Frequency of alloantibodies accompanying autoantibodies

Blood samples of 109 patients with warm autoantibodies were evaluated for the presence of accompanying alloantibody. Clinically significant alloantibodies were present in 41, or 38 percent, of the cases.     

Evaluation of methods for detecting alloantibodies underlying warm autoantibodies

BACKGROUND: In pretransfusion testing of patients whose sera contain autoantibodies reacting optimally at 37°C, it must be determined whether alloantibodies are also present. Two approaches, testing a 1 -in-5 dilution of patients' sera and the adsorption of sera in the presence of polyethylene glycol (PEG), have been proposed as alternatives to the time-consuming approach of adsorbing sera with ficin- or ZZAP-treated red cells (RBCs). The three approaches were compared. STUDY DESIGN AND METHODS: Patients' sera containing warm autoantibodies, with and without alloantibodies, were retested 1) after dilution (1-in-5) and 2) after adsorption with allogeneic RBCs in the presence of PEG. Results were compared to those after adsorption with ZZAP-treated allogeneic RBCs. RESULTS: Dilution (1-in-5): Twenty-seven of 119 sera (7/26 [27%] with and 20/93 [22%] without alloantibodies) did not react; one example each of alloanti-D, -E, -e, -Fy^a, and -Jk^a, and two examples of anti-Jk^b were not detected at a dilution of 1 in 5. Alloantibodies were identified in 5 (19%) of 26 1-in-5 diluted sera containing alloantibodies; 87 (73%) of 119 sera still reacted with all cells and would have required further workup. PEG adsorption: Thirty-nine sera were tested after parallel PEG and ZZAP adsorptions. The PEG adsorptions required a total of 55 aliquots of adsorbing cells and 13.75 hours, whereas ZZAP adsorptions required 61 aliquots and 30.5 hours. All alloantibodies (anti-D [3], -C [2], -c [1], -E [4], -K [2], -Fy^a [1], -Jk^a[2], -Jk^b[1]) reacted in the adsorbed serum-PEG mixtures at a strength equal to or greater than that in the ZZAP-adsorbed sera. CONCLUSION: Although the 1-in-5 dilution approach is convenient, only 22 percent of warm autoantibodies without alloantibodies were nonreactive, and 27 percent of alloantibodies of potential clinical significance were not detected. PEG adsorption appears to give similar results to those of ZZAP adsorption, but it has the advantages of eliminating the cost and time of prior treatment of the allogeneic adsorbing cells and of a reduction of at least a 50 percent in adsorption time.     

Adsorption of autoantibodies in the presence of LISS to detect alloantibodies underlying warm autoantibodies

BACKGROUND: The safe transfusion of patients with warm autoimmune hemolytic anemia requires an efficient and time-saving assay to detect alloantibodies underlying autoantibodies. Methods used include RBCs treated with ZZAP reagent, proteolytic enzyme, or untreated RBCs in the presence of PEG. We propose a method using LISS, which presents some advantages over previous methods. STUDY DESIGN AND METHODS: We evaluated the effectiveness of autoantibody adsorption with papain-treated and untreated RBCs in the presence of LISS for removal of autoantibodies, without affecting alloantibodies. RESULTS: One-hundred twenty sera containing autoantibodies were adsorbed with our routine method, which uses papain-treated allogeneic RBCs. Seven-hundred twenty adsorptions (mean, 6 per sample) and 21,600 minutes (mean, 180 min per sample) were required to remove autoantibodies. Fifty sera were adsorbed with our routine method that uses papain-treated allogeneic RBCs in the presence of LISS. The number of adsorptions and the completion time were, respectively, 144 (mean, 2.9 per sample) and 2,880 minutes (mean, 57.6 min per sample). Twenty sera were evaluated with untreated autologous RBCs, in the presence of LISS; 58 adsorptions (mean, 2.9) and 1,160 minutes (mean, 58 min per sample) were required. Three adsorptions with antigen-negative allogeneic RBCs were performed on 8 sera containing alloantibodies with weak reactivity (anti-K [1], anti-D [1], anti-Fya[2], anti-S [2], anti-E [1], and anti-Jka[1]). Alloantibodies were detected with the LISS procedure with papain-treated and untreated RBCs and the routine papain method. Alloantibodies with weak reactivity, tested against the same antibody-detection RBCs, remained unchanged following adsorption of 5 sera. An anti-S, with very weak reactivity, was no longer detected, and an anti-Jka became weaker (1+), regardless of the procedure used. One anti-D became weaker only with the LISS adsorption method. CONCLUSION: Autoantibodies can be adsorbed more efficiently in the presence of LISS.     

PEG adsorption of autoantibodies and detection of alloantibodies in warm autoimmune hemolytic anemia

BACKGROUND: The purpose of this study was to evaluate the effectiveness of PEG in the adsorption of autoantibodies and the detection of alloantibodies in patients with warm autoimmune hemolytic anemia (WAIHA). STUDY DESIGN AND METHODS: The study was divided into three parts. First, the effectiveness of antibody removal by a conventional adsorption procedure and that by the PEG adsorption method were compared by using commercial antisera adsorbed with antigen-positive RBCs. Second, patients' sera with known weak alloanti-E were used to test against screening cells after allogeneic adsorption to show nonspecific coating of antibodies and the dilution effect on the PEG adsorption procedure. Third, conventional and PEG one-cell sample allogeneic adsorptions of WAIHA patients' sera with and without alloantibodies were performed and compared. RESULTS: In the first part, seven of the eight polyclonal antisera gave a lower titer and score when tested against antigen-positive RBCs in the indirect antiglobulin test; this indicated that PEG is more efficient in removing antibodies. In the second part, similar reaction patterns were observed in antibody screening tests on unadsorbed sera and on sera after the first, second, and third adsorptions, which indicated that there was no alloantibody loss, nonspecific antibody coating, or dilution effect when PEG was added in the allogeneic adsorption procedures. In the third part, a 40-percent increase in efficiency in reducing the number of adsorptions and an 85-percent decrease in completion time of the adsorption procedures were obtained when PEG was used for adsorbing sera from 16 patients with WAIHA. Both conventional and PEG procedures were capable of removing autoantibodies to identify the specificities of alloantibodies. CONCLUSION: The PEG adsorption method is an effective, sensitive, and efficient method of enhancing auto- antibody adsorption and alloantibody detection. It can reduce the processing time and minimize the delay of urgent transfusions to patients with WAIHA and can indirectly enhance cost-effectiveness and decrease the labor-intensive testing required by these cases.     

Coexistence of autoantibodies and alloantibodies to red blood cells due to blood transfusion

BACKGROUND: Autoantibodies (AUTO) to red blood cells (RBCs) are frequently associated with alloantibodies (ALLO). The mechanism for the coexistence of these antibodies is obscure. STUDY DESIGN AND METHODS: Between August 1998 and June 2006, all in- and outpatients of the Charité University Hospital, Berlin, with detectable AUTO were included in this study. Serologic examination was performed with standard techniques for the detection of RBC antibodies. RESULTS: A total of 717 patients were found to have AUTO, with ALLO observed in 200 of these patients (28%). The history of antibody production could be evaluated in 98 of the 200 patients. Both AUTO and ALLO were due to RBC transfusion in 73 cases (75%) and peripheral blood progenitor cell transplantation in 6 cases (6%). Nine (9%) patients were primarily alloimmunized and subsequently developed AUTO. The remaining 10 (10%) patients were primarily autoimmunized and later developed ALLO. Only 6 of these patients had chronic idiopathic autoimmune hemolytic anemia. CONCLUSION: The majority of AUTO associated with ALLO appears to be due to RBC transfusion that must be recognized as a major cause for autoimmunization.     

Clinical significance of RBC alloantibodies and autoantibodies in sickle cell patients who received transfusions

BACKGROUND: The clinical significance of alloimmunization to RBC antigens in sickle cell patients was analyzed by a retrospective review of the records of pediatric and adult sickle cell patients who received transfusions and who were followed over a 10-year period. STUDY DESIGN AND METHODS: Charts of pediatric and adult sickle cell patients followed at Schneider Children's Hospital (SCH) and Long Island Jewish Medical Center between 1989 and 1999 were retrieved. Patients followed at SCH were classified as pediatric, regardless of age. Data on transfusion history, alloimmunization, and transfusion reactions from 1990 were retrieved from computerized blood bank records. Transfusion history, development of alloantibodies and autoantibodies, and transfusion reactions were correlated with clinical evidence of hemolysis or other adverse reactions from the charts. All patients received ABO- and Rh-compatible blood transfusions for which a partial or extended antigen match was not performed. RESULTS: Among pediatric patients, 29 percent developed clinically significant alloantibodies, and 8 percent developed autoantibodies. Seven patients developed delayed hemolytic and/or serologic transfusion reactions, two with hyperhemolysis, two with clinical evidence of hemolysis, and three with serologic evidence only. The two patients with hyperhemolysis had received extended antigen-matched RBC transfusions to provide blood compatible with their existing antibodies. Among adult patients, 47.0 percent developed significant alloantibodies, and 9.7 percent developed autoantibodies. Five incidences of delayed hemolytic and/or serologic transfusion reactions occurred, one with hyperhemolysis and four with serologic evidence only. CONCLUSION: The alloimmunization rate is 29 percent in pediatric and 47 percent in adult sickle cell patients when partial or extended RBC antigen match is not performed. However, the delayed serologic and/or hemolytic transfusion reactions did not result in severe clinical outcome in most instances. The most important adverse event was hyperhemolysis, which may be triggered by a transfusion, but was not prevented by matching for RBC antigens. In most instances, the cause of hyperhemolysis was multifactorial.     

Lack of clinical significance of "enzyme-only" red cell alloantibodies

In a retrospective study on samples from 10,000 recently transfused patients, 35 samples were found to contain an antibody that reacted with ficin-treated red cells but was not demonstrable by low-ionic- strength saline solution and indirect antiglobulin test (LISS-IAT). In those 35 patients, the specificity of the antibody was such that each patient would have been transfused with antigen-negative blood had the antibody reacted in LISS-IAT. Tests on red cells from the units already transfused showed that 19 patients had among them received, by chance, 32 antigen-positive and 74 antigen-negative units. The remaining 16 patients had among them received 57 units that were, again by chance, all antigen negative. One patient given antigen-positive blood suffered a delayed transfusion reaction; in two others the antibodies became LISS-IAT active after transfusion. However, similar changes to the LISS- IAT-active state were seen with two antibodies of patients given only antigen-negative blood. Also found in the 10,000 patients were 28 clinically insignificant antibodies, 77 sera in which the antibody was too weak to identify, and 216 autoantibodies that reacted only with ficin-treated red cells. These data support a belief, generally held in the United States but not necessarily elsewhere, that the use of protease-treated red cells for routine pretransfusion tests creates far more work than the accrued benefits justify.     

Human platelet antigen-specific alloantibodies implicated in 1162 cases of neonatal alloimmune thrombocytopenia

BACKGROUND: Neonatal alloimmune thrombocytopenia (NATP) caused by fetomaternal mismatch for human platelet (PLT) alloantigens (HPAs) complicates approximately 1 in 1000 to 1 in 2000 pregnancies and can lead to a serious bleeding diathesis, intracranial hemorrhage, and sometimes death of the fetus or neonate. As a national reference center for NATP investigations, our experience with this entity over a 12-year period was reviewed. STUDY DESIGN AND METHODS: The laboratory records of all cases of suspected NATP referred for evaluation from January 1, 1990, to December 31, 2002, were analyzed. The spectrum of PLT alloantibody specificities identified was compared with an earlier reported series of serologically verified NATP cases. RESULTS: HPA-specific alloantibodies were identified in 1162 (31%) of 3743 sera of mothers of infants with clinically suspected NATP. Maternal HPA-1a (PlA1) alloimmunization accounted for the majority (79%) of confirmed NATP cases, with HPA-5b (Bra), HPA-3a (Baka), and HPA-1b (PLA2) alloantibodies accounting for 9, 2, and 4 percent of cases, respectively. In addition, an increase in the number of cases in which multiple HPA-specific alloantibodies were present in maternal sera was observed during the study period. CONCLUSION: Although, as with the earlier series, maternal HPA-1a alloimmunization was the dominant cause of NATP, the identification of an increasing number of cases due to alternative HPA polymorphisms suggests that investigation for HPA-1 incompatibility alone is no longer sufficient to fully evaluate clinically suspect NATP cases.     

Bronchogenic cyst appearing as a hepatic mass

Because bronchogenic cysts may be found in or near any organ derived from the embryonic foregut, they sometimes pose considerable diagnostic difficulties. We describe the plain chest X-ray, computed tomographic, and angiographic findings in a patient with elevated CA 19-9 and upper quadrant abdominal pain due to a cystic tumor appearing as a hepatic mass. Surgery and histology showed a bronchogenic cyst located in the lower lobe of the right lung.     

Two cases of Munchausen's syndrome presenting as acute respiratory distress

We present two cases of factitious disorder that presented as acute respiratory distress. The presentation was extreme to the point that the patients were intubated. Both patients were employed in an ancillary health care profession.     

385例癌患者自身抗体检测结果分析

目的：了解癌患者体内自身抗体阳性率、细胞内定位及荧光图形特点,初步确定自身抗体靶抗原本质,了解自身抗体与癌的相关性。方法：应用间接免疫荧光法（IIF）检测385例9种癌的患者以及140份不同年龄段正常人血清中自身抗体;以人喉癌上皮细胞（Hep-2)全面细胞裂解液为抗原,应用免疫印迹法,对95份经ⅡF检测为自身抗体阳性的癌患者血清进行分析,结果：癌组与对照组在阳性率,荧光图形、靶抗原细胞内定位上均有显著差别,两组人群的自身抗体阳性率皆随年龄增长而增高（P＜0．05）,而不同年龄段的癌患者组皆显著高于对照组（P＜0．01）;不同癌种间,上述结果差异皆无显著性（P＞0．05）,95份ⅡF阳性血清中,90份出现1条或多条阳性条带,其中多发性肌炎硬皮病自身抗体（抗PM－SCL）2份、抗Ku7份、抗着丝点蛋白抗体（抗CENP5份）、线粒体抗体2型（抗M2）9份、核糖蛋白抗（抗RNP)4份、干燥综合征Ａ抗原抗体（抗ＳＳ－Ａ）７份、组氨酰－tRNA合成酶抗体（抗Jo-1）1份、抗SS－A／SS－B5份、核糖体P蛋白抗体（抗Rib-P-Protein)4份,而另有多数条带对应靶抗原未明,结论,提示癌患者体内自身抗体具年龄相关性和癌种相关性。其自身抗体谱不同于正常人生理性自身抗类谱及自身免疫性疾病患者体内自身抗体谱,进一步研究自身抗体与癌的相关性,明确未知靶抗原本质,有助于深入认识癌患者的自身免疫理象。     

Solitary subcutaneous meningioma appearing as an osteolytic skull defect

Intraosseous meningiomas rarely present with osteolytic skull lesions. This case shows that meningioma must be added to the differential diagnosis of an osteolytic skull lesion.     

Ovarian teratomas appearing as solid masses on ultrasonography.

The purposes of this study were to evaluate the prevalence and imaging characteristics of ovarian teratomas that appear as solid masses on ultrasonography and to compare the ultrasonographic imaging features of the tumors with their pathologic findings. The ultrasonographic images of 202 ovarian teratomas were reviewed retrospectively. Solid-appearing masses were selected from among them and were evaluated in terms of internal echotexture, the presence or lack of peripheral hypoechogenicity, posterior sonic attenuation, and tumoral calcification. Seventy-six (37.6%) masses of 202 belonged to the atypical solid-appearing masses on ultrasonography. Of 76 masses, 57 (75.0%) had peripheral hypoechogenicity; 38 masses had well-defined thin hypoechoic rims, whereas 19 had poorly demarcated peripheral hypoechogenicity. Posterior sonic attenuation was evident in 18 (23.7%) masses. The presence of peripheral hypoechogenicity, which is suggestive of the fluid portion of the tumor, might be one of the characteristic findings of solid-appearing ovarian teratomas on ultrasonography.