Mixtures, mosaics and modifications

Mixtures, mosaics and modifications

Revue Fran~aise de Transfusion et Immuno-h6matoiogie Tome XIX - - N ° 1 - - 1976 247 Mixtures, mosaics and modifications by G.W.G. BIRD Regional Blo...

276KB Sizes 0 Downloads 37 Views

Revue Fran~aise de Transfusion et Immuno-h6matoiogie Tome XIX - - N ° 1 - - 1976

247

Mixtures, mosaics and modifications by G.W.G. BIRD Regional Blood T r a n s f u s i o n Service, BIRMINGHAM (England).

The finding of a mixed-field erythrocyte agglutination p a t t e r n is often the b e g i n n i n g of fruitful investigations which have c o n t r i b u t e d to general biological knowledge [15]. However, one m u s t first identify a significant mixed-field. There are two situations in which a mixedfield p a t t e r n is of no significance at all in this c o n t e x t : first, when a weak a n t i b o d y produces a few small a g g l u t i n a t e s ; a n d second, the finding of some inagglutinable cells, representing the tail end of a n o r m a l d i s t r i b u t i o n curve of antigen strength, even when strong antibody is present. The latter is difficult to distinguish f r o m a true mixture of two different cell populations when the m i n o r cell p o p u l a t i o n represents less t h a n 1% of the mixture. True mixtures may be classified as u n d e r : a) Artificial m i x t u r e s ; b) Those due to low n u m b e r s of blood group antigen sites; c) Chimaeras ; d) Those seen in m a l i g n a n t diseases of lymphoreticular tissue, in ,, somatic ,, m u t a t i o n , or in m o n o s o m y without a p p a r e n t disease; e) Polyagglutination. 1. - - ARTIFICIALMIXTURES Artificial investigation origin, of the t r a n s f e r of a

mixtures m u s t always be excluded before any serious of a mixed-field is u n d e r t a k e n . They m a y be of accidental consequence of transfusion, feto-maternal (or materno-fetal) therapeutic m a r r o w graft.

248

BIRD G.W.G.

2. - - Low BLOODGROUP ANTIGEN SITE DENSITY Weak f o r m s of A o r B m a y p r e s e n t not only as a p p a r e n t violations of Lan d s t ei n er' s law b u t as mixed-fields, the classical e x a m p l e of the latter being A 3 [10]. Weakening of A, B o r o t h e r antigens in old age or in v ar i o u s diseases, e.g. leukaemia, m a y also be responsible. Mixed-field reactions are also given by L u t h e r a n antigens and by Sd a. Sd a is discussed f u r t h e r in the section on polyagglutination. 3.

--

CHIMAERAS

C h i m aeras m a y be of artificial origin, f o r example, as the result of a t h e r a p e u t i c bone m a r r o w g r a f t or an intra-uterine b l o o d transfusion. TURNER et al. [17] have r e p o r t e d 5 children who h ad h ad intra-uterine transfusions, in w h o m d o n o r lymphocytes p e r si st ed post-natally f o r over one year. There are two types of n a t u r a l c h i m a e r a s : twin c h i m a e r a s and d i s p e r m i c c h i m a e r a s [14]. Although h u m a n c h i m a e r a s are n o t quite as r a r e as we once believed, they are still r a r e enough to be reported, p a r t i c u l a r l y as each new one illustrates scientific advances c o n s e q u e n t on n e w approaches and new techniques [19], such as c h r o m o s o m e studies and blood group gene t r a n s f e r a s e estimations. A c h i m a e r a w h o is k n o w n to be a t w i n is obviously classified as a t w i n chimaera. However, a twin in s o m e t i m e s a b o r t e d or a s s i m il a t e d so that it w o u l d then be difficult, at least in some cases, to distinguish b e t w e e n a twin c h i m a e r a and a d i s p e r m i c chimaera. D i s p e r m ic c h i m a e r a s may, of course, show evidence of t wo sets of p a t e r n a l genes a n d / or m a y show o t h e r evidence of mosaicism, e.g. skin p a t c h e s of different colours or eyes of different colours. It m u s t be mentioned, however, that differences in eye colour are no t necessarily indicative of dispermy. In the r e m a r k a b l e study by EDWARDS et al. [9] of monozygotic twins of different sex, the m a l e twin an X O / X Y mosaic h a d one blue and one green-brown eye. We have recently r e p o r t e d [1] a f e m a l e c h i m a e r a w i t h two r e d cell populations (93 % O and 7 % At) and an overwhelrning p r e p o n d e r a n c e of lymphocytes of the n o r m a l male karyotype, 46, XY. Our p at i en t was said not to be a t w i n and we w e r e u n a b l e to find evidence of dispermy. A family study showed that genes on c h r o m o s o m e s which d e t e r m i n e d h er m i n o r ery t h ro cyt e p o p u l a t i o n w e r e t r a n s m i t t e d to h er offspring. A sim i l ar example in a f e m a l e twin c h i m a e r a was r e p o r t e d at ab o u t the s a m e t i m e [8]. A f u r t h e r study of the B i r m i n g h a m c h i m a e r a showed t h a t h er A-gene specified t r a n s f e r a s e is at a n o r m a l level f o r an A t p e r s o n and that all h e r e r y t h r o c y t e s are coated w i t h A and A t Le b substance. We cannot say w h e t h e r these observations show t h a t she is really a twin because we do not k n o w of any c o m p a r a t i v e studies in d i s p e r m i c chimaeras.

MIXTURES, MOSAICS AND MODIFICATIONS

249

4. - - MALIGNANTDISEASE OF LYMPHORETICULARTISSUE, SOMATICMUTATION, AND MONOSOMYWITHOUTAPPARENTDISEASE Under this heading, I tentatively include the mosaics associated with myeloproliferative disease, e.g. polycythaemia vera, erythroleukaemia, which are discussed in the next section; and those without a p p a r e n t cause such as mosaic for Rhesus only [14, 11], a n d the strange case of JENKINS a n d MARSH [12] in which the two red cell populations differed in b o t h Rhesus a n d Duffy groups. Tn-polyagglutination m a y also come within this category [2]. 5. - - ERYTHROCYTE MOSAICISMIN DISEASE Erythrocyte mosaicism consequent on erythrocyte m e m b r a n e modifications in m a l i g n a n t disease of lymphoreticular tissue are of m u c h interest in b o t h haematology a n d i m m u n o h a e m a t o l o g y . They have been several interesting reports on erythrocyte mosaicism in myeloproliferative disease, such as the case reported by CALLENDERet al. [7], othe.r examples of Rh mosaicism [11], a n d the p a t i e n t of KAHN et al. [13] who had erythroleukaemia with n o r m a l A/weak A mosaicism and other interesting manifestations. We have investigated [6] a male p a t i e n t with acute erythroleukaemia who presented with a mixed-field agglutination p a t t e r n which, at first, appeared to be a m i x t u r e of group O (60 %) and group B (40 %) cells. However, investigation of the separated cell populations showed that he had in fact a m i x t u r e of n o r m a l B and very weak B cells. The latter were not agglutinated by anti-B b u t took up anti-B which could be recovered by elution. Transferase levels were very kindly determined by Professor Winifred WATKINS. The B-transferase level was at the lower limit of n o r m a l a n d the H-gene transferase level was normal. No other blood group systems were involved. I a n d i antigen strengths were normal. His chromosomes were of the n o r m a l male karyotype, 46, XY. Haemoglobin A 2 levels were normal, b u t the haemoglobin F level was raised (11.9 % of total haemoglobin). The general weakening of various blood group antigens in leukaemia [14] or Hodgkin's disease [16] are other examples of the effect of disease on blood groups. Microbial polyagglutination of the in vivo type, which is discussed below, is yet a n o t h e r category of mixed-field agglutination patterns a t t r i b u t a b l e to disease. Hereditary sideroblastic a n a e m i a with two red cell populations, one Xg (a +) and the other Xg (a-), has been described [18]. 6.

--

ERYTHROCYTE

POLYAGGLUTINATION

A classification of polyagglutination is given in T a b l e I. T-polyagglutination is so well k n o w n that we need not discuss it further. However, Tk-polyagglutination [3] in which erythrocytes are agglutinated by p e a n u t

250

BIRD G.W.G.

extract b u t which is different to T, seems to be of microbial origin. We have recently shown [5] that infection with Bacteroides fragilis is a cause of this condition. The relationship b e t w e e n T a n d Tk has not yet been clearly established. TABLE I

Classification of erythrocyte polyagglutination.

ACQUIRED

Passenger antigens, products, drugs

e.g.

bacterial

T Tk Acquired B Tn Artificial, e.g.D.F.E., periodate INHERITED

Cad Hempas

The Cad/Sd a blood group covers a wide s p e c t r u m of antigen strengths. The red cells of persons in the u p p e r ranges of a n t i g e n strength are polyagglutinable. N-acetyl-Dgalactosamine is the chief s t r u c t u r a l determ i n a n t of the Cad receptor. Acquired B, T n a n d Hempas are briefly dealt with in other papers. Lectins are very useful in studies of polyagglutination, particularly those of Arachis hypogaea (peanut), Dolichos biflorus, Salvia sclarea and Salvia h o r m i n u m [2, 4, 7]. With the p e a n u t and Salvia agglutinins alone, we can get a rapid indication of whether polyagglutinable red cells are T (or Tk), Tn or Cad (See table II of the paper on T n polyagglutination).

RESUME La possibilit6 d ' u n mdlange artificiel, d'origine accidentelle, consdquence d'une t r a n s f u s i o n ou d ' u n t r a n s f e r t fceto-maternel, doit t o u j o u r s 6tre 61iminde avec certitude a v a n t d'dtudier u n e image de double population d'h6maties. E n dehors d ' u n m61ange artificiel, u n e image de double p o p u l a t i o n peut ~tre rattach6e h l'un des cadres suivants :

--[aible densitd antigdnique : u n e image de double p o p u l a t i o n peut ~'observer dans le cas de certaines variantes faibles de groupes sanguins

MIXTURES, MOSAICS AND MODIFICATIONS

251

(A3) mais aussi de faqon habituelle dans certains syst6mes (Lutheran et Sd a) ; - - c h i r n & r e s : elles p e u v e n t 6tre d'origine artificielle p a r greffe de moelle osseuse ou t r a n s f u s i o n intra-ut6rine. P a r m i les chimbres naturelles, on distingue celles observ6es chez les j u m e a u x et les chim~res dispermiques ; - - mosa~que isoI~e : r e n t r e n t dans ce cadre les mosaiques isol6es au syst~me Rh sans q u ' a u c u n e cause ait pu y 6tre r a t t a c h d e ; - - m o s d i q u e Iide h u n e pathologie: l'6volution de certains maladies h6matologiques (leucdmies, maladie de Hodgkin) peut s'accompagner d'une image de double population des hdmaties. Les polyagglutinabilit6s d'origine m i c r o b i e n n e peuvent aussi r e n t r e r dans ce c a d r e ; - - p o l y a g g l u t i n a b i l i t ~ : les types T, Tk et B acquis sont acquis et transitoires. Le type Tn est 6galement acquis mais persistant. Cad et Hempas sont p a r contre des polyagglutinabilit6s h6r6ditaires.

Les lectines les plus utiles pour l'6tude de la polyagglutinabilit6 sont Arachis hypogaea, Dolichos biflorus, Salvia sclaera et Salvia horminum. I1 est possible, p a r ]eur utilisation, de d6finir r a p i d e m e n t le type T, T n o u Cad. Docteur G.W.G. BIRD, Regional Blood T r a n s f u s i o n Centre, Vincent Drive, Edgbaston, BIRMINGHAM B15 25G (England).

REFERENCES

[1] BATTEY D.A., BIRD G.W.G., MCDERMOT A., MORTIMER C.W., MUTCHINICK O.M., and WINGHAM 3. Another h u m a n chimaera. J. Med. Genet., 11, 283, 1974. -

-

[2] BIRD G.W.G., SHINTON N.K. and WINGHAM J. - - Persistent mixedfield polyagglutination. Brit. J. H a e m a t . , 21, 443, 1971. [3] BIRR GiW.G. and WINGHAMJ. - - Tk : A new form of red cell polyagglutination. Brit. J. H a e m a t . , 23, 759, 1972. [4] BIRD G.W.G. a n d WINGHAM J. - - H a e m a g g l u t i n i n s from Salvia. Vox. Sang., 26, 163, 1974. [5] BIRD G.W.G., WINGHAM J., INGLIS S. and MITCHELL A.A.B. - - Tkpolyagglutination in Bacteroides fragilis septicaemia. Lancet, 1, 286, 1975. [6] BIRD G.W.G., WINGHAMJ., CHESTER G.H., HILL D.M., KIDD P. a n d PAYNE R.W. - - Erythrocyte m e m b r a n e modification in m a l i g n a n t disease of lymphoreticular tissue II Erythrocyte mosaicism in acute erythroleukaemia. Brit. J. H a e m a t . , in press.

252

BIRD G.W.G.

[7] CALLENDER S.T., KAY H.E.M., LAWLER S.D., MILLARD R.E., GANGER R. a n d TIPPETT P. - - Two populations of Rh groups together with c h r o m o s o m a l l y a b n o r m a l cell lines in the bone marrow. Brit. Med. J., 1, 131, 1971. [8] CARR E.O. and MCDONALD L.A. - - Another example of h u m a n chimaerism. Transfusion (U.S&.), 14, 475, 1974. [9] EDWARDSJ.H., DENT T. a n d KAHN J. - - Monozygotic twins of different sex. J. Med. Genet., 3, 77, 1966. [10] FRIEDENREICH V. - - Eine bisher u n b e k a n l l t e Blutggruppeneigenshaft (A.~). Zft. f. I m m u n . Forsch., 89, 409, 1936. [11] HABIBI B., LOPEZ M. a n d SALMONC. - - Two new cases of Rh mosaicism Vox Sang., 27, 232, 1974. [12] JENKINS W.J. and MARSH W.J. - - Somatic m u t a t i o n affecting the Rhesus and Duffy systems. Transfusion (U.S.A.), 5, 6, 1965. [13] KAHN A., BOIVlN P., WROKLANS M. et HAKIM J. - - Erythroleuc6mie avec double p o p u l a t i o n 6 r y t h r o c y t a i r e : coexistence darts u n e marne p o p u l a t i o n d ' u n affaiblissement d ' u n antig6ne de groupe, d ' u n ddficit m a j e u r en ad6nylate-kinase et d'une a u g m e n t a t i o n de la fraction A2 de l'h6moglobine. Nouv. Rev. franf. Hdmat., 12, 609, 1972. [14] RACE R.R. a n d GANGERR . - Blood groups in Man, Blackwell, Oxford, 1968. [15] RACE R.R. a n d gANGER R. - - Blood group mosaics. Haematologia, 6, 63, 1972. [16] SCOTT G.L. a n d RASBRIDGEM.R. - - Loss of blood group antigenicity in a p a t i e n t with Hodgkin's disease. Vox Sang., 23, 458, 1972. [17] TURNER J.H., HUTCHINSON D.L. a n d PETRICCIANI J.C. - -

Chimerism following fetal transfusion. Report of leucocyte hybridisation and i n f a n t with acute lymphocytic leukaemia. Scand. J. Haemat., 10, 358, 1974. [18] WEATHERALLD.J., laEMBREY M.E., HALL E.G., GANGERR., TIPPETT P. and GAVIN J. - - Familial sideroblasfic a n a e m i a : p r o b l e m of Xg a n d X chromosome inactivation. Lancet, 2, 744, 1970. [19] WROBELD.M., MCDONALDI., RACE C. and WATKINSW.M. - - True genotype of chimeric twins revealed b y blood group gene products in plasma. Vox Sang., 27, 395, 1974.