RELATIONSHIP BETWEEN HUMORAL AND CELLULAR ISOANTIBODIES. I. INABILITY OF HUMORAL ISOANTIBODIES TO PREVENT THE CYTOTOXIC EFFECT OF IMMUNE LYMPHOCYTES.
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Antibodies↗
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[IN VITRO AND IN VIVO STUDY OF THE CYTOTOXIC EFFECT OF "CELLULAR" AND HUMORAL ISOANTIBODIES. I. CYTOTOXIC EFFECT OF HUMORAL ISOANTIBODIES FROM CELLS "RESISTANT" TO SARCOMA IN MICE].
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Animals↗
Blood group isoantibody stimulation in man by feeding blood group-active bacteria.
It was investigated whether or not the human blood group isoantibodies A and B could be induced by immunogenic stimuli via natural routes with a kind of antigenic substance to which all humans are commonly exposed, or if the appearance of these antibodies is independent of antigenic stimuli as has long been believed. Escherichia coli O(86), which possess high human blood group B and faint A activity in vitro, were fed to healthy humans and those with intestinal disorders. 80% of the sick individuals of blood group O and A responded with a significant rise of anti-B antibodies which was frequently de novo in infants; significant increase of anti-A isoantibodies among blood group O individuals was less frequent. Over one-third of the healthy individuals also had a significant isoantibody increase. Intestinal lesions favor isoantibody stimulation by intestinal bacteria; this view was supported by the study of control infants. Persons of blood group A responded more frequently with anti-B and anti-E. coli O(86) antibody production than those of blood group O. Isoantibody increase was accompanied with antibody rise against E. coli O(86). Inhalation of E. coli O(86) or blood group AH(O)-specific hog mucin also evoked isoantibodies. The induced isoantibodies were specifically inhibited by small amounts of human blood group substances. E. coli O(86)-induced anti-blood group antibodies in germ-free chickens and preexisting blood group antibodies in ordinary chickens were neutralized by intravenous injection of E. coli O(86) lipopolysaccharide. This study demonstrates that human isoantibodies A and B are readily elicited via physiological routes, by blood group-active E. coli, provided the genetically determined apparatus of the host is responsive. Antibodies against a person's own blood group were not formed. Interpretation of these results permits some careful generalizations as to the origin of so-called natural antibodies.
ABO Blood-Group System↗
Irregular isoantibodies in the sera of patients undergoing chronic hemodialysis.
We screened 89 patients undergoing chronic hemodialysis for irregular isoantibodies. Irregular isoantibodies were detected in six patients (6.7%). This is an extremely high percentage compared with previous reports, considering that the presence of irregular isoantibodies was estimated to be 2.91% in multiparas, in whom they were found most frequently. This may be due to the fact that hemodialysis patients often receive blood transfusions but it also suggests that hemodialysis per se may induce the production of irregular isoantibodies. The blood-group specificities of the irregular isoantibodies detected were anti-N, anti-Leb + anti-HI, anti-Lea + anti-Leb, anti-H and anti-I, anti-P1, anti-rh" (E). The majority of the cases with irregular isoantibodies were examined because of clinical problems during hemodialysis. Therefore, we checked for the presence of irregular isoantibodies before the induction of hemodialysis and every three to six months thereafter.
Adult↗
Detection of platelet isoantibodies by (3H)serotonin platelet release and its clinical application to the problem of platelet matching.
The detection of platelet isoantibodies by the release of (3H)serotonin from platelets has been evaluated. The conditions for optimal release of (3H)serotonin with platelet isoantibodies using a microtechnique have been defined. A group of cardiac surgery patients were followed pre- and post-transfusions, with 48percent developing a positive serotonin release assay. Of these patients, 16percent also had a platelet complement-fixing and/or lymphocytotoxic isoantibody. There was variation in the degree of correlation between (3H)serotonin release and lymphocytotoxicity using individual National Institutes of Health typing serum. The matching obtained between family members by both techniques showed a close correlation when each technique was evaluated separately using the same NIH typing serum. The detection of iso-antibodies in patients with hematological malignancies correlated with the unresponsiveness to unmatched platelet transfusions in 15 out of 17 cases. The use of the patient's isoantibody to matched platelets of family members by (3H)serotonin release correlated well with the clinical response to transfusion with these platelets. The data suggest that (a) platelet isoantibodies can be detected with increased frequency by (3H)serotonin release; (b) (3H)serotonin release is a specific reaction depending on the surface antigen of the platelet; and (c) the method can be used to match compatible family members for platelet transfusions.
Blood Donors↗
The detection of platelet isoantibodies by membrane immunofluorescence.
A membrane ummunofluorescence test for the detection of platelet isoantibodies is described. Gel filtration of the incubation mixture was incorporated in the procedure and proved effective for the removal of serum proteins from the platelet suspension. With this technique isoantibodies were found in the serum of 13 out of a group of 16 patients who had received multiple transfusions. The results were checked by measuring the uptake of 125I-labeled anti-IgG fraction by gel-filtered platelets. Subsequently the membrane immunofluorescence method was also compared with established techniques described for the detection of isoantibodies such as the microtest for lymphocytotoxicity and a complement-fixation method and the procedures based on the release of labeled serotonin, the phagocytosis of chromium-tagged platelets, the increase of platelet factor 3 activity, and on platelet aggregation. We had the opportunity to investigate the serum of one patient for the presence of isoantibodies against platelets from HLA identical siblings both before and after the administration of their platelets. On the basis of this experience it is concluded that the membrane immunofluorescence test for platelet isoantibodies is a relatively simple method with a high degree of specificity and adequate sensitivity.
Antibodies, Anti-Idiotypic↗
Lack of impact of ABO blood group or corresponding isoantibodies on the immune response after rabies vaccination.
Demand for rabies hyperimmunoglobulin has increased recently, requiring optimization of vaccination schemes for immunized plasma donors. Possible resemblance of rabies vaccine to blood group antigens and consequential association of the immune response to rabies vaccine and blood group or corresponding isoantibodies has not yet been investigated. We analyzed antirabies antibodies after rabies vaccination and ABO blood group in 142 individuals, and isoantibody titers in 92 of those individuals. We did not find any correlation of the immune response with blood group or isoantibody levels. There was also no correlation with the sex of individuals, but there was a weak correlation between age and rabies-specific antibody level. Rabies vaccination schemes for immunized donors cannot be optimized on the basis of blood groups or isoantibody titers.
ABO Blood-Group System↗
Quantitative studies of the sensitivity of normal and neoplastic mouse cells to the cytotoxic action of isoantibodies.
Experiments were performed to study the mechanisms of the sensitivity of normal and neoplastic mouse cells to the cytotoxic action of humoral isoantibodies. A quantitative in vitro absorption procedure was used to compare the residua] hemagglutinin titer of a certain isoantiserum after the absorption of a known volume with known cell numbers. The cell numbers were adjusted so as to yield the same average total cell surface area. Lymph node cells and various solid and ascites tumor cells of strain A and C3H origin were used. It was found that different cell types differed with regard to their concentration of isoantigenic surface receptors. High correlation coefficients were found between the cytotoxic sensitivity and the concentration of isoantigenic receptors. It was shown that tumor cells which were partially or completely resistant to a single isoantiserum could be made sensitive to humoral isoantibodies provided that they were treated with mixtures of antisera, produced in different donor genotypes against the same target genotype, since each individual genotype reacts against a different antigen combination. This supports the concept that cytotoxic sensitivity is related to the surface concentration of reactive sites. Hematopoietic liver cells of newborn mice, which are completely resistant to isoantibodies, and spleen and lymph node cells of adult animals which are highly sensitive, were compared with regard to their ability to take up fluorescein-conjugated normal mouse serum in vitro. No differences were found between their visible pinocytotic uptake. Similar experiments were performed with various ascites tumor cells having different cytotoxic sensitivity. All tumor cells studied had a low pinocytosing ability which was not correlated to their sensitivity to humoral isoantibodies.
Animals↗
Life-threatening adverse reaction followed by thrombocytopenia after passive transfusion of fresh frozen plasma containing anti-CD36 (Nak) isoantibody.
BACKGROUND: Anti-CD36 isoantibody in blood recipients is reported to cause refractoriness to platelet (PLT) transfusions and posttransfusion purpura-like syndrome. There are few reports, however, about the effects of passively transfused blood products containing this isoantibody on recipients. CASE REPORT: A 67-year-old Japanese woman underwent brain surgery. On the 6th postoperative day, the patient experienced tightness of the chest and nausea after receiving a transfusion of fresh frozen plasma (FFP). When she manifested hypotension, the transfusion was discontinued. No cutaneous manifestation was observed. The patient's condition gradually improved soon after the administration of steroids. RESULTS: Her pretransfusion PLT count was 17.1 x 10(4) per microL. It decreased to 1.9 x 10(4) per microL 12 hours after transfusion and recovered to 15.4 x 10(4) per microL 8 days after transfusion. The donor of the FFP had a Type I CD36 deficiency. Flow cytometric analysis identified anti-CD36 isoantibody in the FFP. The cross-match between the patient's PLTs and the FFP was positive. The FFP induced the aggregation of PLTs derived from healthy adults. CONCLUSION: This is the first reported case of life-threatening adverse effects and thrombocytopenia caused by passively transfused anti-CD36 isoantibody. The possibility of passive infusion of this antibody should be considered in the evaluation of life-threatening transfusion reactions followed by thrombocytopenia.
Acute Disease↗
Pregnancy in mother with Glanzmann's thrombasthenia and isoantibody against GPIIb-IIIa: Is there a foetal risk?
Glanzmann's thrombasthenia (GT) is a rare autosomal recessive platelet disorder caused by qualitative or quantitative abnormalities of a platelet glycoprotein complex (GPIIb-IIIa) leading to excessive bleeding. Platelet transfusions are the first-line therapy for severe or persistent bleeding and surgery. Isoantibody against GPIIb-IIIa complexes present on normal platelets can be observed in Glanzmann's thrombasthenia type I patients after platelet transfusion possibly leading to platelet transfusion refractoriness. Pregnancy in Glanzmann's thrombasthenia type I women is rare, and severe bleeding can be observed in the peripartum or late postpartum period. Moreover, pregnancy can contribute to the maternal isoimmunization by the passage of the foetal cells into the maternal circulation. The transplacental passage of the maternal isoantibodies can induce moderate to severe foetal thrombocytopenia. We discuss here the case of in utero death at 31 weeks of gestation due to intracranial haemorrhage in an immunized mother and review the literature. Presence of isoantibody prior to gestation or detected during the index pregnancy must be taken into account in evaluating risk for the mother and the foetus.
Adult↗
Isoantibodies in immunoglobulin for intravenous use may cause erythrocyte sequestration.
BACKGROUND AND OBJECTIVES: IVIg, while generally a safe therapy for a variety of immunological disorders, can have detrimental effects on erythrocyte (RBC) homeostasis. We studied the mediation of erythrophagocytosis by isoantibodies in IVIg. MATERIALS AND METHODS: RBC were exposed to IVIg and binding of IgG determined by flow cytometry. In vitro phagocytosis of these RBC was assayed. RESULTS: Anti-A and anti-B in IVIg mediate Fc-dependent erythrophagocytosis even in the presence of excess IVIg. Removal of these isoantibodies from IVIg prevents IgG binding and erythrophagocytosis. Complement enhances IVIg-mediated RBC sequestration. CONCLUSION: It may be desirable to remove isoantibodies from IVIg especially for anemic patients or those who respond to the IVIg with a hemolytic episode.
Adolescent↗
[Detection and side effects of isoantibodies in intravenously administered immunoglobulin preparations].
BACKGROUND: Intravenous immunoglobulins (IvIg) contain not only the declared antibodies against pathogenic microorganisms, but also all the other antibodies of the blood donors, e.g. against erythrocytic antigens. MATERIALS AND METHODS: We tested 14 IvIg from 7 manufacturers (a total of 40 charges) for isoantibodies and irregular antibodies. To improve the reading of our tests we used the gel centrifugation method (ID-Microtyping-System, Fa. Diamed, Bensheim, Germany). RESULTS: The highest isoantibody titers were (in 8 charges) 1:32 or 1:64 in the Liss-Coombs test. Irregular antibodies were found in 5 IvIg (maximal titer 1:8). CONCLUSIONS: Isoantibodies in the IvIg can influence blood group serologic tests. With an example of a newborn who had received IvIg we point to the potential danger of misinterpretation of a positive direct antiglobulin test after administration of IvIg. Therefore we recommend to carry out the direct antiglobulin test before administration of IvIg and to examine all eluates after a positive direct Coombs test not only with 0 RBCs but also with A or B RBCs of the AB0 blood group of the patient.
ABO Blood-Group System↗
Characteristics of an antiluteinizing hormone isoantibody produced during gonadotropin induction of ovulation.
Production of an antihuman LH antibody was suspected in a woman with isolated LH deficiency who received human pituitary gonadotropin (hPG) to induce ovulation and who developed secondary drug failure associated with very high "serum LH' values. Binding of [125I]LH to various dilutions of the patient's serum was demonstrated by precipitation with polyethylene glycol or sheep antihuman immunoglobulin G (anti-IgG) but not by precipitation with sheep antihuman immunoglobulin M (anti-IgM). Unlabeled LH competitively displaced [125I]LH from a 1:200 final dilution of the patient's serum, and indicated a single class of binding sites with a binding affinity of 1.5 X 1011 M-1 and a binding capacity of 84 ng LH/ml serum. The isoantibody was reactive against antigenic determinants in hPG, LH, and hCG but not against human FSH. Further examination showed binding to the beta, but not the alpha, subunit of two LH preparations and to beta hCG. It is concluded that repeated administration of hPG to this patient with isolated LH deficiency evoked IgG isoantibody formation against the beta subunit of LH.
Adult↗
Immunologic aspects of leprosy as related to leucocytic isoantibodies and platelet aggregating factors.
The incidences of various iso- and autoantibodies in a random population of 112 unselected leprosy patients is presented. Low titers of leucocytic isoantibodies and platelet aggregating factor were detected in the sera of a variable number of such patients. The leucoisoagglutinins were found in 8% of the sera of tuberculoid as well as lepromatous leprosy patients, whereas the leucoisocytotoxins were detected in a larger percentage of the lepromatous (40%) as well as tuberculoid (28%) cases. The platelet aggregating factors (PAF) were positive in 51.2% and 45% of lepromatous and tuberculoid cases respectively. Of the 21 positive sera for PAF, the antiplatelet factor by antihuman globulin consumption test could be demonstrated only in 66.6% and 50% of lepromatous and tuberculoid sera respectively. To study the frequencies of these newly detected antibodies or antibody-like factor and to compare their occurrences with other well-documented autoantibodies present in the sera of leprosy patients: cryoglobulins, antinucleoprotein antibody and thyroglobulin autoprecipitin were also studied in the sera of the same population of leprosy patients. It has been observed that the simultaneous occurrence of all these auto- and isoantibodies in the serum of one patient is a rare phenomenon. Leucocytic and platelet counts of these patients having antibodies against leucocytes and platelets were found to be within normal limits. Accordingly, it is suggested that the low levels of antileucocyte antibody and antiplatelet factor are probably harmless to the hosts. On the other hand, it is postulated that these antibodies may act as enhancing factors by being specifically adsorbed on the lymphoid cells, thus rendering them unresponsive to mitogenic stimulus in vitro. From these studies it seems that leprosy, especially the lepromatous type, is associated with some of the serological features suggestive of an autoimmune aberration.
Antibodies, Antinuclear↗
[Haptoglobin type and isoantibodies (anti-A and anti-B)].
In 582 sera of blood donors of the groups A1, A2, B and 0 the Hp type as well as the anti-A or anti-B isoantibody titres respectively were determined. The frequency distribution of isoantibody titres in serum samples with different Hp-type were compared. As far as the numerical difference of distribution was concerned there was only one significant observation in the group of B alpha--titres of test persons with a different Hp-type. On the basis of these findings the following Hp-type/isoantibody relation can be established: low anti-A or anti-B titres respectively (approximately 1:8) will occur more frequently in persons with the Hp-type 1-1, higher titres (approximately 1:64) are to be found predominantly in persons with Hp2 genes. These findings are in accordance with other results, on the basis of which is was suggested that persons with Hp2 gene product have a higher immunogenic reactivity in comparison to type Hp 1-1.
ABO Blood-Group System↗
The management of dental extractions in cases of thrombasthenia complicated by the development of isoantibodies to donor platelets.
Two cases of thrombasthenia, a rare hereditary disorder of platelet function, are presented. The oral surgical and dental management of these cases is discussed in the light of the development of isoantibodies to transfused platelets in one of the cases and in another case encountered. The problems of obtaining donor platelets matched for platelet and HL-A antigens are discussed. Emphasis is placed on the use of local hemostatic measures and antifibrinolytic agents in the management of hemorrhage in this disorder and the avoidance of platelet transfusions as far as possible. Conservative dentistry and early preventive dental advice are considered desirable in order to avoid extractions.
Adolescent↗
Generation of mouse oocyte monoclonal isoantibodies: their effects and those of antisperm monoclonal antibodies on in vitro fertilization.
Monoclonal isoantibodies to mouse oocyte antigens were generated by modified hybridoma techniques similar to those described for mouse sperm monoclonals. Following isoimmunization with mouse oocytes and cell fusion, hybrid cells were cultured initially in a semi-solid medium containing methylcellulose. Seven to ten days after cell fusion about 350 hybrid clones were recovered for subculture. By an indirect immunofluorescence assay using frozen or fresh mouse oocytes, twenty hybridomas were shown to produce antibodies that bind to various oocyte components including antigens of the zona pellucida. However, they did not cross-react with mouse spermatozoa or lymphocytes. A system was established to evaluate whether monoclonal antibodies to gamete-specific antigens have any inhibitory effects on the fertilization of mouse oocytes in vitro. A monoclonal antibody against zona antigen(s), ME 56, was shown to block fertilization of mouse oocytes via the inhibition of sperm binding to the zona pellucida. On the other hand, three out of four antibodies reacting with mouse sperm acrosomes were also inhibitory to mouse in vitro fertilization, perhaps mainly due to the inhibition of sperm acrosomal reactions. Using a sodium dodecylsulfate gel/protein blot radioimmunobinding method, the molecular weight of zona antigen(s) that react with ME 56 was determined to be in the range of 95,000, whereas that of the acrosomal antigen(s) reacting with the fertilization-inhibiting antibody, MS 207, was about 30.000. The results of this preliminary study suggest that monoclonal antibodies to certain gamete antigens can be a valuable tool for the analysis of sperm-egg interactions during the fertilization processes.
Acrosome↗
Sperm-specific isoantibodies and autoantibodies inhibit the binding of human sperm to the human zona pellucida.
Heterologous antisperm antibodies induced by immunization with Freund's adjuvants are known to inhibit sperm-zona binding. We have tested whether spontaneously occurring sperm-directed isoantibodies and autoantibodies inhibit the binding of human sperm to the human zona pellucida. Zonae pellucidae were obtained from the ovaries of a woman of reproductive age undergoing surgery for uterine malignancy. Couples at risk for immunity to spermatozoa were screened for humoral antisperm antibodies by immunobead binding. Sera containing head-directed antibodies of IgA and/or IgG classes were selected for passive antibody transfer. Populations of spermatozoa exhibiting differing proportions of antibody-bound sperm were obtained by exposure of antibody-negative sperm of a fertile donor to untreated sera or sera depleted of head-directed antisperm antibodies by prior absorption. Each zona pellucida was challenged sequentially with two populations of sperm. an inverse relationship was found between the number of spermatozoa adherent to the zona and the proportion of sperm exhibiting binding of IgA or IgG immunoglobulins over the head, indicating that the presence of these antibodies in the acrosomal region of the sperm head inhibited their ability to attach to the zona pellucida.
Autoantibodies↗