The glycoprotein CD47 (integrin-associated protein, IAP) is present on the surface of virtually all cells, including red blood cells (RBCs). CD47 acts like a marker of self by ligating the macrophage inhibitory receptor signal regulatory protein alpha (SIRPalpha). In this manner mild reactivity of wild-type RBCs with macrophage phagocytic receptors is tolerated, whereas otherwise identical CD47-deficient RBCs are rapidly eliminated. We show here that virtually all CD47-deficient nonobese diabetic (NOD) mice spontaneously develop severe lethal autoimmune hemolytic anemia (AIHA) at 180 to 280 days of age, whereas none of the control CD47(+) NOD mice develop lethal AIHA at least during the first year of life. This phenotype is at least partially due to a markedly increased rate of elimination of opsonized CD47(-/-) compared to CD47(+) RBCs. Similarly, CD47(-/-)C57BL/6 mice were much more sensitive than their wild-type counterparts to experimental passive AIHA induced by anti-RBC monoclonal antibodies. Thus, CD47-SIRPalpha signaling can have a profound influence on the severity of AIHA, making manipulation of this signaling pathway a theoretically appealing avenue in the treatment of the disease. (+info)
Cell-mediated immunity in idiopathic autoimmune haemolytic disease.
(42/384)
Membrane antigens from autologous and from allogeneic red blood cells (RBC) induced migration inhibition of splenic leucocytes and transformation of peripheral blood lymphocytes from a patient with idiopathic autoimmune haemolytic disease (AHD). No migration inhibition occurred following stimulation of splenic leucocytes obtained during splenectomy from a patient with beta-thalassaemia major. Lymphocyte transformation did not occur when normal lymphocytes were stimulated by similar RBC membrane preparations. These findings indicate that autosensitization in AHD may be a function of both humoral and cellular immune mechanisms. (+info)
Successful treatment of refractory autoimmune haemolytic anaemia in a post-unrelated bone marrow transplant paediatric patient with rituximab.
(43/384)
Here, we report a case of paediatric beta-thalassaemia major patient who underwent unrelated T cell-non- depleted bone marrow transplantation and developed a complication of autoimmune haemolytic anaemia (AIHA) refractory to corticosteroid and intravenous immunoglobulin therapy. After this child received two doses (375 mg/m2/dose) of rituximab (anti-CD20 monoclonal antibody), his AIHA was resolved. (+info)
Ceftriaxone induced immune hemolytic anemia: detection of drug-dependent antibody by ex-vivo antigen in urine.
(44/384)
There have been a few reported cases of immune hemolytic anemia induced by ceftriaxone. We encountered a patient with immune hemolytic anemia that seemed to be stimulated by a degradation product of ceftriaxone. The patient's direct antiglobulin test was positive only for C3d, and no ceftriaxone-dependent antibodies were detectable in the patient's serum. To demonstrate the presence of the ceftriaxone-induced antibodies, an ex-vivo antigen in urine was obtained from the patient. In addition, we prepared a 1 mg/mL suspension solution of ceftriaxone, and group AB serum as a complement source. Using several combinations of the above reactants, the indirect antiglobulin test was performed. Only the indirect antiglobulin test using the patient's serum with the ex-vivo urine antigen was found to be positive. Other combinations were not reactive. To our knowledge, this is the first reported case in Korea, in which the causative antibody appeared to be stimulated solely by a degradation product of ceftriaxone. (+info)
High-dose cyclophosphamide for refractory autoimmune hemolytic anemia.
(45/384)
High-dose cyclophosphamide, without stem cell rescue, has been used successfully to treat aplastic anemia and other autoimmune disorders. To determine the safety and efficacy of high-dose cyclophosphamide among patients with severe refractory autoimmune hemolytic anemia, we treated 9 patients with cyclophosphamide (50 mg. kg(-1). d(-1) for 4 days) who had failed a median of 3 (range, 1-7) other treatments. The median hemoglobin before treatment was 6.7 g/dL (range, 5-10 g/dL). The median time to reach an absolute neutrophil count of 500/microL or greater was 16 days (range, 12-18 days). Six patients achieved complete remission (normal untransfused hemoglobin for age and sex), and none have relapsed after a median follow-up of 15 months (range, 4-29 months). Three patients achieved and continue in partial remission (hemoglobin at least 10 g/dL without transfusion support). High-dose cyclophosphamide was well tolerated and induced durable remissions in patients with severe refractory autoimmune hemolytic anemia. (+info)
T-cell specificity in murine autoimmune haemolytic anaemia induced by rat red blood cells.
(46/384)
Autoimmune haemolytic anaemia (AIHA) can be induced in mice by repeated injections with rat red blood cells (RBC). Here we describe the identification of rat and murine RBC antigens recognized by T-cells from mice with this disease. Splenic T-cells from mice with AIHA proliferated in response to multiple murine RBC membrane components, each of which is recognized by rat RBC induced autoantibodies. Thus, there were responses to murine autoantigen fractions that correspond in apparent molecular mass with the anion channel Band 3, with spectrin from the membrane skeleton and with the high and low molecular mass glycophorins, and the equivalent fractions from rat RBC also stimulated proliferation by T-cells. It was confirmed that purified Band 3 from murine and rat RBC also elicited responses. In contrast with the results in AIHA, T-cells from healthy control mice failed to respond to the antigens from either species, with the exception of proliferation induced by murine spectrin in one experiment and weak responses elicited by rat Band 3. It is suggested that T-cells activated by multiple cross-reactions between rat and murine RBC proteins, and by epitope spreading, are necessary to drive autoantibody production in this model of AIHA. (+info)
Rituximab-based chemotherapy for steroid-refractory autoimmune hemolytic anemia of chronic lymphocytic leukemia.
(47/384)
Autoimmune hemolytic anemia (AIHA) is a well known complication of chronic lymphocytic leukemia (CLL). Steroids are the first line of treatment and there are limited effective treatment options for steroid refractory AIHA of CLL. Rituximab, an active agent against B cell malignancies, has also been noted to be active in certain autoimmune hematologic disorders. We used a combination of rituximab, cyclophosphamide and dexamethasone (RCD) in eight CLL patients with steroid refractory AIHA. Rituximab was given at a dose of 375 mg/m(2) i.v. on day 1 (D-1). Cyclophosphamide was given at a dose of 750 mg/m(2) on D-2. Twelve mg of dexamethasone was given i.v. on D-1, D-2 and orally from D-3 to D-7. Cycles were repeated every 4 weeks till the best response. Response in AIHA was evaluated by frequent blood counts and Coombs test. All eight patients achieved a remission of their AIHA. Median pretreatment hemoglobin was 8.3 g/dl and post-treatment hemoglobin was 14.3 g/dl. Five patients converted to Coombs negative after RCD. Median duration of response was 13 months (7-23+). Retreatment with RCD was also effective in achieving a response on relapse of AIHA. Our results indicate that a rituximab-based combination regimen (RCD) is highly effective in treating steroid refractory AIHA of CLL. (+info)
Autoimmune hemolytic anemia predominantly associated with IgA anti-E and anti-c.
(48/384)
A patient with warm autoimmune hemolytic anemia (AIHA) due to predominance of immunoglobulin A (IgA) with an Rh specificity, considered to be the first case in Korea, is described. A 13-year-old male patient with severe hemolytic anemia showed a weak reactivity (1+) in the direct antiglobulin test (DAT) by using anti-IgG antiglobulin reagent. This finding, however, could not fully explain the patient's severe AIHA. When anti-IgA reagent was used for the DAT, strong reactivity (4+) was observed and free anti-E and anti-c autoantibodies were also detected by anti-IgA and anti-IgG reagents. The patient's hemoglobin began to rise with the administration of steroids. Because RBCs coated with multiple types of immunoglobulins are associated with more severe hemolysis than those only with IgG, the DATs using anti-IgA and other reagents are needed for the correct diagnosis when the result of DAT is not compatible with patient's clinical manifestations. (+info)