Vox Sang. 33: 299-303 (1977)

Transient LW-Negative Red Blood Cells and Anti-LW in a Patient with Hodgkin’s Disease1

H. A . Perkins, M. Mcllroy, J . Swanson and M. Kadin

Irwin Memorial Blood Bank of the San Francisco Medical Society; Division of Hematology and Cancer Research Institute, University of California, San Francisco, Calif.; Philip Levine Laboratories, Ortho Diagnostics, Raritan, N.J., and University of Minnesota, Minneapolis, Minn.

Abstract. LW-negative (LWd red blood cells and anti-LW antibody were discovered in the blood of a 50-year-old white male with Hodgkin’s disease and blood type 0. Compatible red blood cells for transfusion could not be obtained because available LW-negative cells were either type A, LW,, or type 0, LWs. Following cytotoxic therapy for his basic disease, the anti- LW disappeared and his red blood cells developed normal reactions with anti-LW sera.

to

Introduction

Transient conversion of red blood cells an LW-negative status, associated with

the presence of anti-LW in the serum, has been reported in only four previous cases [l, 31, all in women, and three of them as- sociated with pregnancy. This phenomenon has now been noted in a male seriously ill with Hodgkin’s disease. The serologic find- ings in this case reverted to normal after cytotoxic therapy for his basic disease.

Case History

ERD, a 50-year-old white male, was admitted to the University of California Medical Center in January, 1973, because of abdominal pain, weight

1 Supported in part by grant No. CA15182 from the Department of Health, Education, and Welfare.

loss and night sweats. His past history revealed that he had been transfused during surgery for shrapnel wounds in World War I1 with no known complications. His present illness began in March, 1972, when he was seen at another hospital be- cause of vague abdominal pains, weight loss and anemia. Surgery was planned when a cholecysto- gram revealed multiple gall stones, but was can- celed when his serum was found to have an anti- body reacting with all other available red cells. His blood was referred for further studies to the Irwin Memorial Blood Bank of the San Francisco Medical Society, to the Philip Levine Laboratories, and to the University of Minnesota. All agreed that the antibody specificity was anti-LW, and that his cells were LW-negative.

On admission to the University of California hospital, laboratory data were as follows: hemo- globin 7.5 g/dl, hematocrit 26%’ RBC 3,400,000/~1, reticulocytes 0.3%, WBC 13,900Ip1 (83% PMN), total bilirubin 0.4 mg/dl, haptoglobin greater than 300 mg/dl, serum hemoglobin less than 5 mg/dl, LE cells not found, and stool benzedine 2+. X-rays revealed ’ a paraspinal mass. Attempts were made to obtain compatible blood for surgery by contact-

300 Perkins/McIlroy/Swanson/Kadin

ing the rare donor files of the American Associa- tion of Blood Banks, the American National Red Cross, the Canadian Red Cross and the World Health Organization list. No LW-negative donors were uncovered which were not already known to the participating laboratories. Of the seven known potential donors, three were ABO-incom- patible and four were incompatible with the pa- tient’s anti-LW. A further fall in hemoglobin prompted emergency exploration without trans- fusion. Biopsy of a retroperitoneal mass revealed Hodgkin’s disease, mixed cellularity type. Chemo- therapy was begun with Cytoxan, Oncovin and Procarbazine. A partial clinical response resulted, and by May, 1973, his hematocrit was greater than 30%. He was then encouraged to donate a unit of red cells for frozen storage. In July, 1973, a second unit of red cells was donated. At this time, tests at the Reference Laboratory Conference of the American Association of Blood Banks and in all of the participating laboratories found the patient’s cells to type as LW-positive, and the anti-LW was no longer detectable. Abdominal pain and abnormal lymphangiograms persisted. Chemotherapy was repeated at intervals with a variety of agents. In February, 1974, he received 4,000 r of irradiation to the abdomen, and in July, 1975, was given local irradiation for a painful des- tructive right iliac bone lesion. At this point his hematocrit fell to 19%, and three units of packed cells were easily cross-matched and uneventfully transfused, with an appropriate rise in hematocrit.

Results

ERD red cells were typed 0, R,r. They were found to be LW-negative in August, 1972, and again in January, 1973. They were nonreactive with available samples of anti-LW, including Van der Wyst, Cairy, Waldner, Carruthers, Bigelow, Delbl and Krumsick.

Table I illustrates the results with the patient’s antibody. Reactions were stronger with Rh-positive red cells than with Rh- negative red cells. In the antiglobulin phase,

patient cells were microscopically reactive with his own serum, but the direct antiglob- ulin test was positive to the same extent. An ether eluate was nonreactive on one oc- casion. On repetition, there was a very weak reaction at the antiglobulin phase with Rh- positive cells only.

When patient serum was retested after a single absorption with rr cells, the antiglob- ulin reaction with Rh-positive cells was reduced from 4+ to 2+ and with Rh-negative cells from 2+ to 2 .

Table I1 shows the results when ERD serum was tested with LW-negative cells. The three type 0, LW-negative cells have been classified as LW, and were incompat- ible; the three type A, LW-negative cells have been classified as LW., and were com- patible, as were the an,,,, cells.

In May and again in July, 1973, samples from this same donor were LW-positive with all of the LW sera with which his cells initially failed to react. Cryopreserved cells taken from the patient in January, 1973, tested simultaneously, were LW-negative. By April, 1973, no unexpected antibodies could be detected in the patient’s serum, and the direct antiglobulin test was nega- tive.

Discussion

Anti-LW has been found in four differ- ent situations. It may occur as an early re- sponse to immunization with Rh-positive cells in normal D-negative individuals [l], as an autoantibody in warm autoimmune hemolytic anemia [ 111 , as an alloantibody in genetically LW-negative individuals, or as a transient antibody in transiently LW- negative individuals [ 1,3, present report].

Transient LW-Negative Red Blood Cells and Anti-LW in a Patient with Hodgkin's Disease 301

Table I. Reactions of ERD's antibody with group 0 red cells

Temperature Method Detection Rh+ Rh - Auto cells cells cells control

4 "C RT 31 "C

~

saline + + + high protein f f high protein + + + AHG + + + + + + + + f

- - - -

~

RT = Room temperature.

Table JI. Reactions of ERD serum with LW-negative red cells

LW-Negative RBC ABO Rh LW Reactions of serum ERD

Waldner Vanek2 McKay4 Bigelow Bachtell Delbl Turgeon Harris A tterberry

0 0 0 A5 A A

+ +' + +3 + +3 -1, 3

-3

-1, 3

-3

-3

-3

- =Negative reaction. Tested in Minneapolis. LE-negative during pregnancy. Became LW-positive after delivery. Tested in Raritan. LW-negative during pregnancy. Remained LW-negative 6 months postpartum. The anti-A was absorbed from the patient's serum prior to tests with type A cells.

Transient appearance of LW-negative red cells at a time when anti-LW is present in the same blood suggests that the LW antigens are unaltered but are blocked by autoantibody to the action of other anti-LW sera. If this were the case, a positive direct antiglobulin test would be expected when- ever the cells test LW-negative. Although three of the four previous cases did have positive direct antiglobulin tests, case 2 of Chown et al. [l] did not at any time, nor

did their case 1 when first found to be LW- negative [l]. The present case adds further evidence that the negative reactions with anti-LW sera are not a result of blocking by autoantibody. The direct antiglobulin test was positive only microscopically, and it seems unlikely that blocking could have resulted from the minimal amount of anti- body which could be eluted. There was no laboratory evidence of hemolysis.

Reactions of the patient's anti-LW pro-

302 Perkins/McIlroy/Swanson/Kadin

vide further support for the heterogeneity of the LW-negative status [lo, 121. Red blood cells have been classified according to the amount of LW antigen they contain. Nor- mal Rh,(D)-positive cells have the most LW antigen, and are classified as LW,. Nor- mal Rh-negative cells have less LW antigen and are classified as LW,. The LW-negative patients fall into two groups: LW, and LW, based on the fact that the anti-LW in the sera of LW, patients reacts with the cells of the LW, category. The patient reported above would be classified as an LW,, since his serum reacted with all LW, cells and his cells did not react with ahy sera con- taining anti-LW. The reactions of his serum with LW, cells contraindicated transfusions from those donors, and all of the LW, do- nors were ABO-incompatible, making it im- possible to transfuse him.

All previous cases of transient LW-neg- ative red cells with anti-LW have occurred in females, three being associated with preg- nancy, and the fourth having a history of prior transfusion. The patient described above was male, but did also have a history of prior transfusion. Since there was no evidence of any reactions at that time, it is likely that he did not then have anti-LW in his blood. His LW-negative red cells and his anti-LW were discovered when he had ad- vanced Hodgkin’s disease, and the serolog- ical phenomena reverted to normal with multiple drug cytotoxic therapy for his dis- ease. Although this suggests the possibility that the serologic findings are related to Hodgkin’s disease, it should be remembered that all of the other cases reverted to nor- mal spontaneously.

The association of these findings with Hodgkin’s disease thus remains debatable, but there have been a number of observa-

tions suggesting that patients with Hodg- kin’s disease can develop changes in their red cell antigens and antibodies. Scott and Rusbridge [a] reported a case in which a previously normal type A blood developed the reactions of A, blood, associated with weakening of the H and I antigens and an increase in reactivity to anti-i. These abnor- malities reversed somewhat after therapy for Hodgkin’s disease. Gurrutty et ul. [2] have reported four cases of Hodgkin’s dis- ease who produced an unusual red cell anti- body with anti-IT specificity. The antibody was of the IgG class reacting optimally at 37 “C in each case. In three of the cases, it reacted as an autoantibody, resulting in he- molysis.

Aberrations of cellular immunity also occur in Hodgkin’s disease and are far more common than these serological phenomena. There is evidence of increased IgG synthe- sis by the spleen of patients with Hodgkin’s disease and this IgG has been shown to bind to peripheral blood lymphocytes [7]. IgG can be eluted from these lymphocytes, and may interfere with their normal immunolog- ic function [4]. IgG has also been shown to be associated with the Reed-Sternberg cell [5 ,6 ] , the characteristic cell of Hodgkin’s disease. It is not yet clear whether this im- munoglobulin is made by the cell or directed against it.

The phenomenon of transient disappear- ance of LW antigens with concomitant ap- pearance of anti-LW remains unexplained. It has been associated with pregnancy, transfusion and now with Hodgkin’s disease. Hodgkin’s disease, as already noted, has been associated with weakening of other red cell antigens and unusual antibodies. Preg- nancy may result in marked weakening of Lewis and Sda antigens. The consistent

Transient LW-Negative Red Blood Cells and Anti-LW in a Patient with Hodgkin’s Disease \ 303

appearance of anti-LW in cases with tran- sient loss of LW antigens was preceded by pregnancy or recent transfusion in all pre- viously reported cases. In the present case, however, the 30-year interval between transfusion and the recognition of the anti- LW casts great doubt on the role of trans- fusion in producing this antibody. It is con- ceivable, of course, that LW antigens disap- pear in a variety of relatively common cir- cumstances, and that the only cases which come to our attention are those in which anti-LW occurs, resulting in incompatible cross-match tests.

While preparing this paper we have been told of several cases of the same or similar phenomena, i.e., patients apparently losing LW antigens and simultaneously producing anti-LW. In some of the cases, tests during remission were not done, so there is not proof that they are not genetically LW-neg- ative. However, in more than 10 cases diag- noses such as lymphoma, leukemia, sar- coma, ‘cancer’ and ‘malignancy’ predomi- nate [9].

References

Chown, B.; Kaita, H.; Lowen, B., and Lewis, M.: Transient production of anti-LW by LW- positive people. Transfusion 11: 220-222 (1971). Garratty, G.; Petz, L. D.; Wallerstein, R. O., and Fudenberg, H. H.: Autoimmune hemolytic anemia in Hodgkin’s disease associated with anti-IT. Transfusion 14: 226-231 (1974). Giles, C. M. and Lundsgaard, A.: A complex serological investigation involving LW. VOX Sang. 13: 406-416 (1967).

4 Grifoni, V.; Del Giacco, G. S.; Manconi, P. E.; Tognella, S. and Mantovani, G.: Lymphocytes

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7

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9 10

11

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in spleen in Hodgkin’s disease. Lancet i: 322- 333 (1975). Kadin, M. E.; Gold, S. B.; Garratty, E. M., and Stites, D. P.: Immunological membrane markers of Hodgkin’s cells; in Neth, Gallo, Mannweiler and Moloney, Modem trends in human leukemia 11, pp. 229-236 (J. F. Leh- manns Verlag, Munich 1976). Leech, J.: Immunoglobulin-positive Reed-Stern- berg cells in Hodgkin’s disease. Lancet ii: 265- 266 (1973). Longmire, R. L.: McMilland, R.; Yelenosky, R.; Armstrong, Samuel; Lang, J. Eugene, and Craddock, Charles G.: In vitru splenic IgG syn- thesis in Hodgkin’s disease, New Engl. J. Med. 289: 763-766 (1973). Scott, G. L. and Rasbridge, M. R.: Loss of blood group antigenicity in a patient with Hodgkin’s disease. Vox Sang. 23: 458-460 (1972). Stroup, M.: In preparation. Swanson, J. L.; Azar, M.; Miller, J., and McCullough, J. J.: Evidence for heterogeneity of LW antigen revealed in a family study. Transfusion 14: 470-473 (1974). Vos, G. H.; Petz, L. D.; Garratty, G. G., and Fudenberg, H. H.: Autoantibodies in acquired hemolytic anemia with special reference to the LW system. Blood 42: 445-453 (1973). White, J. C.; Rolih, S.; Wilkinson, S. L.; Hatcher, B. J., and Issitt, P. D.: A new ex- ample of anti-LW and further studies on heterogeneity of the system. Transfusion 15: 368-372 (1975).

Received: December 6,1976 Accepted: February 7,1977

Herbert A. Perkins, MD, Irwin Memorial Blood Bank of the San Francisco Medical Society, 270 Masonic Avenue, San Francisco, CA 94118 (USA)