1/12. Paroxysmal cold haemoglobinuria in an adult with chicken pox.Paroxysmal cold haemoglobinuria (PCH) is an autoimmune disorder characterized by intravascular haemolysis causing haemoglobinuria. It is due to a biphasic haemolysin known as the Donath-Landsteiner antibody, which binds specifically to the P antigen of red blood cells at low temperatures, leading to complement activation and red cell lysis at 37 degrees C. PCH is a rare disease which predominantly affects the paediatric population, occurring mostly during viral infections. We report on what is possibly the first case of PCH in an adult to be precipitated by chicken pox infection.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/12. Acute myelogenous leukemia with PIG-A gene mutation evolved from aplastic anemia-paroxysmal nocturnal hemoglobinuria syndrome.We report a patient with aplastic anemia (AA)-paroxysmal nocturnal hemoglobinuria (PNH) syndrome who developed acute myelogenous leukemia (AML). Flow cytometric analysis showed that the leukemic cells in the bone marrow lacked CD59 antigen on their surface and were positive for p-glycoprotein. Heteroduplex and single-strand conformation polymorphism analysis followed by sequencing of the leukemic cells in the bone marrow disclosed 1 frameshift-type mutation in exon 2 of the phosphatidylinositol glycan-class A (PIG-A) gene, which deductively produces truncated PIG-A protein. These findings provide direct evidence that the leukemic cells evolved from the affected PNH clone. cytogenetic analysis in the bone marrow in each stage of AA-PNH, AML, and at relapse of AML showed normal, -7, and -7 plus -20, respectively, showing evidence of a clonal evolution. Because complete remission of AML was not achieved by intensive chemotherapies, allogeneic peripheral blood stem cell transplantation (PBSCT) from the patient's HLA-matched sister was performed successfully with recovery of CD59 antigen on bone marrow hematopoietic cells; however, leukemia relapsed 4 months after PBSCT. leukemia derived from PNH may be resistant to intensive chemotherapy, and a highly myeloablative regimen may be required for stem cell transplantation to eradicate the PNH-derived leukemia clone.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
3/12. Successful application of nonmyeloablative transplantation for paroxysmal nocturnal hemoglobinuria.OBJECTIVE: Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired clonal hematopoietic stem cell disorder that manifests as hemolytic anemia, venous thrombosis, and deficient hematopoiesis. Although allogeneic hematopoietic stem cell transplantation is considered the only curative therapeutic measure, transplant-related mortality is not negligible. Several studies supported the use of nonmyeloablative stem cell transplantation (NST) for patients of advanced age or with organ dysfunction. Hence, we used NST in a PNH patient who suffered from acute renal failure due to repeated episodes of hemolysis. MATERIALS AND methods: We performed NST using a conditioning regimen consisting of cladribine 0.11 mg/kg x 6, busulfan 4 mg/kg x 2, and rabbit anti-thymocyte globulin 2.5 mg/kg x 2. He received peripheral blood stem cells from his human leukocyte antigen-matched brother. Prophylaxis against graft-vs-host disease was performed with cyclosporine A alone. chimerism of peripheral blood mononuclear cells was evaluated serially using short tandem repeat analysis and flow cytometry. RESULTS: No meaningful regimen-related toxicities were documented. Donor chimerism of 90 to 100% was achieved on day 14 and thereafter. The patient is doing well, without any recurrence of hemolysis 6 months after transplant. Follow-up chimerism studies confirmed stable and functioning donor-type hematopoiesis. CONCLUSIONS: NST may become a safe and curative approach in patients with PNH. Further studies are needed to establish the role of NST for treatment of PNH.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
4/12. association of clonal T-cell large granular lymphocyte disease and paroxysmal nocturnal haemoglobinuria (PNH): further evidence for a pathogenetic link between T cells, aplastic anaemia and PNH.There is mounting evidence to suggest that T-cell-mediated suppression of haemopoiesis is a pathogenetic mechanism in three bone marrow failure syndromes: aplastic anaemia (AA), paroxysmal nocturnal haemoglobinuria (PNH) and myelodysplasia (MDS). T-cell microclones can be detected by sensitive polymerase chain reaction (PCR)-based methods in all three disorders. Recently, larger clonal populations of T-cell large granular lymphocytes (T-LGLs) have been observed in some patients with AA and MDS. Here, we report the development of a large clonal T-LGL population in a patient with bona fide PNH. In this patient, we defined part of the sequence of the T-cell receptor (TCR) beta-chain gene, and we have shown that the large T-LGL population emerged from a background of multiple smaller T-cell clones. Thus, T-LGL clones in AA, MDS and PNH probably expand as a result of antigenic stimulation. It is postulated that the antigen driving clonal T-cell proliferations in these disorders exists on haemopoietic stem cells.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
5/12. Acquired and transient RBC CD55 deficiency (Inab phenotype) and anti-IFC.BACKGROUND: antigens of the Cromer blood group system reside on the glycoprotein CD55 (decay-accelerating factor). The Inab phenotype is the null phenotype of this system. So far, only five propositi have been described who exhibit this phenotype, and single-nucleotide substitutions in the CD55 gene have been found in three of them. This report describes the first example of a patient with an acquired and transient form of the Inab phenotype. CASE REPORT: A 54-year-old black patient was admitted to the hospital because of abdominal pain. Multiple splenic infarctions were visualized in the abdominal computerized tomography scan, and a prophylactic splenectomy was performed. The patient's serum reacted by an IAT with all donor RBCs tested. RESULTS: Serologic analysis showed that the patient had the rare Inab phenotype and that his serum contained anti-IFC. flow cytometry demonstrated the absence of CD55 on his RBCs, whereas lymphocytes, monocytes, granulocytes, and platelets expressed CD55, albeit at a weaker level than cells of common phenotypes. cDNA revealed no differences from the published sequences. flow cytometry performed 12 months after splenectomy showed reappearance of the CD55 antigen; serologic tests performed after 17 months revealed that the anti-IFC had almost disappeared and that the RBCs were again agglutinated by various Cromer antibodies. CONCLUSION: A patient with an acquired and transient form of the Inab phenotype is described, in whom the CD55 deficiency is limited to the RBCs and is associated with splenic infarctions.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
6/12. Expression of phosphatidylinositol anchored membrane proteins in paroxysmal nocturnal haemoglobinuria after bone marrow transplantation.A 20-year-old male with severe bone marrow failure associated with paroxysmal nocturnal haemoglobinuria (PNH) underwent an allogeneic bone marrow transplantation (BMT). Flow cytometric analysis of phosphatidylinositol (PI) anchored membrane proteins prior to BMT showed a markedly reduced expression of monocyte CD14 and neutrophil CD16 molecules. On day 17 after BMT expression of both antigens reached normal values and remained stable throughout a follow-up period of 10 months, thus confirming the eradication of the PNH clone. To date, this is the first case in which normal expression of PI-anchored proteins after BMT is reported.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
7/12. pyoderma gangrenosum: clinical and laboratory findings in 15 patients with special reference to polyarthritis.Fifteen consecutive patients with PG have been studied during the period 1971-78. Systemic disease was found in 13 of the patients and preceded the skin disease in 10 patients by 1-25 years. Only two patients had ulcerative colitis. One patient had paroxysmal nocturnal hemoglobinuria and three patients had an IgA myeloma. Eight patients had polyarthritis; this was classical seropositive rheumatoid arthritis in two patients, and a seronegative inflammatory polyarthritis in six patients. Four patients had an unusual progressive erosive seronegative polyarthritis without evidence of granulomatous bowel disease, psoriasis, genital, urinary tract or eye disease. In three of these four patients the arthritis preceded the PG. synovial fluid analysis showed depressed complement levels and in one patient deposits of immunoglobulins and complement were demonstrated in the synovial membrane. The course of the arthritis was progressive with development of disabling joint deformities and erosive destruction of joints, despite treatment with penicillamine, corticosteroids and nonsteroidal anti-inflammatory drugs. One other patient had severe degenerative joint disease and chondrocalcinosis in association with a seronegative inflammatory polyarthritis, and another patient had ulcerative proctitis and severe degenerative joint disease secondary to chronic seronegative inflammatory polyarthritis. None of the patients had colitic arthritis, but in view of the association between PG and ulcerative colitis, some patients previously reported with PG and joint disease may have been suffering from the arthritis of ulcerative colitis. PG developed at the site of skin trauma in six patients. The natural history of the skin disease ran one of two courses: an acute, progressive course in which the ulcers rapidly enlarged until arrested by treatment; and a chronic course in which the lesions extended slowly and which after a period of weeks began to show signs of spontaneous healing. In only the patients with ulcerative colitis was there any correlation between the activity of the associated disease and the onset and progression of the skin disease. serum complement levels were normal and no circulating cryoprecipitable immune complexes were found. skin histology showed no evidence of vasculitis and direct immunofluorescence examination of involved skin was negative for IgG, IgM, IgA and C3. No consistent abnormality of cell-mediated immunity or neutrophil function was found and no significantly increased prevalence of any HLA antigen type was noted. Twelve patients have been treated with systemic corticosteroids. Six of these patients developed serious steroid complications and four patients have died, all from complications of steroid therapy.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
8/12. Expression of cryptantigen Th on paroxysmal nocturnal hemoglobinuria erythrocytes in association with a hemolytic exacerbation.Paroxysmal nocturnal hemoglobinuria (PNH) erythrocytes lack complement regulatory membrane proteins and are susceptible to complement. Although the critical role of complement in intravascular hemolysis in PNH is accepted, the precise mechanism of complement activation in vivo is unknown. Accordingly, in a PNH patient who was suffering from a hemolytic precipitation soon after a common cold-like upper respiratory infection, we analyzed the erythrocytes with lectins and by flow cytometry to detect membrane alteration that lead to complement activation. The lectin reactivity of erythrocytes showed the expression of cryptantigen Th. The patient serum at the time of the hemolysis induced the expression of Th on erythrocytes from PNH patients and from healthy volunteers in vitro, whereas neither the patient serum after recovery from the hemolysis nor blood type-matched control serum from healthy donor showed this activity. Moreover, autologous serum selectively hemolyzed Th PNH erythrocytes, but not Th- PNH erythrocytes, or Th control erythrocytes. hemolysis was not observed either in complement-inactivated serum or in blood type-matched cord blood serum, which lacks natural antibodies to cryptantigens. These findings indicate that the immunoreaction of infection-induced Th with natural antibody on PNH erythrocytes is a trigger of the complement activation, leading to intravascular hemolysis.- - - - - - - - - - ranking = 6keywords = antigen (Clic here for more details about this article) |
9/12. Discordant and heterogeneous expression of GPI-anchored membrane proteins on leukemic cells in a patient with paroxysmal nocturnal hemoglobinuria.We performed a flow cytometric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (CD59/MACIF) in order to investigate the leukemic cells and erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed acute myelocytic leukemia. In May 1990, the leukemic cells comprised 70% of the mononuclear cells in the bone marrow and 76% of those in the peripheral blood. They consisted of a mixture of positive and negative populations, including single DAF-positive cells. In August 1990, almost 100% of the peripheral mononuclear cells were leukemic blasts, and these consisted of a single population with reduced DAF expression. Single-color flow cytometric analysis showed that the leukemic cells lacked CD59/MACIF, while control leukemic cells (n = 3) expressed both DAF and CD59/MACIF. Leukemic blasts from this patient and six control patients expressed lymphocyte function-associated antigen 3 and FcIII receptors (CD 16) both before and after treatment with phosphatidylinositol-specific phospholipase C. The patient's erythrocytes lacking DAF and CD59/MACIF expression corresponded to the proportion of complement-sensitive cells at the onset of acute leukemia. These DAF- and CD59/MACIF-deficient erythrocytes disappeared almost completely with progression of the leukemia. In conclusion, it appears that the expression of glycosylphosphatidylinositol-linked membrane proteins by leukemic cells was heterogeneous and discordant in our patient, and that the leukemic cells were derived from the PNH clone because of their deficiency of CD59/MACIF. It is also suggested that DAF could compete more effectively than CD59/MACIF for a limited number of anchor molecules available on the proliferating leukemic cells.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
10/12. Report on a patient with paroxysmal cold hemoglobinuria.antibodies against the human blood group P antigen (anti-P alloantibodies) agglutinate phenotype P1 and P2 erythrocytes treated with papain at 4 degrees C but not phenotype PK and p erythrocytes. This condition is referred to as an autoimmune disease of paroxysmal cold hemoglobinuria (PCH), and the anti-P specificity is found in the cold hemagglutinins. serum from a patient suspected to be suffering from PCH by the cold auto-agglutination properties was tested for anti-P specificity, using papain-treated O blood group erythrocytes. The serum-mediated hemagglutination and the serum and complement-mediated immunohemolysis were inhibited by globoside (P antigen GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc-ceramide) and Forssman glycosphingolipid (GalNAc alpha 1-3GalNAc beta 1-3Gal alpha 1-4Gal beta 1-4Glc-ceramide). Therefore, we concluded that she had PCH. She was completely cured 6 months later.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
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