Impaired Antibody Response to Intravenous Immunization in Sickle Cell Anemia

Pediat. Res. 6: 145-149 (1972) Heterophile antibody immunology sickle cell anemia spleen Impaired Antibody Response to Intravenous Immunization in Sickle Cell Anemia ALLEN D. SCHWARTZ1241 AND HOWARD A. PEARSON Department of Pediatrics, Yale University School of Medicine and Yale-New Haven Hospital, New Haven, Connecticut, USA Extract The spleen is essential for the formation of antibody in response to intravenously administered particulate antigen. Therefore, this splenic function was investigated in a number of children with sickle cell anemia. Following intravenous administration of 1.0 ml sheep red cells, heterophile antibody titers were determined at Q, 7, 14, and 21 days. One normal (Hgb AA), one sickle trait (Hgb AS), and two sickle-thalassemia (Hgb SSF) children had significant rises in heterophile titers with at least a 2-fold rise in 7 days and a minimum of 4-fold rise by day 14. This is comparable to responses of normal individuals previously reported. Five Hgb SS children had minimal antibody response with none having a rise in titer at 7 days. Three of these children had palpable spleens but no splenic visualization on scans. Two children received transfusions which restored splenic uptake of radiocolloid before antigenic challenge. These children also failed to form antibody. One child with sickle cell anemia received the same dose of sheep erythrocytes intramuscularly and had a significant antibody response comparable to normals. Speculation The defect of immunologic function in children with sickle cell anemia is similar to that described in asplenic individuals. This may be an important determinant of the increased susceptibility to infection in children with this disorder and their predisposition to overwhelming pneumococcal septicemia. important clinical implications. These children are unusually susceptible to overwhelming septicemia [8, 16], a predisposition also seen in the young, splenectomized child [2, 4-6, 10, 11]. The basis of susceptibility to this type of infection is not completely clear, but it is due, at least in part, to a failure of the spleen's unique role in clearing bacteria from the blood of the nonimmune individual [21]. Further, the spleen appears to be essential for the formation of antibody in response to small doses of intravenously administered particulate antigen [17, 18]. The immunologic capacity of children with sickle cell disease has been reported to be Introduction We recently reported [14] a state of impaired splenic reticuloendothelial activity ("functional asplenia") in children with sickle cell anemia. This defect was suggested by observation of the hematologic changes of splenic hypofunction, and was confirmed by an isotopic scanning technique using 99mTc-sulfur colloid. Functional asplenia was found to be reversible in some patients by transfusions of normal red cells sufficient to reduce the numbers of sickle cells below 50% [13]. The fact that the great majority of children with sickle cell disease have abnormal splenic function has 145 146 SCHWARTZ AND PEARSON Table I. Hemagglutination titers to sheep red blood cells Patient / 2 3 4 5 6 7 8 9 10 Diagnosis1 AA AS S-Thal S-Thal SS SS SS SS (transfused) SS (transfused) SS (intramuscular challenge) DayO Day 7 Day 14 MaxiDay 21 mum tube rise 1:7 1:7 1:7 0 1:7 1:56 1:112 1:14 1:22* 1:112 1:56 1:28 1:112 1:28 1:56 1:56 1:56 1:112 1:224 1:28 1:224 1:28 1:56 0 0 1:7 1:7 1:56 1:56 1:56 1:56 1:28 1:112 1:112 1:112 1:112 1:224 1:56 1:7 1:7 4 5 2 6 2 0 1 1 Serum heterophile titer was determined just prior to challenge and at weekly intervals for the following 21 days. Heterophile testing was performed in a conventional manner, utilizing a 2% suspension of washed sheep red cells added to serial dilutions of the patients' sera. After incubation at room temperature for 2 hr, the degree of agglutination was determined macroscopically. Results 2 4 ' A A : Normal hemoglobin. AS: Sickle trait. S-thal: Sickle-/3-thalassemia. SS: Homozygous hemoglobin S disease. normal; however, studies of their response to intravenous antigen have not been carried out. Therefore, this splenic function was investigated in a number of children with sickle cell anemia and functional asplenia, and in patients with other hemoglobin S disorders who had normally functioning spleens. Table I lists the heterophile titers on all of the patients studied. Figures 1 and 2 depict the rises in anti body titers compared with values obtained by others in normal individuals [17, 18]. In our studies, one normal child, one child with sickle trait, and two childrer with S-/J-thalassemia had significant increases in heter ANTIBODY INTRAVENOUSLY RESPONSE TO ADMINISTERED SHEEP RED CELLS 9 r Materials and Methods A total of 10 children, 2-15 years of age, were studied. Six of these had homozygous hemoglobin S disease (Hgb SS). Two adolescents, 13-15 years of age, did not have palpable spleens. They were presumably asplenic owing to autoinfarction. The other patients with Hgb SS disease ranged in age from 2 to 6.5 years and had palpably enlarged spleens. The remaining subjects included one child with sickle trait (Hgb AS), one with normal hemoglobin (Hgb AA), and two siblings with sickle-/? (S-jS)-thalassemia (Hgb SSF). The nature of the study was explained in detail and informed parental consent was obtained in accordance with the provisions set forth in the Declaration of Helsinki. All of the children with Hgb SS disease, including those with palpable spleens, had no splenic uptake of the 99mTc-sulfur colloid. The two children with sickle-/Mhalassemia had uptake of the radiocolloid by their enlarged spleens demonstrated by scan. One milliliter of a 25% suspension of sheep erythrocytes in saline was administered intravenously to all subjects but one. The exception was a 3-year-old child with Hgb SS disease who received the same dose of sheep red cells by intramuscular injection. Transfusions of normal human red blood cells were administered to two of the children with Hgb SS disease. When the ability of the spleen to take up radiocolloid was established, they were challenged intravenously with sheep erythrocytes. ROWLEY'S NORMAL RANGE 7 14 21 DAYS FOLLOWING ADMINISTRATION OF SHEEP RBC Fig. 1. Antibody response to intravenously administered shee] red cells in control patients. S-thal.: Sickle-/3-thalassemia. HG) AS: Sickle trait. HGB SS: Homozygous hemoglobin S disease HGB AA: normal hemoglobin. Impaired antibody response in sickle cell anemia ophile titers. At least a 2-fold (1-tube) rise in heterophile antibody titer was seen by day 7, with a minimum of a 4-fold (2-tube) rise by day 14. These results are comparable to values obtained in normal individuals. The child with Hgb SS disease who received sheep erythrocytes intramuscularly also had a normal response. All five children with Hgb SS disease who received sheep red cells intravenously had minimal antibody response, fo (...truncated)