TRANSFUSION Vol. 17

No. 6

November-December, 1977

Scientific Articles

Autoantibodies Mimicking Alloantibodies P. D. ISSITT,D. C . Z E L L N E RS,. D. ROLIH,A N D J. B. DUCKETT From the Paul 1. Hoxworth Blood Center of the University ofCincinnari. Cincinnati. Ohio and rhe Department of Medicine. Division of Hematofogy-Oncology. College of Medicine. Universitji of Cincinnati. Cincinnari. Ohio.

A patient with myelofibrosis, who has produced many red blood cell autoantibodies, is described. Although the patient is phenotypicaily R,R,(CDe/CDe), eluates made from his red blood cells have consistently contained what appeared to be anti-E, and more recently another antibody that appeared to be anti-c. In in virro experiments we have shown that the "anti-E" and "anti-c" can he totally adsorbed by E-negative and c-negative red blood cells, respectively. W e conclude thai the two antibodies have quite different specificities from those indicated by simple antibody identification studies, and that both are more closely related to the anti-Hr series of antibodies than to anti-E or anti-c.

W E I N E RET A L . ~ ' described a case of autoimmune hemolytic anemia (A.I.H.A.) in which the causative autoantibody had anti-e specificity. Since then many other blood group antibodies have been incriminated as causative of the disease. T h e Rh system has been implicated f~equently~.".'~."".:'" as have anti-Lw,.5.32 anti-Ull'. I8 and anti- W r '. I '. I Several groups of workers'-"~'"-''2.''".1' have pointed out that although anti-Rh antibodies a r e often involved, cases a r e seldom seen in which the specificity of the antibody is easily recognized. I n s t e a d , corn pl ex m i x t u r e s frequently involving anti-nl and/or anti-pdl and/or anti-dl, together with separable antiRh antibodies of "simple specificity," such as Received for publication October IS, 1976; accepted November 20, 1976.

anti-e and anti-c, a r e usually seen. Recently, in studying the autoantibodies of 150 individuals with positive direct antiglobulin tests (D.A.T.) and antibodies of the type seen in "warm-antibody" A.I.H.A., weI4 showed that in only four (2.7%) of the cases was a single "simple specificity" anti-Rh antibody involved. However, once adequate adsorption studies were completed it was shown that 56 (16%) of the 347 autoantibodies, formed by the 150 individuals, had "simple" anti-Rh specificity. If anti-nl and anti-pdl (both of which are anti-Rh-like) were included then 153 (44%) of the 347 autoantibodies were anti-Rh in nature. Not all individuals with positive D.A.T., and antibodies of this type, have A.I.H.A. C a r s t a i r s et al.4 and Worlledge e l al."" r e p o r t e d t h a t t r e a t m e n t with t h e antihypertensive drug alphamethyldopa (aldomet) frequently results in the development of autoantibodies that a r e serologically identical to those seen in A.I.H.A. Although the incidence of positive D.A.T. in these patients is fairly high, between 10 and 36 per cent,"' the incidence of hemolytic anemia is low, about 1 per cent."8 Some normal individuals a r e encountered in whom the D.A.T. is positive but inwhom t h e r e a r e no o t h e r hematologic abnor-

53 I Transfusion Nov:Dec. 1977

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ISSlTT ET A L

malities, nor any evidence for increased rates of in vivo red blood cell Of t h e 150 individuals studied,’.’ 87 h a d A.I.H.A.; 33 had positive D.A.T. due to ald o m e t therapy; and 30 were otherwise normal donors. W e report here a case in which a patient with myelofibrosis developed a strongly positive D.A.T. Over the course of the nearly two years during which we have studied this patient several different specificity autoantibodies have been identified, in eluates made from his red blood cells, and “free” in his serum. In spite of the production of these autoantibodies it does not seem that h e has suffered increased rates of in vivo red blood cell destruction. Multiple supportive red blood cell transfusions have been necessary because of red blood cell aplasia caused by myelofibrosis. While several of the autoantibodies eluted from his red blood cells have had expected specificities (based on his red blood cell phenotype) others have had specificities that suggested that they were allo rather than autoantibodies. T h e patient is R , R , (CDe/CDe) yet eluates from his red blood cells have consistently contained what appeared to be anti-E, and less frequently, an antibody that appeared to be anti-c. By adsorption studies with selected red blood cells we have shown that the “anti-E” and “antic” eluted from his red blood cells mimic antiE and anti-c, while having quite different specificities. Such “wrong” specificity antibodies, in eluates made from the red blood cells of patients with positive D.A.T., were first reported by Fudenberg et al. ‘I’

Case History G. M., a 76-year-old Caucasian male with a 15year history of hypertension and a myocardial infarction in 1972, noted increasing dyspnea with exertion and ankle swelling in June, 1974. He was noted to be anemic by his private physician and was treated with iron, folic acid, and vitamin Bi2 without response. He was admitted to a community hospital where he received eight units of blood. Evaluation for the etiology of his anemia was inconclusive and he was transferred to our hospital in September, 1974.

Transfusion Nov.-Dec. 1977

The initial evaluation of his blood revealed a red blood cell count of 4,l70,000/pl, hemoglobin I1.4gm/dl, hematocrit 35 per cent, reticulocyte count I per cent, white blood cell count 2,5OO/pl with 38 per cent polymorphonuclear cells, 56 per cent lymphocytes, 4 per cent monocytes, 1 per cent eosinophils and 1 per cent myelocytes and platelets 85,0OO/pl. The blood film showed aniso and poikilocytosis with tear drop forms, schistocytes, elliptocytes, and an occasional metamyelocyte. Bone marrow aspiration was attempted from the sternum but marrow was not obtained. A bone marrow biopsy was performed from the left posterior iliac spine. Hematoxylin and eosin stains revealed decreased cellularity, numerous megakaryocytes, and a moderate amount of fibrous tissue. The latter was confirmed by special stains for collagen. 59Fekinetic and ”Cr red blood cell sequestration and survival studies revealed bone marrow failure and shortened life span of the red blood cells but there was no evidence of red cell sequestration by the spleen. The leukocyte alkaline phosphatase score was, 133 (normal: 15 to 85). The chest x-ray showed mild cardiomegaly. A metastatic bone survey showed no osteosclerosis. Liver-spleen scan revealed a normal-sized liver and an enlarged spleen. The electrocardiogram showed a complete right bundle branch block and an old inferior myocardial infarction. The patient has required admission to the hospital approximately every six to seven weeks for transfusions of six to eight units of red blood cells. H e has received a 12-month course of oxymetholone, 100 mg orally daily, and a nine-month course of nandrolone decanoate, 200 mg subcutaneous weekly, without change in his transfusion requirement. In January, 1976, a liver biopsy revealed acute hepatitis with severe hemosiderosis and moderate extramedullary hematopoiesis. T h e hepatitisassociated antigen ( H BsAg) test was negative. In October, 1974, he was found to have a p s i tive D.A.T. At that time the serologic studies, reported in detail below, were begun. Since October, 1974, we have tested blood samples from G.M. on a regular basis. While the pattern of autoantibodies, in eluates made from his red blood cells and in his serum, has varied from time to time, there have been some consistent findings. In spite of the many autoantibodies that G.M. has produced it does not seem that he has suffered an increased rate of in vivo red blood cell destruction. Several findings point to this conclusion. First, G.M.’s transfusion requirements have not changed since his D.A.T. became positive. Second, his serum haptoglobin levels have consistently been normal. Third, there has been

Volume 17 Number6

AUTOANT 1 BOD1 ES

no disproportionate rise in the indirect fraction of his serum bilirubin. Methods The methods for D.A.T., antibody detection and identification, and preparation of enzymemodified red blood cells for antibody studies, were standard ones that have been described elsewhere.I3 Anti-nl, anti-pdl, and anti-dl were identified using the criteria set by Weiner and V O S ~ which .~ are also described e1~ewhere.I~ All antibody adsorptions involved mixing a volume of serum or eluate with an equal volume of washed, packed red blood cells of an appropriate phenotype. The mixtures were incubated at 37 C for 60 minutes before being centrifuged so that the adsorbed sera or eluates could be harvested. All eluates were made by the Rubin ether method.26 Each time that an eluate was prepared the saline, used to wash the red blood cells for the final time before preparation of the eluate, was also tested for antibody activity. In all instances these “last wash” saline solutions were nonreactive in antibody detection tests. We regard these controls as highly significant since we were apparently often recovering, by elution, antibodies with unexpected specificities. Results

Early in the course of this investigation, and at a time when no transfused red blood cells were detectable circulating in vivo. we showed G.M. to be group A , B ; D + , C + , E - , c - , e + , for an Rh phenotype of R I R I (C De/C De). At the time that G.M.’s blood was first studied by us in October, 1974, immediately after his D.A.T. became positive, his serum was found to contain anti-E, which was assumed to be an alloantibody. However, at the same time, an eluate made from his E-negative red blood cells contained apparently a single antibody, reacting only with E-positive red blood cell samples. Because of this contradictory finding (apparent antiE eluted from E-negative red blood cells) adsorption studies were undertaken. It was shown that a single adsorption with R2R2(cDE/cDE) red blood cells removed all antibody activity from the eluate. Single adsorptions with R I R , (CDe/CDe) and rr (ce/ce) red blood cells left some apparent anti-E unadsorbed. However, two additional adsorptions with R , R , o r r r red blood cells exhausted all antibody activity of the eluate. We then made eluates from the R , R , and rr red blood cells used to adsorb the G.M. eluate. In each instance we were able to recover an antibody that, based on its reactions in indirect antiglobulin tests

533

against a panel of fully-typed red blood cells, appeared to have anti-E specificity. Thus the anti-Elike antibody recovered, by elution, from G.M.’s E-negative red blood cells could be adsorbed onto, and recovered from, other E-negative ( R I R , and rr) samples. Because of these findings, G.M.’s serum, which also appeared to contain anti-E, was adsorbed with the same R,R,, R , R I , and rr red blood cells as had been used to adsorb his eluate. After two adsorptions with RZR2red blood cells all antibody activity had been removed. However, six adsorptions with R , R , or rr red blood cells failed to cause any appreciable reduction in the strength of the serum anti-E. Following these adsorption studies on G.M.’s s e r u m , anti-E could be recovered, by elution, from the R,R, but not the R , R , or rr red blood cells used in the adsorptions. These findings clearly indicated that the anti-E in G.M.’s serum, and the apparent anti-E in the eluate from his red blood cells, were not of the same specificity. Although possible interpretations of these findings are discussed fully below, it is necessary here to introduce a means of differentiating between the serum anti-E that bound only to E-positive red blood cells, and the eluted, apparent anti-E, that could be adsorbed onto, and eluted from, any E-negative red blood cells. For the remainder of this results section the serum antibody will be called “anti-E,” and the anti-E-like antibody eluted from G.M.’s E-negative red blood cells will be called “anti-E.” Samples collected from G.M. in January, 1975, yielded identical results to those described above. By March, 1975, the eluate from his red blood cells contained additional antibody activity. This eluate gave 4+ reactions with E-positive, and 2+ reactions with E-negative red blood cells with “normal” Rh phenotypes, but failed to react with D-- and Rh,,,, samples. Thus the eluate appeared to contain “anti-E” and anti-nl. Adsorption and elution studies showed that both antibodies could be adsorbed by, and eluted from, R,R,, R , R I , and rr red blood cells. The “anti-E” still fixed more readily to R,R, than R , R , or rr red blood cells but when eluates were made, from each of the adsorbing red blood cell samples, the “anti-E” specificity could still clearly be seen, being much stronger in reactivity than the anti-nl. Table 1 gives the results of all specificity studies performed on the autoantibodies eluted from G.M.’s red blood cells, and on the alloantibodies and ‘‘free’’ autoantibodies found in his serum, during the period from October, 1974, to August, 1976. As can be seen, G.M.has, at various times, produced anti-nl, anti-pdl, and anti-dl. These antibodies have behaved exactly as expectedI3.’j5 in adsorption and elution studies with “normal Rh

5 34

Transfurion

ISSITT ET A L Table 1.

Nov.-Oec. 1977

G.M.’s Antibodies

Date

Alloantibodies in Serum

”Free” Autoantibodies in Serum

Autoantibodies in Eluates from Red Blood Cells

10- 1 4 - 7 4 1-15-75 3-13-75 4-2 3- 7 5 5-25-75

Anti-E Anti-E Anti-E Anti-E Anti-E

None None Anti-nl None ”Anti-E”

7 - 17 - 7 5 9-11-75 10-31-75

Anti-E Anti-E Anti-E

“Anti-E” ”Anti-E” ”Anti-E”

1 2 - 10-75

Anti-E

12-22-75

Anti-E Anti-low incidence’ Anti-E

Anti-dl. “Anti-E,” “Anti-c” ”Anti-E”

“Anti-E” “Anti-E” Anti-nl. ”Anti-E” Anti-nl. “Anti-E” Anti-nl. Anti-pdl, ”Anti-E“ Anti-nl. “Anti-E” Anti-nl. “Anti-E” Anti-nl. Anti-dl. ”Anti- E” Anti-nl. Anti-dl. ”Anti-E.” “Anti-c” “Anti-E”

1-23-76 3-16-76 5-29-76

8- 2-76

Anti-E Anti-low incidence’ Anti-E

Anti-nl, “Anti-E.” ”Anti-c” Anti-nl, ”Anti-E.” “Anti-c“ “An ti- E”

Anti-E, Anti-K, Anti-Kpa

Anti-nl. ”Anti-E,“ “Anti-c”

~~

~~~~~~~~

Anti-nl, “Anti-E.” “Anti-c” Anti-nl, “Anti- E.” “Anti-c” Anti-nl. “Anti-E,” “Anti-c” Anti-nl, ”Anti-E.” ”Anti-c” ~

NOTES: Anti-E is the alloantibody reacting only with E-positive red blood cells; “Anti-E” is the anti-Hr-like antibody with a ”preference” for E-positive red blood cells (see discussion), ”Anti-c” is the anti-c-like antibody that could be totally adsorbed with R,R, ICDeICDe) red blood cells. Some tests to differentiate between anti-nl. anti-pdl and anti-dl were adsorptions. others involved the use of untreated and enzyme premodified red blood cells. *Unidentified antibody against a low incidence antigen (see text).

phenotype,” D- - and Rh,,,, red blood cells. At the same time, all eluates have contained the “anti-E” which has continued to behave as described above, in all adsorption and elution studies. Throughout the investigation, anti-E has been present in G.M.’s serum (all of his I16 transfusions were with R, R , blood) though adsorptionelution experiments have demonstrated that, on some occasions, smaller quantities of free “antiE” have also been present. As can be seen from Table I , in December, 1975, an additional antibody with apparent anti-c specificity, was found in the eluate from G.M.’s red blood cells. In adsorption studies this antibody could be totally removed from the eluate by single adsorptions with R,R, (cDE/cDE) or rr (ce/ce), or two adsorptions with R , R i (CDe/CDe), red blood cells. Since this anti-c-like antibody could be adsorbed from the eluate with c-negative ( R , R , ) red blood cells, we shall call the antibody “anti-c.” An antibody with apparent anti-c specificity was also found in G.M.’s serum. However, unlike the serum anti-E which could only be adsorbed onto, and eluted from, E-positive red blood cells, the

serum anti-c-like antibody could be adsorbed to exhaustion with c-negative ( R , R , ) red blood cells like the “anti-c” in G.M.’s eluate. Neither the eluted, nor t h e s e r u m , “anti-c” could be recovered, by elution, from the adsorbing R , R , red blood cells. However, we believe that this is simply a reflection of the weakness of the “anti-c” as compared with the “anti-E.” From all of these findings, and as shown by the results listed in the table, from December, 1975, onward, eluates from G.M.’s red blood cells have contained “antiE” and “anti-c” (together with anti-nl), while his serum has contained a potent allo-anti-E, a weaker “anti-E” and some “anti-c.” There is no evidence to suggest that G.M. has made an alloanti-c, and indeed no reason to expect that he would since he has been transfused exclusively with c-negative ( R , R , ) blood. In the course of the many serologic investigations that have been performed on the blood of G.M. some other observations have been made. First, the reactions of the various autoantibodies, described above, were not influenced in any way by the LW status of the test red blood cells. We

Volume 17 Numbcrh

A UTOANTl BOD1 ES

used LW:,,36and LW,,9,“6red blood cell samples in the investigations and t h e i r reactions were identical to LW-positive samples with the same Rh phenotypes. Second, adsorption studies at times when G.M. had anti-dl or anti-pdl present, yielded no evidence to suggest that anti-U, antiWrb or anti-Ena were present. Third, in the course of investigating G.M.’s serum we encountered very occasional, E-negative red blood cell samples that reacted very strongly. Although attempts to identify additional antibodies, directed against low incidence antigens, were not successful, w e assume that the presence of such antibodies accounts for these reactions. A large proportion of individuals who form multiple autoantibodies also form alloantibodies directed against very rare antigens.’:’ Fourth, G.M. has recently (August, 1976) produced anti-K and anti-Kp”. We have no evidence to suspect that these are other than normal alloantibodies produced as a result of his multiple transfusions. Discussion This case represents one in which the specificities of the auto anti bodies involved were different from those that appeared to be indicated by antibody identification studies. It is already known that some anti-Rh antibodies show marked “preferences” for red blood cells of certain phenotypes when indirect antiglobulin tests a r e performed, but that adsorption studies reveal that some weakly, or even nonreactive, red blood cell samples carry small amounts of the antigens against which the antibodies a r e directed. As examples, Rosenfield‘2 has observed that anti-hr’ reacts better with red blood cells from individuals who have ce cis genes than with those from individuals who have Ce cis genes. In spite of this, almost all C D e / C D e bloods a r e hr’-positive. This means, of course, that in initial studies anti-hr‘ might well mimic anti-c or anti-f, but that in adsorption studies C D e / C D e red blood cells (which a r e c-negative, f-negative) invariably adsorb anti-hr’ to exhaustion. A similar situation exists with anti-hr’ which “prefers” red blood cells from individuals with Ce cis genes to those from individuals with ce cis genes.2:’Such was the preference of anti-hr’ for C-positive red blood cells that the original

535

Bastiaan serum27 was believed to contain anti-C until it was found that this specificity could not be isolated by adsorption. I n working with the sera from a series of individuals with highly exotic Rh phenotypes (Shabalala, Davis, Santiago, Ellington, and Fentry) Rosenfield,2’ observed some reactions that were very similar to those of the “anti-E” in G.M.’s eluate. Although these observations” have never been published in full, they were mentioned briefly in a 1962 paper by Rosenfield et al.’s In several of the sera studied, t h e r e were antibodies t h a t showed very marked preferences for E o r e. These antibodies were shown not to be anti-E o r anti-e, by adsorption studies with red blood cells of appropriate phenotypes. It was shown that an antibody with a preference for E could be readily adsorbed with E+,e-, or E + , e + , red blood cells but that E-,e+, samples would eventually totally adsorb the antibody as well. In several instances the antibody-makers were Hr-negative so that their antibodies resembled the anti-Hr that is o f t e n m a d e a s an alloantibody by D- - / D - - o r Dc-/Dc- individuals. Since anti-nl, the antibody often encountered as an autoantibody in A.I.H.A., has (ostensibly a t least) a similar specificity to anti-Hr (reacts with all red blood cells with “normal” Rh phenotypes but not with those that a r e D-- or Rh,,,,) it seems, to us, that therein lies the explanation of why an apparent antiE could be eluted from G.M.’s E-negative red blood cells. Studies on alloantibodies called “anti-Hr” have shown that the term is almost certainly used to describe a group of antibodies with somewhat similar, yet not identical, specificities.” Since examples of anti-Hr a r e seen that have a preference for E, or for e, we believe that G.M. produced an auto-anti-Hr that gave positive reactions (in indirect antiglobulin tests) only with E-positive red blood cells, but which also bound to its antigen (as shown by adsorption and elution studies) on all E-negative samples with “normal” Rh phenotypes. The difference between the individuals studied by Rosen-

5 36

ISSITT ET AL.

field,z2 and G.M., is that the former made alloantibodies while G.M. made autoantibodies. The similarities in antibody specificities are not surprising. Many 14.30-32.34.35 on the causative autoantibodies of A.I.H.A., have shown close similarities between their specificities and those of alloantibodies of the Rh system. A parallel explanation to that used to explain the “antiE,” can be used to explain the “anti-c,” formed later by G.M., that could be adsorbed to exhaustion with c-negative red blood cells. G.M. formed a genuine allo-antiE (present in his serum only) that reacted only with the E antigen. There are some suspicions‘L.l’’that the reactions of some anti-Rh antibodies are influenced by the LW status of the red blood cells against which they are tested. There is no evidence, here, to believe that the reactions of G.M.’s anti-Hr-like autoantibodies (“anti-E” and “anti-c”) were in any way dependent on LW antigens, or on antigens that might be produced by interaction between the L W and CDE genes. We suspect that the situation described in this report may not be particularly uncommon. It was first reported in 1958” and we have seen other cases in which “anti-E” or “anti-C” or “anti-c” could be eluted from the red blood cells of patients with positive D.A.T. when the patients lacked the Rh antigen against which the autoantibody was apparently directed. Some of these cases are still under investigation and will be reported in more detail at a later date. Although the number of cases studied is still small, the early indications are that this phenomenon might be more common in “normal” individuals with positive D.A.T. than in patients with A.I.H.A., although both groups are represented in our series. T h e r e have been several o t h e r reportsi.6. l 3 . 1 5 . 2 X of “wrong” anti-Rh antibodies being eluted from red blood cells with positive D.A.T. This finding has, in the past, been attributed to the M a t u h asi- Oga t a p h e n ~ m e n o n . ” ~W~ e~ have, ~ ~ ” ourselves,

Transfusion Nov.-l)ec. 1977

classified this recovery of large quantities of “wrong” antibody, bound in vivo, as the “Super” Matuhasi-Ogata phenomenon and have contrasted it to the Matuhasi-Ogata “minimus” condition when only small amounts of “wrong” antibody are recovered in in vitro experiments.I3 Bove et al.,” have satisfactorily explained the “minimus” condition as representing nonspecific uptake of IgG by antibody-coated red blood cells. In r e t r o s p e c t we wonder i f t h e “ S u p e r ” Matuhasi-Ogata phenomenon may (on some occasions a t least) have represented the situation w e have described with G.M. In discussing this case with us, Rosenfieldz4suggested that G.M. might be producing just anti-E, but that his antibody-producing cells might be making a poorly defined population of antibody molecules that are capable of binding to E-negative, as well as Epositive, red blood cells. This is a similar idea to one proposed by Fudenberg et al.“ at a time when a n t i - H r had not been f u l l y characterized and before the “preference” of some anti-Hr antibodies for E-positive red blood cells had been demonstrated.2R We prefer to think of G.M.’s “anti-E” as anti-Hr with a preference for E, rather than as antiE. It seems, to us, that use of the term “antiE” to d e s c r i b e this antibody would considerably confuse the original definition of anti-E specificity.2’,3iA situation might then arise analogous to current confusion about anti-C. It is now not certain whether the antiC made by D-. c - , people who have also produced “blocking” anti-D, and the anti-C m a d e by D + , C - , people have identical specificities and, if not, which one should be called anti-C.z5 Finally, since we have encountered this phenomenon several times, we would caution against assigning “simple” anti- Rh specificity to any antibody, eluted from the red blood cells of an individual with a positive D.A.T., until it has been shown that the antibody cannot be adsorbed onto, and eluted from, red blood cells lacking the antigen against which it is apparently directed.

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Number6

24.

MacKenzie, M. R.: Positive direct Coombs tests with anti-IgA antiserum. Vox Sang. 19:451, 1970. Marsh, W. L., M. E. Reid, and E. P. Scott: Autoantibodies of U blood group specificity in autoimmune haemolytic anaemia. Br. J. Haematol. 22:625, 1972. Matuhasi, T., H. Kumazawa, and M. Usui: Question of the presence of so-called cross-reacting Blood Transf. 6:295, 1960. antibody. J. Jap. SOC. Nugent, M. E., K. 1. Colledge, and W. L. Marsh: Auto-immune hemolytic anemia caused by antiU. Vox Sang. 20519, 1971. Ogata, T., and T. Matuhasi: Problems of specific and cross reactivity of blood group antibodies. Biblio. Haematol. 13:208, 1962. -, and T. Matuhasi: Further observations on the problems of specific and cross reactivity of blood g r o u p antibodies. Biblio. H a e m a t o l . 19528, 1964. Race, R. R., G. L. Taylor, K. E. Boorman, and B. E. Dodd: Recognition of Rh genotypes in man. Nature 152563, 1943. Rosenfield, R. E.: T h e complexity of the Rh blood group system as revealed by unusual instances of isoimmunization. Unpublished manuscript, 196 I . -: Unpublished observations 1974, cited by Issitt, P. D., and C. H. lssitt in Applied Blood Group Serology, 2nd ed. Spectra Biologicals, Oxnard, 1975. -: Personal communication, 1976.

25.

-,

Acknowledgment

15.

We would like to thank Dr. Richard E. Rosenfield for giving us a copy of his unpublished manuscript,22for allowing us to cite data from it, and for making helpful suggestions during the preparation of this report.

16.

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Allen, F. H., Jr., P. D. Issitt, T. J. Degnan, V. A. Jackson, J. K. Reihart, R. J. Knowlin, and M. E. Adebahr: Further observations on the MatuhasiOgata phenomenon. Vox Sang. 16:47, 1969. Beck, M. L., D. McGuire, and C. Richardson: A fatty-acid dependent antibody with Rh specificity. Prog. 25th Ann. Mtg. AABB and 13th Cong. ISBT, Washington, D.C., 1972, pp 6, (Abstract), Supplemented with data presented but not included in the abstract nor published elsewhere. Bove, J . R., A. M. Holburn, and P. L. Mollison: Non-specific binding of IgG to antibody coated red cells. The “Matuhasi-Ogata” phenomenon. Immunology 25:793, 1973. Carstairs, K. C., A. Breckenridge, C. T. Dollery, and S. M. Worlledge: Incidence of a positive direct Coombs’ test in patients on alphamethyldopa. Lancet 2:133, 1966. Celano, M. J., and P. Levine: Anti-LW specificity in autoimmune acquired hemolytic anemia. Transfusion 7:265, 1967. Clancey, M., S. Bonds, and J. van Eys: A new example of anti-Lan and two families with Lannegative members. Transfusion 12:106, 1972. Dacie, J. V.: Acquired haemolytic anaemias. Br. Med. Bull. 15:67, 1959. -, and M. Cutbush: Specificity of auto-antibodies in acquired haemolytic anaemia. J. Clin. Pathol.7:18, 1954. deVeber, L. L., G. W. Clark, M. Hunking, and M. Stroup: Maternal anti-LW. Transfusion I I :33, I97 I . Fudenberg, H. H., R. E. Rosenfield, and L. R. Wasserman: Unusual specificity of auto-antibody in auto-immune hemolytic disease. J . Mt. Sinai Hosp. 25:324, 1958. Goldfinger, D., H. Zwicker, G. A. Belkin, and P. D. Issitt: An autoantibody with anti-Wrb specificity in a patient with warm autoimmune hemolytic anemia. Transfusion 15:35 I , 1975. Holllnder, L.: Study of the erythrocyte survival time in a case of acquired haemolytic anaemia. Vox Sang. (O.S.)4:164, 1954. Issitt, P. D., and C. H. Issitt: Applied Blood Group Serology, 2nd ed. Spectra Biologicals, Oxnard, 1975. -, B. G. Pavone, D. Goldfinger, H. Zwicker, C. H. Issitt, J . A. Tessel, S. W. Kroovand, and C. A. Bell: Anti-Wrb, and other autoantibodies responsible for positive direct antiglobulin tests in 150 individuals. Br. J. Haematol. 3 4 5 , 1976.

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Svardal, J. M., J. Yarbro, and E. J. Yunis: Ogata phenomenon explaining the unusual specificity in eluates from Coombs positive cells sensitized by autogenous anti-I. Vox Sang. 13:472, 1967. van Loghem, J. J., and M. van der Hart: Varieties of specific autoantibodies in haemolytic anemia. Vox Sang. (O.S.)4:2, 1954. Vos, G. H., L. Petz, and H. H. Fudenberg: Specificity of acquired haemolytic anaemia autoantibodies and their serological characteristics. Br. J. Haematol. 1957, 1970. -, L. D. Petz, and H. H. Fudenberg: Specificity and immunoglobulin characteristics of autoantibodies in acquired hemolytic anemia. J. Immunol. 106:1172, 1971. -, L. D. Petz, G. Garratty, and H. H. Fudenberg: Autoantibodies in acquired hemolytic anemia with special reference to the LW system. Blood 42:445, 1973.

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35. 36.

37.

38.

39.

ISSITT ET AL. Weiner, W.: “Coombs positive” “normal” people. Biblio. Haematol. 23:35, 1965. -, D. A. Battey, T. E. Cleghorn, F. G. W. Marson, and M. J. Meynell: Serological findings in a case of haemolytic anaemia; with some general observations on the pathogenesis of this syndrome. Br. Med. J. 2:125, 1953. -, and G. H. Vos: Serology of acquired hemolytic anemias. Blood 22:606, 1963. White, J. C., S. Rolih, S. L. Wilkinson, B. J . Hatcher, and P. D. Issitt: A new example of anti-LW and further studies on heterogeneity of the system. Tranfusion 15:368, 1975. Wiener, A. S., and E. 8. Sonn: Additional variants of the Rh type demonstrable with a special human anti-Rh serum. J. Immunol. 47:461, 1943. Worlledge, S . M . : Autoantibody formation associated with methylodopa (Aldomet) therapy. Br. J. Haematol. 165, 1969. -: Immune drug-induced hemolytic anemias. Sem. Hematol. 10:327, 1973.

Transfusion No”.-Dec. 1977

K. C. Carstairs. and J. V. Dacie: Autoimmune haemolytic anaemia associated with alphamethyldopa therapy. Lancet 2:135, 1966. and M. A. Blajchman: The autoimmune 41. -, haemolytic anaemias. Br. J . Haematol. (Supp1.)23:61, 1972. 40. -,

Peter D. Issitt, F.I.M.L.S., L.I. Biol., Director of Laboratories and Associate Professor of Research Surgery. Susan D. Rolih, M.S., M.T. (ASCP)SBB, Laboratory Supervisor. Judy B. Duckett, M.T. (ASCP), Technologist, Reference Laboratory, The Paul I. Hoxworth Blood Center o f the University of Cincinnati, 3231 Burnet Avenue, Cincinnati, Ohio 45267. David C. Zellner, M.D., Professor of Medicine, Division of Hematology-Oncology, College of Medicine, University of Cincinnati, 234 Goodman Street, Cincinnati, Ohio 45267.

Post-Doctoral Training Program in Blood Banking and lmmunohematology T h e New York Blood Center, Inc., offers a post-doctoral training program for qualified physicians interested in a career in blood banking. T h e facilities of T h e New York Blood Center’s Greater New York Blood Program, and four participating, university-atfiliated hospitals provide experience in regional blood program management, clinical blood transfusion therapy and blood bank technology. administration and problem solving. Instruction in immunohematology, serology and genetics, transplantation and tissue typing, blood fractionation. coagulation, cyrobiology and protein chemistry is provided utilizing the resources o f The New York Blood Center’s Lindsley F. Kimball Research Institute, Blood Derivatives Program and New York-New Jersey Regional Transplant Program. T h e Program is accredited by the Department of Education of the S t a t e of New York and the Veterans Administration. Fellowships a r e olTered for at least one year of training. Requirements:

I . An M.D. degree with a minimum of one year postdoctoral training in clinical medicine or pathology. 2. U.S. citizenship or permanent residency.

Applications for the program beginning July I , 1978 must be received before February I , 1978. Further information may be obtained from Dr. Benjamin Alexander. Associate Director for Educational Programs, T h e New York Blood Center, 310 East 67th Street, New York, NY 10021.

Autoantibodies mimicking alloantibodies.

TRANSFUSION Vol. 17 No. 6 November-December, 1977 Scientific Articles Autoantibodies Mimicking Alloantibodies P. D. ISSITT,D. C . Z E L L N E RS,...
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