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[Immunological studies of thrombotic thrombocytopenic purpura].

We studied the immunological changes in eight cases of thrombotic thrombocytopenic purpura (TTP). At autopsy, one case showed IgM deposition in the walls of the capillaries of heart and spleen. Coombs' test was negative in all cases and rheumatic factor was positive in four of eight cases. Anti-nuclear factor was positive in three cases including one case showed positive only during remission. One case, who was diagnosed as TTP complicated with systemic lupus erythematosus (SLE) showed some serological abnormalities for LE test, anti-streptkinase, anti-DNA antibodies, platelet bound IgG, and serum level of IgG by renal biopsy. There were little changes in complements levels. Platelet associated IgG (PAIgG) was positive in four of six cases, and this seemed to be the only abnormality associated with remission and relapses of TTP.

Adult↗

Specific anti-erythrocyte focus formation as a measure of autoantibody secreting cells in NZB mice.

Using a modification of the antibody forming cell (AFC) focus assay, it is possible to quantitate the spontaneous anti-erythrocyte autoantibody response of New Zealand Black (NZB) mice at the level of the autoantibody secreting cell. This complement independent assay is specific for an antigen(s) present on unmodified mouse erythrocytes. A comparison with the direct Coombs' test showed that the focus assay detected autoantibody responses earlier and demonstrated a wide range of AFC levels in responding mice. The focus assay provides a method for evaluating autoimmunity at the cellular level and for investigating the activities of cells responding to autoantigens.

Anemia, Hemolytic, Autoimmune↗

[On the differential diagnosis of hemolytic anemia (author's transl)].

Differential diagnosis of hemolytic anemia is discussed, with regard to the classification into corpuscular and extracorpuscular types of hemolysis. Presence of antibodies in a patient's serum, indicate extracorpuscular-acquired hemolytic anemia. Coombs test may be positive or negative according to the antibody present. A primary disease has to be excluded in each case. Abnormal hemoglobin, defect of the corpuscular-hereditary type. Direct laboratory enzyme estimation indicate enzyme deficiency (Glucose-6-P-dehydrogenase, Pyruvate-kinase, Glutathione-reductase). Hemoglobinelectrophoresis and special tests for unstable hemoglobins indicate this type of disturbance. For defect of the membrane measuring of osmotic fragility might be helpful. Activity of membrane enzymes and introduction of 32P in the fractionated membrane lipids, point out special types of a deficient membrane. 6 of our own cases are discussed.

Anemia, Hemolytic↗

Primary pure red cell aplasia in dogs: 13 cases (1996-2000).

OBJECTIVES: To examine clinical features, laboratory test results, treatment, and outcome of dogs with pure red cell aplasia (PRCA). DESIGN: Retrospective study. ANIMALS: 13 dogs with severe nonregenerative anemia and bone marrow erythroid aplasia. PROCEDURES: Medical records of dogs determined to have PRCA on the basis of results of blood and bone marrow analysis between 1996 and 2000 were reviewed. Criteria for inclusion in the study were severe nonregenerative anemia (Hct < 20%; reticulocyte count < 1.0%), selective erythroid aplasia in bone marrow, and lack of underlying diseases that may have caused the anemia. RESULTS: Median age of dogs was 6.5 years. Females were significantly overrepresented. Median Hct was 10%, and median reticulocyte count was 0.1%. Direct Coombs' test results were negative for all dogs tested, and spherocytosis was evident in 2 dogs. All dogs were treated with prednisolone, and 2 dogs were treated with prednisolone and cyclophosphamide. Responses to treatment were complete, partial, and poor in 10, 1, and 2 dogs, respectively. Median time required to achieve an increase of 5% or more in Hct was 38 days, and median time to complete remission was 118 days. Of 10 dogs for which follow-up information was available, only 1 required long-term immunosuppressive treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with PRCA appear to respond readily to treatment with immunosuppressive drugs; however, hematologic responses may not be observed for weeks to months after initiation of treatment.

Animals↗

Experimental erythrocyte autoimmunity. Specificity of autoantibodies of autoantibody-specific suppressor cells elicited by RBC from various strains of rats.

Autoantibodies and autoantibody-specific suppressor cells are produced in mice injected with RBC from rats. In this report it is shown, first, that the RBC from various strains of rats stimulate similar clones of auto-reactive B-cells. The evidence for this conclusion was obtained using antibodies eluted from the RBC and sera from mice positive in direct Coombs' tests. Autoantibodies elicited by RBC from any strain of rat were absorbed by RBC from all strains of rat tested but not by sheep RBC. Secondly, it is shown that spleen cells from mice injected with RBC of one strain of rat delayed autoantibody production elicited by RBC from syngeneic and allogeneic rats when transferred to syngeneic mice before the first injection of rat RBC. Serum antibody levels to rat RBC were not reduced.

Animals↗

Induction of persistent autoimmune haemolytic anaemia in mice by combined use of rat erythrocyte preimmunization and chronic GVHR.

Female F1 mice (BDF1: C57BL/6 x DBA/2, BCF1: C57BL/6 x C3H/HeN, BBF1: C57BL/6 x BALB/c) were preimmunized with rat erythrocytes and then received splenic T cells from parental female C57BL/6 mice injected with hydrocortisone acetate before killing. In BDF1 and BCF1 mice, direct Coombs' test (DCT) positivity persisted for more than 4 months in almost all mice. They also showed haematological sign of anaemia, and the survival of infused 51Cr-labelled parental C57BL/6 erythrocytes was reduced. In BBF1 mice, DCT positivity returned to negative within 2 months. Autoantibodies were eluted from DCT-positive erythrocytes and their specificities were examined. They were capable of binding equally well to erythrocytes from all strains of mice tested, including the donor mice. They also cross-reacted with rat erythrocytes but not with sheep, rabbit or human erythrocytes. Isotypes of the autoantibodies eluted were also examined. Interestingly, isotypes of the autoantibodies obtained from individual mice were confined to one or other subclass of IgG isotype: IgG1, IgG2a or IgG2b.

Anemia, Hemolytic, Autoimmune↗

Immune thrombocytopenia attributed to brucellosis and other mechanisms of Brucella-induced thrombocytopenia.

Thrombocytopenia often complicates the course of acute brucellosis, mainly due to bone marrow suppression or hypersplenism. Immune thrombocytopenia is also reported in brucellosis, resulting usually in massive thrombocytopenia, purpura, and spontaneous hemorrhage. We describe a case of acute brucellosis in an 85-year old woman, who presented with fever, purpuric skin lesions, anemia, and rhinorrhagia. The absolute platelet count was 1000/microL. Direct and indirect Coombs tests were positive, and a cold-agglutinin was detected. The patient was diagnosed as suffering from brucellosis on the basis of a strongly positive serologic reaction and was treated with doxycycline, streptomycin, and a short course of corticosteroids, with a rapid rise in platelet number.

Acute Disease↗

Immune-mediated haemolytic anaemia in two sibling cats associated with multicentric lymphoblastic infiltration.

Immune-mediated haemolytic anaemia associated with multicentric lymphoblastic infiltration is reported in two sibling cats. Both cats presented at under 16 months of age with clinical signs of acute anaemia. In each case there was autoagglutination, a positive Coombs' test and the anaemia was regenerative. At presentation, both cats were negative for FeLV antigen. In each case, the disease proved fatal within 2 months of the initial diagnosis. In both cases, T-lymphoblastic infiltration of bone marrow, liver and spleen was found at post-mortem examination.

Anemia, Hemolytic, Autoimmune↗

Management of severe neonatal anemia due to fetomaternal transfusion.

Three cases of severe neonatal anemia due to fetomaternal transfusion are reported. The key features that lead to early diagnosis were the maternal history, fetal monitoring, the clinical and laboratory findings of anemia, and a negative Coombs test. Diagnosis was confirmed by a rapid Kleihauer-Betke test. A partial exchange transfusion was performed in two of the three neonates with rapid clinical and hematological improvement. As two patients showed signs of heart decompensation, a partial exchange transfusion was performed with good success. In patients presenting with severe subacute or chronic anemia and heart failure, a partial exchange transfusion may be preferable to that of simple transfusion associated with diuretics.

Adult↗

Anti-erythrocyte antibodies in ulcerative colitis: case report and discussion on the pathophysiology of anti-erythrocyte antibody.

A case of ulcerative colitis (UC) associated with anti-erythrocyte antibodies is reported. A 27-year-old male visited our department because of a relapse of UC, and his condition was diagnosed as severe and extensive colitis. He was vigorously treated with prednisolone (50 mg/day i.v.) and TPN, but no response was obtained. Subtotal colectomy with ileostomy was performed on the 22nd hospital day, and a proctosigmoidectomy was performed on him six months later. Preoperative blood type and screen disclosed that his blood was not cross-matched either on the forward or reverse typing. His ABO blood group could not be identified as "B", as determined upon admission, and his Coombs' test was positive. Further studies revealed that his Rh group was CcDEe. Anti-I antibody was detected in his serum and eluate from erythrocytes were identified as anti-E and c. Titers of the antibodies were strongest in the preoperative period and became weak following colectomy, but the antibodies did not disappear even after the large bowel was totally removed.

Adult↗

Induction of direct Coombs positivity with alpha-methyldopa in chimpanzees.

Two of four chimpanzees developed a moderately strong positive direct Coombs test after injection of stroma of their autologous erythrocytes that had been treated with alpha-methyldopa in the presence of diethyldithiocarbamate. Similar experiments with rabbits were unsuccessful. The results are concluded to be a demonstration that the first step in the development of autoantibody in alpha-methyldopa therapy is interaction of the oxidized drug with certain, as yet unidentified, peptides of the erythrocyte membrane.

Anemia, Hemolytic, Autoimmune↗

Expression and regulation of erythrocyte auto-antibodies in mice following immunization with rat erythrocytes.

Mice immunized with intact rat red blood cells (RBC) developed serum auto-antibodies (some of which were mouse specific) to the RBC membrane components spectrin and antigens of 100 and 81 kDa as shown by Western blotting and enzyme-linked immunosorbent assay as well as RBC surface-bound autoantibodies detected by the Coombs' test. In order to discover whether these autoantibodies were induced and controlled in similar or different ways, mice were challenged with a variety of rat and mouse RBC preparations. In addition, the ability of recipients given spleen cells from the above donors to generate autoantibody responses to intact rat RBC was measured. It was found that all the autoantibodies were induced in mice challenged with rat RBC ghosts but none following immunization with butanol-extracted rat RBC ghosts or intact mouse RBC. By contrast, mice injected with mouse RBC ghosts made autoantibodies to spectrin and to the 100-kDa band. Spleen cells from mice primed with intact rat RBC, rat RBC ghosts or butanol-extracted rat RBC ghosts curtailed Coombs' autoantibody production of recipient mice challenged with intact rat RBC. Serum from recipients of spleen cells primed with intact rat RBC or the butanol extract generally failed to react with rat or mouse spectrin or with the 81-kDa band, although antibody was detected to the rat 100-kDa band. Recipients of rat RBC ghost-primed spleen cells produced antibody to rat and mouse spectrin and to rat 100-kDa band but not to mouse 100-kDa or rat or mouse 81-kDa bands. Occasionally, suppression of antibody to the rat-specific 38-kDa band was observed in recipients of intact rat RBC-primed spleen cells. It is therefore suggested that regulation of cross-reactive and mouse-specific autoantibodies as well as rat-specific antibodies occurs in an independent, determinant-specific manner.

Animals↗

[Haemodialysis for renal failure in a case of systemic lupus erythematosus (author's transl)].

Severe acute renal failure developed in a patient with systemic lupus erythematosus which was characterized by typical skin rash, polyserositis, haemolytic anaemia and liver damage. Serological examination revealed anti-DNA antibodies in high concentrations, positive Coombs' test, excessive elevation of serum-IgG with markedly depressed serum complement fractions (C3, C4). Acute lupus nephritis led to prolonged oliguria and anuria requiring regular dialysis over almost five months. Immuno-suppressive treatment with cortisone and azathioprine finally reversed the renal failure: BUN returned to 33 mg/ 100 ml, with a plasma creatinine of 1.8 mg per 100 ml.

Acute Kidney Injury↗

[Mixed-type autoimmune hemolytic anemia after splenectomy for idiopathic thrombocytopenic purpura].

A 30-year-old woman was admitted because of anemia and jaundice in 1999. She had been diagnosed as having idiopathic thrombocytopenic purpura (ITP) in 1996, but had shown no response to prednisolone (PSL). Subsequent splenectomy in 1998, followed by further treatment with PSL, had also been ineffective. On admission in 1999, the direct and indirect Coombs tests gave positive results, the cold agglutinin titer was high with anti-I specificity (IgM), and warm-type autoantibody (IgG) was positive. Autoagglutination of the patient's red blood cells was 3+ at 37 degrees C. A diagnosis of mixed-type autoimmune hemolytic anemia (AIHA) associated with ITP was made. Mixed-type AIHA occurring after splenectomy for ITP is very rare, only one case having been reported to date.

Adult↗

[Specific antibodies bound to secretory IgA in the sera of patients with intestinal infections].

Specific IgA and sIgA antibodies were studied in the sera of patients suffering from various intestinal diseases (dysentery, salmonellosis, typhoid fever, chronic typhoid carrier state) and in the sera of healthy persons immunized by parenteral route with typhoid alcohol vaccine. The nature of antibodies was identified in Coombs' test, using monospecific antisera to alpha-chain and to the secretory component. IgA and sIgA antibodies were revealed most frequently in the sera of dysentery patients and of chronic typhoid carriers. No sIgA antibodies were found in the sera of subcutaneously immunized persons. The presence of specific sIgA antibodies in the serum reflects the participation of local immune mechanisms in the formation of systemic immunity in the intestinal infections.

Chronic Disease↗

The acute and transient nature of idiopathic immune hemolytic anemia in childhood.

The records of 22 children with the diagnosis of idiopathic immune hemolytic anemia were reviewed. Fifty per cent of the children had a history of an antecedent infection and 32% had underlying immune deficiency or lymphoproliferative diseases. The majority (77%) of the patients had an acute self-limited disease which was frequently associated with a positive complement or nongamma Coombs test. The anemia was usually severe, and a number of the children had reticulocytopenia at the time of diagnosis. These children responded rapidly to transfusions and corticosteroids and generally remained well on follow-up. Immunosuppressive drugs did not prove useful in two patients refractory to prednisone, but splenectomy was apparently beneficial in three of four patients so treated. Mortality rate was 18%, with most of the deaths related to an underlying disease.

Acute Disease↗

Monocyte ingestion of IgG-coated erythrocytes from haemolysing and non-haemolysing subjects.

A number of individuals in the population, including healthy blood donors and patients on methyldopa, show evidence erythrocyte coating by IgG autoantibodies (postive direct Coombs' test) without signs of a haemolytic state. The readiness with which red cells from these subjects are taken up by normal human monocytes in short term culture was examined, and compared with the phagocytosis of red cells from cases of IgG-mediated haemolytic anaemia. Red cells from non-haemolysing subjects were as avidly ingested in this system as were red cells from haemolysing patients. Similar results were obtained using normal red cells sensitised with antoantibody eluted from the cells of a healthy blood donor.

Anemia, Hemolytic, Autoimmune↗