1/275. Autologous bone marrow transplantation for recurrent malignant lymphoma after liver transplantation.BACKGROUND: Cancer chemotherapy in chronic carriers of hepatitis b virus is known to promote viral replication, and, when immunosuppressive treatment is stopped, the return of immune competence can be followed by a fulminant hepatitis. liver transplantation may be required and has been successfully performed for this condition. However, malignancy recurrence after transplantation has not been reported yet. methods AND RESULTS: We here report the case of an asymptomatic hepatitis B surface antigen carrier who developed a malignant lymphoma, which was treated by chemotherapy. After cessation of chemotherapy, he developed a fulminant hepatitis, requiring liver transplantation. Three years later, he developed a recurrent malignant lymphoma, which was treated successfully by autologous bone marrow transplantation. In order to prevent viral replication, lamivudine and intermittent administration of fresh-frozen plasma highly concentrated in anti-HBs immunoglobulin was initiated before the bone marrow transplantation. The patient remains well 12 and 56 months after autologous bone marrow and liver transplantation, respectively. CONCLUSIONS: This experience suggests that all hepatitis B surface antigen-positive patients for whom chemotherapy is indicated would benefit from prophylactic antiviral hepatitis b virus therapy. Furthermore, successful autologous bone marrow transplantation is possible after liver transplantation.- - - - - - - - - - ranking = 1keywords = antigen (Clic here for more details about this article) |
2/275. Recurrent macular corneal dystrophy type II 49 years after penetrating keratoplasty.recurrence of macular corneal dystrophy after keratoplasty is rare. We report light microscopic, immunohistochemical, electron microscopic, and serologic findings in a 78-year-old woman who underwent regrafting 49 years following the first penetrating keratoplasty. Examination of the corneal button revealed deposits of glycosaminoglycans in the graft beneath the Bowman layer, throughout the stroma, and in the endothelium with positive staining for antigenic keratan sulfate. By transmission electron microscopy, intracellular and extracellular deposits of a fibrillogranular material were detected in the stroma, descemet membrane, and endothelium. The serum level of antigenic keratan sulfate was normal. Our findings indicate that macular corneal dystrophy type II may show late recurrence after penetrating keratoplasty with intense deposition of antigenic keratan sulfate in all corneal layers.- - - - - - - - - - ranking = 1.5keywords = antigen (Clic here for more details about this article) |
3/275. Successful one antigen mismatched bone marrow transplant for chronic myeloid leukemia (CML) after two failed syngeneic transplants.In May 1989, a 43-year-old woman with chronic myelocytic leukemia diagnosed in 1988 underwent a syngeneic bone marrow transplant (BMT), conditioned with cyclophosphamide-TBI while in chronic phase. Three years later, because of both cytogenetic and hematological relapse, she was treated with interferon-alpha (IFN-alpha) and hydroxyurea (HU) for 3 years. In 1994 while still in chronic phase, she was conditioned with busulfan-cyclophosphamide (BU-CY) and underwent a second syngeneic BMT. In 1996, following a further cytogenetic and hematological relapse, she was again placed on IFN-alpha and HU therapy for 13 months, when she was referred to our hospital in accelerated phase. In October 1997 following thiotepa, CY and anti-thymocyte globulin conditioning, she underwent an allogeneic BMT from her 1-Ag mismatched brother. She became Ph1 negative with full chimerism and normal hematological parameters; acute graft-versus-host disease (GVHD) grade 3 of the skin and chronic GVHD of the liver occurred. At 11 months follow-up she is in good clinical condition and with a Karnofsky score of 90%. The role of a graft-versus-leukemia (GVL) effect in securing and maintaining the complete remission is discussed.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
4/275. Selection of hepatitis B surface "escape" mutants during passive immune prophylaxis following liver transplantation: potential impact of genetic changes on polymerase protein function.CASE REPORT: A patient is described who developed hepatitis b virus (HBV) reinfection five months following liver transplantation. Failure of hepatitis B immunoglobulin prophylaxis was associated with the emergence of mutations. HBV gene sequencing identified nucleotide substitutions associated with amino acid changes, one within the major hydrophilic region (MHR) of the HBV surface antigen at amino acid position 144 and one outside the MHR. Because of the overlapping reading frames of surface and polymerase genes, the latter surface antigen change was associated with an amino acid change in the polymerase protein. The patient developed significant allograft hepatitis and was treated with lamivudine (3TC) 100 mg daily. Rapid decline of serum HBV dna was observed with loss of HBV e antigen and HBV surface antigen from serum. There was normalisation of liver biochemistry, and liver immunohistochemistry showed a reduction in HBV core and disappearance of HBs antigen staining. CONCLUSION: Surface antigen encoding gene mutations associated with HBIg escape may be associated with alteration of the polymerase protein. The polymerase changes may affect sensitivity to antiviral treatment. Selection pressure on one HBV reading frame (for example, HBIg pressure on HBsAg, or nucleoside analogue pressure on polymerase protein) may alter the gene product of the overlapping frame. Such interactions are relevant to strategies employing passive immune prophylaxis and antiviral treatment.- - - - - - - - - - ranking = 3keywords = antigen (Clic here for more details about this article) |
5/275. association of lamivudine resistance in recurrent hepatitis B after liver transplantation with advanced hepatic fibrosis.BACKGROUND: Orthotopic liver transplantation (OLT) in patients with hepatitis b virus (HBV) infection is known to be associated with a high recurrence rate and poor prognosis. lamivudine, a nucleoside analogue, is a potent inhibitor of HBV replication, but it is associated with a 14-39% rate of resistance. methods: We report on four patients who underwent OLT for HBV infection. In all cases, the HBV infection recurred in the grafted liver and was treated with lamivudine (100 mg daily) on a compassionate-use basis. The patients were monitored closely for serum liver enzymes, hepatitis B surface antigen and HBV dna (by hybridization). Liver biopsy was performed before and after lamivudine therapy. HBV dna was amplified from serum for each patient and sequenced through a conserved polymerase domain, the tyrosine-methionine-aspartate-aspartate (YMDD) locus. RESULTS: All four patients exhibited lamivudine resistance 9-20 months after initiation of the drug. In all patients with a clinically mild disease, liver histology findings (12-24 months after lamivudine therapy) showed progressive fibrosis as compared to biopsies performed before lamivudine therapy, with a significant increase (> or =2 points) in the Knodell score in three patients. Moreover, two patients exhibited worsening of the necroinflammatory process. A mutation at the YMDD motif of the HBV polymerase gene was detected in all cases. CONCLUSIONS: lamivudine resistance frequently occurs in patients with recurrent HBV infection after OLT and is associated with advanced hepatic fibrosis and necroinflammatory process. A combination of antiviral therapies may be necessary.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
6/275. Recurrent miller fisher syndrome: clinical and laboratory features and hla antigens.In rare cases, miller fisher syndrome (MFS) has been known to recur. However, clinical features of recurrent MFS have not been well analyzed, and the precipitating factors relating to recurrence remain unknown. From 1981 to 1996, we examined four patients with recurrent MFS among 28 Japanese MFS patients. In the four patients, the recurrent episodes occurred after long asymptomatic intervals, ranging from 2.5 to 12.5 years. The clinical and laboratory features of recurrent episodes were similar either to those of the initial episodes or to those of the 24 non-recurrent patients. Of the two patients tested for serum IgG anti-GQ1b antibody, both were positive. Serological HLA typing showed that all recurrent patients were both HLA-Cw3 and -DR2 positive. However, out of 13 non-recurrent patients examined, six had HLA-Cw3, and four had HLA-DR2. The frequency of HLA-DR2 among the recurrent patients was significantly higher than among healthy controls (corrected P = 0.038), and was also higher than among the non-recurrent patients but not significantly. These findings suggest that recurrent MFS is clinically the same as typical MFS and that HLA-DR2 is possibly associated with recurrence.- - - - - - - - - - ranking = 2keywords = antigen (Clic here for more details about this article) |
7/275. Antigenic characterization of pre- and post-liver transplant hepatitis B surface antigen sequences from patients treated with hepatitis B immune globulin.BACKGROUND/AIMS: The success of treatment with hepatitis B hyperimmune globulin in preventing recurrence of hepatitis b virus infection in patients undergoing orthotopic liver transplantation depends on maintaining levels of anti-HBs sufficient to neutralise hepatitis b virus and also on patient compliance. Breakthrough infections may occur, and these have been associated with the emergence of variants in HBsAg. methods: Three patients, two who relapsed and one who had no evidence of hepatitis b virus infection post-orthotopic liver transplantation were studied. polymerase chain reaction and sequencing of pre- and post-orthotopic liver transplantation samples was followed by antigenic analysis of the in vitro expressed cloned sequences. RESULTS: In two patients who were treated with hyperimmune globulin, amino acid variation in the region of the immunodominant B cell epitopes of HBsAg occurred. Sequencing of clones revealed fluctuating variant sequences over time. One had clinical relapse and immune escape was evident on in vitro antigenic analysis. Patient two lost HBsAg reactivity post-orthotopic liver transplantation. There was loss of an antigenically critical cysteine molecule; sequencing of clones revealed that this was the dominant species. The third patient relapsed when protective levels of anti-HBs were not maintained; HBsAg showed no variation compared to a standard subtype sequence. CONCLUSION: These data provide strong experimental evidence of immune escape. It appears that hyperimmune globulin provides the selection pressure. In these patients, HBsAg negativity does not exclude infection of the transplanted liver.- - - - - - - - - - ranking = 3.5keywords = antigen (Clic here for more details about this article) |
8/275. Oligoclonal immunoglobulin heavy-chain and T-cell receptor delta rearrangements persist in a recurrent acute lymphoblastic leukemia with one immunoglobulin kappa rearrangement as a clonal marker.Acute lymphoblastic leukemias (ALLs) represent the clonal expansion of a lymphoid precursor cell. Therefore, all cells of an ALL should have identical antigen receptor gene rearrangements. In a patient with diploid ALL of the B-cell precursor immunophenotype, seven different clonal rearrangements of the immunoglobulin heavy-chain genes (IgH) were identified, implying the presence of oligoclonal populations. All of these rearrangements were only detectable after a modification of the polymerase chain reaction for the complementarity determining region of the IgH genes using V(H) gene framework 3 and (H) consensus primers. sequence analysis showed that these rearrangements were completely unrelated to each other. Only two of these rearrangements were detectable by Southern blot analysis. Quantification and single-cell analysis confirmed the high frequency of these latter two rearrangements, as well as their presence in the same clonal population. The other rearrangements characterized less than 5% of the leukemic population. In addition, two T-cell receptor Vdelta2-Ddelta3 (TCRdelta) rearrangements were identified, both at a similar frequency. However, they were derived from different cells. An Igkappa rearrangement represented the only clonal marker in this leukemia. All of the Ig and TCRdelta rearrangements, with the exception of one IgH rearrangement, remained stable throughout the course of the disease. The persistence of such a great number of distinct IgH rearrangements at different quantities within the leukemic population and of the two biclonal TCRdelta rearrangements is compatible with the presence of a clonal disease that is defined by the Igkappa rearrangement.- - - - - - - - - - ranking = 0.5keywords = antigen (Clic here for more details about this article) |
9/275. Unusual presentation of graft-versus-host disease in pediatric liver transplant recipients: evidence of late and recurrent disease.Graft-versus-host disease (GvHD) is a multi-organ disease caused by mature donor T cells that are activated by alloantigens expressed by the host antigen-presenting cells. GvHD has been reported after solid organ transplantation with two principal presentations: humoral and cellular. In the cellular type of GvHD after liver transplantation the symptoms are identical to the GvHD after bone marrow transplant, except that the liver is spared because it lacks host antigens. We have described three cases of intestinal GvHD after pediatric liver transplant with an unusual recurrent late presentation in two patients. Two patients were female, and their age at the time of transplant was 8 and 9 months, respectively, and one was an 8-month-old male. They all received reduced liver allografts of identical blood type from three different donors. One patient received two doses of donor bone marrow cell infusion. Two patients received double immunosuppressive therapy constituted by tacrolimus at a dose of 0.05 mg/kg p.o. b.i.d. and steroids 10 mg p.o. daily. One patient received a triple drug immunosuppression with tacrolimus (0.05 mg/kg p.o. b.i.d.), steroids (10 mg p.o. daily) and mycophenolate mofetil (125 mg p.o. b.i.d.). diagnosis of intestinal GvHD was confirmed histologically on intestinal biopsies performed at the time of presentation of the clinical symptoms or at autopsy.- - - - - - - - - - ranking = 1.5keywords = antigen (Clic here for more details about this article) |
10/275. Absence of MHC class II gene expression in a patient with a single amino acid substitution in the class II transactivator protein CIITA.We investigated the underlying genetic defect in an immunodeficient patient who presented with recurrent bacterial infections in his late twenties and demonstrated a transcriptional defect in major histocompatibility complex (MHC) class II regulation. Transient heterokaryon analysis implicated functional loss of CIITA, the MHC class II transactivator protein, and in support of this MHC class II antigen expression was restored by stable transfection with the wild-type molecule. A single amino acid substitution, phenylalanine to serine, in the COOH-terminal portion of the CIITA sequence correlated with reduced transcription of both classical (HLA-DP, -DQ, and -DR) and nonclassical (HLA-DM and -DO) class II genes. The long survival of the patient, although remarkable, was not associated with partial CIITA function as evidenced by residual MHC class II expression. These data define at high resolution a region of CIITA that is essential for function in both professional and nonprofessional antigen presenting cells and which could potentially constitute a target for therapeutic intervention by novel factors with a propensity to downregulate MHC class II antigen expression.- - - - - - - - - - ranking = 1.5keywords = antigen (Clic here for more details about this article) |
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