e l l a n o - p o s i t i v e ( p r e s u m a b l y k k ) .H e r s e c o n d h u s b a n d w a s G r o u p B R h - p o s i t i v e ( C D e / C D e ) ,

MN, p , L e a - p o s i t i v e , . K e l l - p o s i t i v e , C e l l a n o - p o s i t i v e ( p r e s u m a b l yK k ) .

T h e b a b y w a s G r o u p 0 R h - p o s i t i v e ( C D e / C D e ) , MN, P ,? L e a - p o s i t i v e , K e l l - n e g a t i v e , C e l l a n o - p o s i t i v e ( p r e s u m a b l y k k ) .T h e d i r e c t Coombs t e s t w a s n e g a t i v e .

D i s c u s s i o n

I n t h e a b s e n c e o f r e c o r d s o f t h e b o t t l e s o f b l o o d t r a n s -f u s e d i n 1 9 2 9 a n d b e c a u s e o f o u r i n a b i l i t y t o t r a c e h e r f i r s t

h u s b a n d , i t i s n o t p o s s i b l e t o s a y w i t h c e r t a i n t y w h e t h e r

t h e p a t i e n t h a d b e e n i m m u n i z e d a g a i n s t t h e K e l l f a c t o r b yb l o o d t r a n s f u s i o n , p r e g n a n c y b y t h e f i r s t h u s b a n d , o r

p r e g n a n c y b y t h e s e c o n d h u s b a n d , wh o i s known t o b e

K e l l - p o s i t i v e . H o w e v e r , i n v i e w o f t h e f a c t t h a t t h e s e c o n dc h i l d o f h e r f i r s t h u s b a n d w a s s t i l l b o r n b u t m a t u r e , a n d

h e r t h i r d c h i l d , t h e f i r s t c h i l d o f h e r s e c o n d h u s b a n d , w a s

s t i l l b o r n , m a c e r a t e d , a n d o n l y 3 4 w e e k s i n g e s t a t i o n , t h ep r o b a b i l i t i e s a r e t h a t s h e w a s i m m u n i z e d b e f o r e h e r s e c o n d

m a r r i a g e a n d b y t h e b l o o d t r a n s f u s i o n i n 1 9 2 9 r a t h e r t h a n

b y h e r f i r s t o r s e c o n d c h i l d . I t w o u l d b e a r e m a r k a b l e

c o i n c i d e n c e i f h e r f i r s t h u s b a n d a n d h e r s e c o n d w e r e K e l l -p o s i t i v e , t h e o d d s b ei n g a b o u t 1 3 0 t o 1 a g a i n s t s u c h a n

e v e n t o c c u r r i n g .- T h i s i n v e s t i g a t i o n s u p p o r t s L e v i n e ' s v i e w t h a t t h e g e n e s

f o r t h e K e l l a n d C e l la no f a c t o r s a r e a l l e l o m o r p h i c , i n t h a tt h e h u s b a n d w a s K k , t h e w i f e k k , a n d t h e c h i l d k k . I t a l s od r a w s a t t e n t i o n t o t h e f a c t t h a t a n i n c r e a s i n g t i t r e o f a n

a n t i b o d y d u r i n g p r e g n a n c y d o e s n o t n e c e s s a r i l y i n d i c a t et h a t t h e f o e t u s c a r r i e s t h e c o r r e s p o n d i n g s p e c i f i c a n t i g e n .I n t h i s c a s e t h e f o e t u s w a s K e l l - n e g a t i v e , y e t t h e t i t r e o f

t h e m a t e r n a l a n t i - K e l l i n c r e a s e d d u r i n g p r e g n a n c y . T h i s

p h e n o m e n o n h a s b e e n o b s e rv ed o n many o c c a s i o n s i n t h ec a s e o f Rh a n t i b o d i e s , a n d i s b e l i e v e d t o b e o f t h e n a t u r e

o f a n a n a m n e s t i c r e a c t i o n , t h e f o e t u s p r o v i d i n g a n o n -

s p e c i f i c s t i m u l u s .T h i s K e l l a n t i b o d y i s p e c u l i a r i n r e a c t i n g i n s a l i n e a n d

w i t h a n t i - h u m a n g l o b u l i n b u t n o t i n h uman s e r u m o r

b o v i n e a l b u m i n . I n d e e d , a l b u m i n s e e m s t o s u p p r e s s i t s

a c t i v i t y i n s t e a d o f e n h a n c i n g i t .D u r i n g t h e s e i n v e s t i g a t i o n s , w i t h t h e u s e o f t h e p a t i e n t ' s

a n t i b o d y , t h e c e l l s o f t w o u n r e l a t e d p e r s o n s w e r e o b s e r v e d

t o g i v e much w e a k e r r e a c t i o n s t h a n t h e o t h e r K e l l - p o s i t i v e s ,a n d a n o t h e r c e l l w a s n o t a g g l u t i n a t e d i n s a l i n e s u s p e n s i o nb u t w a s s e n s i t i z e d , a s e v i d e n c e d b y a p o s i t i v e r e a c t i o n w i t ha n t i - h u m a n - g l o b u l i n s e r u m . T h i s s u g g e s t s t h a t v a r i a n t s o ft h e g e n e K e x i s t , some o f w h i c h ma y b e h a v e i n a manner

s i m i l a r t o Du c e l l s i n t h e R h e s u s c o m p l e x .

T h e p a t i e n t g e n e r o u s l y d on a t e d b l o o d c o n t a i n i n g t h i sv a l u a b l e a n t i b o d y , w h i c h h a s b e e n u s e d , t o g e t h e r w i t h a n t i -C e l l a n o s e r u m k i n d l y s u p p l i e d b y D r . P h i l i p L e v i n e , f o rd e t e r m i n i n g w h i c h K e l l - p o s i t i v e s a r e h o m o z y g o u s . S y s t e m -a t i c s e a r c h i s n ow b e i n g made f o r t h e K e l l a n t i b o d y i np r e g n a n c y a n d i n c a s e s i n w h i c h a t r a n s f u s i o n r e a c t i o n h a so c c u r r e d . T h e r e s u l t s o f t h e s e i n v e s t i g a t i o n s w i l l b e

p u b l i s h e d i n a n o t h e r p a p e r , b u t t h e y a l r e a d y d e m o n s t r a t e( i n c o n f i r m a t i o n o f t h e w o r k o f o t h e r i n v e s t i g a t o r s ) t w o

p o i n t s o f p r a c t i c a l s i g n i f i c a n c e : ( 1 ) t h e K e l l a n t i b o d y i s o f

c o n s i d e r a b l e c l i n i c a l i m p o r t a n c e a s a c a u s e o f - t r a n s f u s i o nr e a c t i o n s a n d o f h a e m o l y t i c d i s e a s e o f t h e n e w b o r n ; a n d

( 2 ) i t s p r e s e n c e c a n b e d e m on s t r at e d b y m e a n s o f t h ei n d i r e c t Coombs t e s t b u t w i l l n o t u s u a l l y b e d e t e c t e d b yr o u t i n e c r o s s - m a t c h i n g t e c h n i q u e s o r d i n a r i l y e m p l o y e d i nh o s p i t a l s .

R E F E R E N C E S

C o o m b s , R . R . A . , M o u r a n t , A . E . , a n d R a c e , R . R . ( 1 9 4 6 ) . L a n c e t ,

1 , 2 6 4 .D u n s f o r d , I . ( 1 9 4 9 ) . N a t u r e , 1 6 3 , 9 6 2 .L e v i n e , P . , W i g o d , M . , B a c k e r , A . M . , a n d P o n d e r , R . ( 1 9 4 9 ) .

B l o o d , 4 , 8 6 9 .S a n g e r , R . , B e r t i n s h a w , D . , L a w l e r , S . D . , a n d R ac e , R . R . ( 1 9 4 9 ) .

R e v . H e m , a t . , 4 , 3 2 .