Retroviral-mediated transfer of the iduronate-2-sulfatase gene into lymphocytes for treatment of mild Hunter syndrome (mucopolysaccharidosis type II).
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Adult↗
Biomedical subjects
D F Stroncek
Publications and source records attributed to D F Stroncek.
Neutropenia in a patient receiving intravenous immune globulin.
A child with Guillain-Barre syndrome treated with intravenous immune globulin (IVIG) developed neutropenia (absolute neutrophil count = 390), which resolved 3 days after completion of the therapy. Potential mechanisms for the development of neutropenia during the use of IVIG therapy are discussed. In this case, testing of the IVIG used revealed the presence of a high concentration of anti-neutrophil antibodies compared to other samples. It is recommended that white blood cell and neutrophil counts be monitored daily during the use of such therapy.
Autoantibodies↗
Analysis of the expression of NB1 antigen using two monoclonal antibodies.
BACKGROUND: Neutrophil-specific antigen NB1 is expressed on neutrophil subpopulations in 97 percent of healthy individuals and is located on 56- to 64-kDa glycoprotein. While the molecule carrying NB1 has been identified, the nature of the NB1 epitope has not been well characterized. STUDY DESIGN AND METHODS: Two monoclonal antibodies (MoAbs), 1B5 and the recently produced 7D8, and four alloantibodies, all specific for NB1, were used to investigate the expression of NB1 on neutrophils from several donors. RESULTS: MoAb 7D8 was shown to be specific for NB1. It reacted with NB1-positive neutrophils from 52 donors in the granulocyte immunofluorescence assay and did not react with NB1-negative neutrophils from 8 donors. MoAb 7D8 immunoblotted a 56- to 64-kDa molecule on neutrophils from eight NB1-positive donors and did not react with this molecule on NB1-negative neutrophils from two donors. When 7D8 was tested in the monoclonal antibody immobilization of granulocyte antigens assay, it reacted with two NB1 alloantibodies, but not with NA1 or NA2 alloantibodies. To determine if MoAbs 7D8 and 1B5 recognized the same epitope, both were tested against the same NB1-positive neutrophils and the cells were analyzed by two-color flow cytometry. Both antibodies bound independently to neutrophils, which indicated that the antibodies recognized different epitopes. When similar studies were performed with MoAb 7D8 and three NB1 alloantibodies, 7D8 partially inhibited the binding of two of the alloantibodies. The size of the NB1-positive subpopulation was analyzed in 25 people using flow cytometry with both MoAbs and three alloantibodies. The subpopulation of antigen-positive cells was similar in all donors when 7D8 and the three NB1 alloantibodies were tested; however, the subpopulation recognized by MoAb 1B5 was smaller in two of the donors. Neutrophils from one of these people were analyzed by immunoblotting, and no differences were detected in the molecule carrying NB1 in those neutrophils and that molecule in control neutrophils. CONCLUSION: NB1 specificity is made up of at least two separate epitopes. The expression of NB1 varied among antigen-positive individuals. While NB1 is expressed by a 56- to 64-kDa glycoprotein, the structure of this protein on antigen-negative cells has not been determined.
Animals↗
Chloramphenicol-dependent antibody: a case report.
BACKGROUND: Chloramphenicol-dependent antibodies are a rare cause of interference in pretransfusion serologic testing. Their presence can be confirmed by the testing of red cells in both the presence and absence of chloramphenicol. CASE REPORT: A 29-year-old, group A, Rh-positive man with no history of chloramphenicol exposure was found to have a chloramphenicol-dependent panagglutinin in his serum. The antibody was IgM with a titer of 8. It showed no blood group specificity when tested with common and rare red cell phenotypes, and it failed to react with platelets and granulocytes. Confirmation attempts using a chloramphenicol sodium succinate solution as the cell-suspending medium led to negative results. The antibody reacted serologically only in the presence of chloramphenicol, which arises from the succinate derivative by the action of blood esterases. CONCLUSION: This case is an additional example of a chloramphenicol-dependent antibody. It demonstrates how the laboratory investigation of drug-related phenomena is dependent on testing the drug from that reacts in vivo.
Adult↗
Serologic evidence that factor IX inhibitor in the plasma of hemophilia B patients detects factor IX on normal red cells.
BACKGROUND: Patients with hemophilia B lack factor IX (F IX). These patients may become alloimmunized after the transfusion of F IX concentrates and may develop F IX inhibitors, which have been characterized as polyclonal IgG4 alloantibodies. Two cases in which F IX inhibitors caused difficulty in compatibility testing and antibody identification were encountered. It was hypothesized that, because F IX is present in normal plasma, it might be adsorbed by red cells in vivo and then be detected during antibody screening tests with serum containing F IX inhibitors. CASE REPORT: Sera from two African American half-brothers with hemophilia B were incompatible with all common and rare red cell phenotypes tested in the anti-human globulin test, but did not react with each other's red cells. The brothers' red cell antibodies were neutralized with both normal plasma and a commercially available F IX concentrate, which indicated that the red cell incompatibility was most probably caused by their F IX inhibitors. Red cells from an unrelated patient with hemophilia B and a very low titer of F IX inhibitor were tested against the half-brothers' sera and did not react. The compatible red cells from one of the half-brothers and the unrelated patient with hemophilia B adsorbed F IX from normal plasma or F IX concentrate after 37 degrees C incubation; this rendered them incompatible with the plasma containing F IX inhibitor from the other half-brother. CONCLUSION: F IX appears to be present on normal red cells and may be detected during compatibility and antibody identification procedures when serum or plasma containing F IX inhibitors is tested.
Adolescent↗
Changes in blood counts after the administration of granulocyte-colony-stimulating factor and the collection of peripheral blood stem cells from healthy donors.
BACKGROUND: After the collection of granulocyte-colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cells from healthy donors, the donor platelet counts fall. However, the magnitude and duration of this decrease are not known. STUDY DESIGN AND METHODS: Sixty healthy people were given G-CSF (5, 7.5, or 10 micrograms/kg/day) for 5 days (Days 1-5), and 1 peripheral blood stem cell component was collected on Day 6. The platelet count, white cell count, absolute neutrophil count, hematocrit, and red cell count were measured before administration of G-CSF (Day 0), before collection of peripheral blood stem cells on Day 6, and on Days 8, 10, 13, 16, and 20. RESULTS: The platelet count fell from 261 +/- 47 x 10(9) cells per L on Day 0 to 159 +/- 30 x 10(9) cells per L on Day 8 (p < 0.0001) and reached its lowest level on Day 10 (146 +/- 30 x 10(9)/L; p < 0.001). Compared to Day 0 levels, the platelet count was lower on Day 13 (185 +/- 49 x 10(9)/L, p < 0.001), was the same on Day 16 (270 +/- 53 x 10(9)/L), and was greater on Day 20 (333 +/- 60 x 10(9)/L, p < 0.0001). The white cell count returned to pretreatment values on Day 13, and the absolute neutrophil count returned to pretreatment values on Day 10 (Day 0 white cell count = 6.05 +/- 1.59 x 10(9)/L and Day 0 absolute neutrophil count = 3.97 +/- 1.52 x 10(9)/L). On Day 20, both were less than pretreatment values (white cell count = 5.14 +/- 1.24 x 10(9)/L, p = 0.0007 and absolute neutrophil count = 3.20 +/- 1.24 x 10(9)/L, p = 0.0036). The red cell counts on Day 16 (4.52 +/- 0.41 x 10(12)/L) and Day 20 (4.42 +/- 0.39 x 10(12)/L) were less than Day 0 values (4.73 +/- 0.43 x 10(12)/L, p = 0.008 and p < 0.0001, respectively). The hematocrit on Day 20 (39.2 +/- 3.2%) was also less than that on Day 0 (41.2 +/- 4.8%; p = 0.01). The changes in these blood counts were not affected by the dose of the G-CSF. CONCLUSION: After stimulation with granulocyte-colony-stimulating factor and the collection or peripheral blood stem cells, the platelet counts in normal donors were decreased for at least 7 days (Days 6-13). Two weeks after collection of peripheral blood stem cells (Day 20), platelet production was increased, but the production of neutrophils and red cells was decreased. If two or more peripheral blood stem cell components are collected, then the platelet count should be measured after the second and subsequent collections. Further studies on the long-term effect of G-CSF on blood counts are needed.
Adult↗
Treatment of normal individuals with granulocyte-colony-stimulating factor: donor experiences and the effects on peripheral blood CD34+ cell counts and on the collection of peripheral blood stem cells.
BACKGROUND: Granulocyte-colony-stimulating factor (G-CSF) has been used in patients to increase the level of circulating hematopoietic progenitors. Although G-CSF has been administered to some healthy individuals, the kinetics of mobilization of peripheral blood stem cells (PBSCs), the optimum dose schedule and the incidence and nature of adverse reactions in normal individuals are not completely defined. STUDY DESIGN AND METHODS: Normal individuals (n = 102) who received G-CSF for 5 or 10 days at doses of 2, 5, 7.5, or 10 micrograms per kg per day were studied. The subjects were observed for symptoms and physical changes, and blood samples were obtained for a variety of laboratory tests. After 5 or 10 days of G-CSF treatment, PBSCs were collected by apheresis and analyzed. RESULTS: Overall, 89 percent of the individuals completed the 5-day treatment protocol and 88 percent completed the 10-day protocol without modification of the dose of G-CSF administered. Ninety percent of donors experienced some side effect of G-CSF. The most frequent effects noted were bone pain (83%), headache (39%), body aches (23%), fatigue (14%), and nausea and/or vomiting (12%). The dose of G-CSF administered directly affected the proportion of people with bone pain (p = 0.025) or body aches (p = 0.045) or who were feeling hot or having night sweats (p = 0.02) or taking analgesics (p = 0.01). With the 5-day dose schedule, several changes in serum chemistries occurred, including increases in alkaline phosphatase (p = 0.001), alanine aminotransferase (p = 0.0013), lactate dehydrogenase (p = 0.0001), and sodium (p = 0.0001). Decreases occurred in glucose (p = 0.045), potassium (p = 0.0004), bilirubin (p = 0.001), and blood urea nitrogen (p = 0.0017). In donors who received G-CSF for 5 days, the absolute neutrophil count was increased after one G-CSF dose, and it reached a maximum on Day 6, as did the number of CD34+ cells (64.6 +/- 55.9 x 10(6) cells/L). In those same donors, the platelet count after apheresis on Day 6 was 32 +/- 13 percent lower than pretreatment values (250 +/- 42 x 10(9) cells/L). In donors receiving G-CSF for 10 days, the neutrophil count reached a maximum on Day 8, but the number of CD34+ cells peaked on Day 6 (58.3 +/- 52.1 x 10(5) cells/L) and then declined. The platelet count decreased from pretreatment values by 28 +/- 12 percent prior to apheresis on Day 11. When individuals were treated for 5 days with G-CSF, the quantity of CD34+ cells collected was directly related to the G-CSF dose. When 5 micrograms per kg per day was given, 2.80 +/- 1.81 x 10(8) cells were collected, compared with collection of 4.67 +/- 3.11 x 10(8) cells when 10 micrograms per kg per day was given (p = 0.04). More important, PBSCs collected after 10 days of G-CSF administration (5 micrograms/kg/day) had significantly fewer CD34+ cells (0.82 +/- 0.37 x 10(8) cells, p = 0.01) than did PBSCs collected after 5 days of G-CSF (5 micrograms/kg/day). CONCLUSION: Most normal donors receiving G-CSF experience side effects, but these are mild to moderate in degree. Some alterations in blood chemistries occur, but none were clinically serious. Because of the symptoms associated with G-CSF, these individuals must be monitored closely. The treatment of normal donors with G-CSF for more than 5 days significantly decreased the number of circulating CD34+ cells and the quantity collected by apheresis.
Adult↗
Concentration of citrate anticoagulant in peripheral blood progenitor cell collections.
BACKGROUND: Peripheral blood progenitor cell (PBPC) collection by hemapheresis has become widely used in recent years. For anticoagulation during cytapheresis, citrate solutions, commonly ACD-A, are used, at a recommended anticoagulant-to-whole blood ratio of 1:11 to 1:12. Although the apheresis procedure is generally well tolerated, the most common patient complaints are attributable to transient hypocalcemia, which is a side effect of the citrate anticoagulant. Patients experiencing discomfort due to hypocalcemia are sometimes managed by a decrease in the flow rate of the anticoagulant. CASE REPORTS: Two cases are reported in which seemingly minor reductions in the anticoagulant: whole blood ratio appeared to cause gelation of freezing solution prepared from plasma that was collected in addition to PBPCs for use in the cryopreservation of cells. In both cases, the final ratio of citrate anticoagulant to whole blood was less than 1:12. Gelation occurred when plasma collected under these conditions was used to prepare freezing solution. CONCLUSION: The addition of heparin to this plasma, or the addition of ACD-A to correct the anticoagulant:whole blood ratio, prevented the gelation of freezing solution, which suggests that coagulation activation in the autologous plasma specimen was implicated in the subsequent gelation. During cytapheresis for PBPC collection, citrate-containing anticoagulants should be used at the recommended ratio of 1:12, or with more anticoagulant than usual. Tolerance for a reduced concentration of citrate may be more limited than is generally appreciated. When plasma is collected in addition to PBPCs, heparin should be added to both the cells and the plasma as soon as possible after the collection. Patients undergoing PBPC and stem cell collection should be given supplemental calcium, rather than less anticoagulant, to alleviate the discomfort associated with citrate.
Adult↗
Determination of ABO glycosyltransferase genotypes by use of polymerase chain reaction and restriction enzymes.
BACKGROUND: The molecular basis of red cell ABO group antigens has been determined. The genes encoding the group A and B glycosyltransferases and a nonfunctional group O transferase have been cloned and sequenced. All three genes were similar. When compared to the nucleotide sequence of the A gene, the O gene has a one-base deletion that leads to a frame shift and results in a nonfunctional protein. The B gene differs from the A gene at seven nucleotides. STUDY DESIGN AND METHODS: Techniques using polymerase chain reaction and restriction enzymes to determine ABO transferase genotypes from white cell DNA were modified. Nucleotide sequence differences within the genes were analyzed by the application of selected restriction enzymes. Restriction enzymes Asp718 and BstEII were used to analyze the genes at nucleotide 258, and BssHII and Kas I were used to analyze the genes at nucleotide 523. ABO red cell phenotypes were compared in 60 unrelated individuals with ABO transferase genotypes. The ABO phenotypes and genotypes of individuals from two different families were also analyzed to determine if this method could distinguish individuals who were homozygous for A or B transferase genes from those who were heterozygous. RESULTS: The phenotypes and genotypes were consistent for all unrelated individuals, and within the families, heterozygous individuals could be distinguished from homozygous individuals. Nevertheless, two individuals from one family were found to have a group A red cell phenotype, but when the transferase genes were analyzed at nucleotide 523 with enzymes BssHII and Kas I, both A and B transferase genes were detected. Further analysis of the transferase genes at nucleotide 700 by using restriction enzymes Alu I and Hpa II and those at nucleotide 793 by using enzyme BstNI found that both transferase genes in the two individuals were similar to the A transferase gene. CONCLUSION: An A allele of the group A glycosyltransferase was detected that had the same sequence as the B gene at nucleotide 523 but was identical to the A gene at positions 700 and 793. The identification of this variant gene makes genotyping at nucleotide 523 unreliable. However, analysis of the genes at other sites of nucleotide variation may accurately identify phenotypes.
ABO Blood-Group System↗
The chemical and immunoglobulin structural features necessary for reactions of quinine-dependent antibodies to neutrophils.
BACKGROUND: Previously described were three patients with quinine-dependent antibodies to neutrophils, platelets, and red cells who had episodic pancytopenia and renal failure. The nature of the antibody-drug-neutrophil interactions was investigated with sera from these patients. STUDY DESIGN AND METHODS: Sera from all three patients were tested against neutrophils in flow cytometry in the presence of several compounds related to quinine. IgG and Fab and F(ab')2 fragments were prepared from the serum of one patient and tested against neutrophils in flow cytometry and immunoprecipitation in the presence of quinine and related compounds. RESULTS: In flow cytometry, sera from all three patients plus quinidine reacted with neutrophils. Sera from Patients 1 and 3 reacted with neutrophils in the presence of cinchonidine (desmethoxy-quinine) and serum from Patient 3 also reacted with neutrophils in the presence of cinchonine (desmethoxy-quinidine). None of the sera reacted with neutrophils in the presence of chloroquine or primaquine. Serum from Patient 3 plus quinolinic acid, a tryptophan metabolite, reacted with neutrophils, but sera from the other two patients did not. Patient 3 serum plus tryptophan or another tryptophan metabolite, quinalidic acid, did not react with neutrophils. IgG from Patient 3 serum reacted with neutrophils in flow cytometry in the presence of quinine, quinidine, cinchonidine, cinchonine, and quinolinic acid. F(ab')2 fragments plus quinine or cinchonidine also reacted with neutrophils, but Fab fragments plus quinine did not. In the presence of quinine, Patient 3 IgG immunoprecipitated the 85- and 60-kDa molecules and F(ab')2 fragments immunoprecipitated the 85-kDa molecule. Patient 3 serum plus quinidine, cinchonidine, cinchonine, and quinolinic acid immunoprecipitated the 130- and 85-kDa molecules, but not the 60-kDa molecule. CONCLUSION: Quinine-dependent neutrophil antibodies often react with neutrophils in the presence of quinidine and related compounds. These reactions were mediated by the F(ab')2 domain of IgG.
Autoantibodies↗
Posttransfusion purpura following bone marrow transplantation.
BACKGROUND: Thrombocytopenia is a major cause of morbidity and hospital expense following bone marrow transplantation. Platelet transfusions in these patients are frequently complicated by the recipient's development of antibodies to HLA class I antigens. When these patients become refractory to the transfusion of HLA-matched platelets, the recipient's platelet antigen phenotype must be determined, to ensure that donor platelets will be phenotypically compatible. Cases of alloimmunization to HPA-1a and HPA-1b resulting in refractoriness to transfused platelets and the subsequent development of a posttransfusion purpura-like syndrome are reported. CASE REPORTS: In the first case, a 43-year-old woman with Stage IV infiltrating ductal breast cancer presented to the hospital for a transplant of autologous peripheral blood stem cells. After the transplant, her platelet count remained less than 10 x 10(9) per L, despite daily platelet transfusions, including HLA-matched platelets. Fourteen days following the transplant, her serum was found to contain anti-HPA-1a. Initially, the patient was refractory to the transfusion of HPA-1a-negative platelets, but after treatment with intravenous immunoglobulin, she had transient increases in posttransfusion platelet counts. She was also treated with a staphylococcal protein A immunoadsorption column and has not had any such subsequent refractoriness. Her genotype has been found, by use of allele-specific oligonucleotide hybridization with white cell DNA, to be HPA-1b/1b. The second case involved a 32-year-old woman with chronic myelogenous leukemia who received an unrelated-donor marrow transplant. Three years later, her CML recurred, and she was treated with interferon-alpha. Four months afterward, she experienced interferon-alpha-induced thrombocytopenia and the interferon therapy was discontinued. She received 12 platelet transfusions in 20 days, but none was effective. Antibodies specific for HLA antigens and HPA-1b were detected, and three HLA-matched, HPA-1b-negative apheresis platelet components were given, but without effect. Two days after treatment with methylprednisolone (1 g intravenously) and prednisone (2 mg/kg/day orally), her platelet count was 26 x 10(9) per L, and after 8 more days, it was 102 x 10(9) per L, without further transfusions. She was found to be homozygous for HPA-1a (HPA-1a/1a). CONCLUSION: Anti-HPA-1a and anti-HPA-1b can cause refractoriness to platelet transfusions in bone marrow transplant patients. Testing for platelet-specific antibodies should be considered in all patients who are refractory to HLA-matched platelets.
Adult↗
Hemolytic anemia and acute renal failure associated with temafloxacin-dependent antibodies.
Quinine-ingestion has been associated with immune-mediated recurrent pancytopenia, hemolysis, and renal failure. The structure of fluoroquinolone antibiotics is similar to the structure of quinine. Over a 3 month period, three patients at our institution developed hemolysis and renal failure following ingestion of the fluoroquinolone antibiotic temafloxacin. Two of the three patients required hemodialysis. Following withdrawal from the drug, the hemolysis resolved and the renal function eventually returned to normal in all three patients. One patient also had a transient mild thrombocytopenia. Sera from all three patients were tested for drug-dependent antibodies to red blood cells, platelets, and neutrophils. Temafloxacin-dependent red cell antibodies were detected in one patient, and temafloxacin-dependent red cell and neutrophil antibodies were detected in a second patient. No temafloxacin-dependent antibodies were detected in the third patient. Sera from all three patients were also tested for quinine and quinidine-dependent antibodies to red cells, platelets, and neutrophils. Sera from the patient without temafloxacin-dependent red cell antibodies reacted with red cells in the presence of quinine. These results suggest that, at least in some patients, the toxicities associated with temafloxacin are immune mediated.
Acute Kidney Injury↗
Treatment of alloimmune neonatal neutropenia with granulocyte colony-stimulating factor.
Despite numerous attempts to increase the neutrophil count of infants with alloimmune neonatal neutropenia, no therapy has been consistently effective. We describe two infants with alloimmune neutropenia who had a rapid and prolonged increase in neutrophil number after treatment with granulocyte colony-stimulating factor (G-CSF). Patient 1 had antibody directed against the neutrophil antigen NA2. He received three daily doses of G-CSF, and within 2 days his neutrophil count increased from 0.350 x 10(9) to 3.584 x 10(9)/L (350 to 3584/mm3). Despite cessation of treatment the neutrophil count remained in the normal range. Patient 2 had antibody to the neutrophil antigen NA1, and received six daily doses of G-CSF. Within 4 days his neutrophil count increased from 0.477 x 10(9) to 4.320 x 10(9)/L (477 to 4320/mm3) and remained in the normal range for 11 days after the last dose of G-CSF. We recommend that treatment with G-CSF be considered for selected infants with alloimmune neutropenia.
Follow-Up Studies↗
Identification of a new white cell antigen.
BACKGROUND: Antibodies to white cell antigens can cause alloimmune neonatal neutropenia, autoimmune neutropenia, and transfusion reactions. CASE REPORT: A full-term male infant developed a skin infection and was found to be neutropenic on his fourth day of life. He had a transient increase in his neutrophil count after treatment with intravenous immunoglobulin, but his neutrophil count was not consistently normal until he was 6 weeks old. Serum from the baby's mother reacted in a granulocyte immunofluorescence assay but not in a granulocyte agglutination assay. The mother's serum was tested in the granulocyte immunofluorescence assay against neutrophils from 103 healthy, unrelated people, and it reacted with cells from 66 percent of those people. The expression of SL correlated weakly with the expression of NA1 (r = 0.23; p = 0.02) and 5a (r = 0.20; p = 0.05) antigens. SL antigen expression on neutrophils was not associated with the expression of NA2, NB1, NB2, NC1, 5b, 9a, or Mart. The expression of SL on neutrophils from members of an extended family was analyzed, and the antigen was found to be inherited in an autosomal-dominant manner. Anti-SL also reacted with T-lymphocytes in a flow cytometry assay but did not react with red cells or platelets. No lymphocytotoxic antibodies were detected in the mother's sera. The anti-SL was tested against neutrophils in an immunoprecipitation and immunoblotting assay, but no molecules were identified. The neutrophil-specific antigens NA are located on Fc gamma receptor III (CD16). To determine if the SL antigen was also located on Fc gamma receptor III, anti-SL was also tested in a monoclonal antibody immobilization of granulocyte antigens assay. Anti-SL did not react with molecules recognized by CD16 monoclonal antibodies. CONCLUSION: A new white cell antigen SL, with a frequency of 66 percent, was identified on neutrophils and T-lymphocytes as a result of the evaluation of a case of neonatal alloimmune neutropenia. The molecule bearing the SL antigen was not identified in immunoblotting, immunoprecipitation, or monoclonal antibody immobilization of granulocyte antigens assays.
Adult↗
Neutrophil-specific antigen NB1 inhibits neutrophil-endothelial cell interactions.
Neutrophil-specific antigen NB1 is located on a 58 to 64 kd glycosyl phosphatidylinositol-linked plasma membrane glycoprotein. NB1 antigen can be detected on neutrophils from 97% of healthy volunteers, and NB1 antigen is expressed on subpopulations of neutrophils. Neutrophil subpopulations with varying functions have been described, and we hypothesize that NB1 antigen may play an important role in neutrophil function. We compared the function of NB1-positive and NB1-negative neutrophils obtained from several persons. There were no differences in the adhesion of NB1-positive and NB1-negative neutrophils incubated in C5a, N-formyl-Met-Leu-Phe (FMLP), phorbol myristate acetate (PMA), or buffer to type IV collagen, fibronectin, laminin, or polystyrene. However, the adherence to human umbilical vein endothelial cells (HUVEC) monolayers of unstimulated NB1-positive neutrophils was less than to NB1-negative neutrophils (20.0% +/- 4.2% vs 31.7% +/- 5.8%; p < 0.01). When neutrophils were stimulated with C5a, PMA, or FMLP, no differences were found in the adhesion of NB1-positive and NB1-negative cells to the same surfaces. When NB1-positive neutrophils were incubated with rabbit polyclonal anti-NB1 Fab fragments, their adherence to HUVEC was increased (32.9% +/- 10.1% vs 18.3% +/- 5.0%; p < 0.05). Fab fragments prepared from normal rabbit serum had no effect on neutrophil adherence to HUVEC. The chemotaxis of NB1-positive neutrophils to FMLP through nitrocellulose was significantly greater than that of NB1-negative neutrophils (p = 0.03), but there was no difference in chemotaxis to FMLP through polycarbonate membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Antibodies↗
Recurrent pancytopenia, coagulopathy, and renal failure associated with multiple quinine-dependent antibodies.
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Acute Kidney Injury↗
Quinine-dependent antibodies to neutrophils react with a 60-Kd glycoprotein on which neutrophil-specific antigen NB1 is located and an 85-Kd glycosyl-phosphatidylinositol-linked N-glycosylated plasma membrane glycoprotein.
We have previously described a 24-year-old woman with quinine-dependent antibodies that reacted with neutrophils, red blood cells (RBCs), platelets, and T lymphocytes. The drug-dependent neutrophil antibody was found to react with 85- and 60-Kd neutrophil membrane molecules. In these studies, we further characterized these molecules and found that both were glycosyl-phosphatidylinositol (GPI)-linked and contained sialic acid residues and N-linked carbohydrate side chains, but neither contained O-linked carbohydrates. The protein backbone of the 60-Kd molecule was 45 Kd, and the 85 Kd glycoprotein (GP) was made up of 33- and 31-Kd proteins. While some GPI-anchored neutrophil GPs are released by stimulated neutrophils, neither the 85- nor the 60-Kd GP was released by neutrophil stimulated with C5a, f-met-leu-phe (FMLP), or phorbol myristate acetate (PMA). Neutrophil-specific antigen NB1 is located on a 58- to 64-Kd GP. To determine if the quinine-dependent antibody and anti-NB1 recognize the same GP, immunoprecipitation studies were performed with the quinine-dependent antibody using neutrophils with varying NB1 phenotypes. The 60-Kd GP was detected on NB1-positive neutrophils from 11 of 12 donors tested, but not on NB1-negative neutrophils from two donors tested. After solubilized 125I-labeled neutrophils were absorbed with anti-NB1, the quinine-dependent antibody immunoprecipitated the 85-Kd GP, but not the 60-Kd GP. These results indicate that anti-NB1 and the quinine-dependent antibody identified the same GP. The 85-Kd GP was detected on neutrophils from all 14 donors tested. The electrophoretic mobility of the 85-Kd GP was similar to the electrophoretic mobility of the major 125I-labeled neutrophil protein.
Adult↗
Experiences of the first 493 unrelated marrow donors in the National Marrow Donor Program.
More than 410,000 people participated in the National Marrow Donor Program (NMDP) as of October 1, 1991, and more than 850 volunteers had donated marrow. While the incidence of serious morbidity as a result of bone marrow donation is rare, the incidence of lesser complications and the long-term consequences of marrow donation are not known. To determine the incidence of donor complications and measure the recovery time of volunteer, unrelated marrow donors, we analyzed the results of surveys of the first 493 persons who donated marrow through the NMDP. The marrows were collected at 42 centers. The median age of the donors was 37.9 years (range 19.1 to 55.6 years). The median volume of marrow collected was 1,050 mL (range 180 to 2,983 mL). Autologous red blood cells were transfused to 89.8% (439) of donors but only 0.6% (3) of donors received allogeneic blood. Acute complications related to the collection procedure occurred in 5.9% of donors; but a serious complication, apnea during anesthesia, occurred in only one donor. When donors were questioned approximately 2 days following discharge from their hospitalization, most donors described symptoms related to the collection; 74.8% experienced tiredness, 67.8% experienced pain at the marrow collection site, and 51.6% of the donors experienced low back pain. Donors were surveyed repeatedly until they felt that they had recovered completely. Mean recovery time was 15.8 days; however, 42 (10%) donors felt that it took them > or = 30 days to recover fully. The duration of the marrow collection procedure and duration of anesthesia both positively correlated with donor pain and/or fatigue following the collection; but the duration of the collection procedure had the highest correlation with post-collection pain and fatigue. The volume of marrow collected per unit of donor weight was more weakly correlated with donor pain and/or fatigue than the anesthesia and collection times. When multivariate analysis was used to analyze the correlation between donor recovery time and these variables, only the duration of the collection was found to correlate significantly with donor recovery time (P = .001). This analysis demonstrates that marrow donation is well tolerated with few complications. To decrease further the incidence of donor discomfort and recovery time following donation, the duration of the collection procedure, and probably the duration of anesthesia, and the volume of marrow collected, should be kept to a minimum.
Adult↗