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S Poppema

Publications and source records attributed to S Poppema.

At least 19 recordsLinked to original sources
PubMed1999

Mechanisms of induction of renal allograft tolerance in CD45RB-treated mice.

BACKGROUND: Rejection is the most significant problem in the field of transplantation. The current goal of transplant immunology is to develop better immunotherapeutic protocols that are aimed at specifically suppressing alloreactivity and preserving an otherwise intact immune system. We have previously shown that mice will accept renal allografts indefinitely with normal renal function after two injections of a monoclonal antibody to the CD45RB protein. Furthermore, this antibody will reverse acute rejection when therapy is delayed until day 4 and will still induce tolerance. The mechanisms of this therapeutic benefit are not known. METHODS: BALB/C mice were used as recipients of major multiple histocompatibility complex-mismatched kidneys using C57BL/6 as donors. Immunoperoxidase microscopy and Northern blots for cytokine gene expression were used to study the renal allografts. Fluorescence-activated cell sorter (FACS) analyses of peripheral blood lymphocytes were performed. Phosphotyrosine peptide phosphatase assays were performed on splenic lymphocyte membranes. RESULTS: A CD45RB monoclonal antibody (MB23G2) induced tolerance and partially depletes peripheral blood lymphocytes. A therapeutically ineffective CD45RB monoclonal antibody (MB4B4) merely coated the circulating lymphocytes. Furthermore, MB23G2 stimulated more tyrosine phosphatase activity than MB4B4 in mouse T-cell membranes. CONCLUSIONS: The clearance of peripheral blood lymphocyte populations and stimulation of protein tyrosine phosphatase activity may be important in the mechanism of tolerance induction by CD45RB therapy, which may be clinically relevant in the therapy of organ rejection in humans.

Animals↗
PubMed1999

Clinical presentation, course, and prognostic factors in lymphocyte-predominant Hodgkin's disease and lymphocyte-rich classical Hodgkin's disease: report from the European Task Force on Lymphoma Project on Lymphocyte-Predominant Hodgkin's Disease.

PURPOSE: Recent studies have suggested that lymphocyte-predominant Hodgkin's disease (LPHD) is both clinically and pathologically distinct from other forms of Hodgkin's disease, including classical Hodgkin's disease (CHD). However, large-scale clinical studies were lacking. This multicenter, retrospective study investigated the clinical characteristics and course of LPHD patients and lymphocyte-rich classical Hodgkin's disease (LRCHD) patients classified according to morphologic and immunophenotypic criteria. MATERIALS AND METHODS: Clinical data and biopsy material of all available cases initially submitted as LPHD were collected from 17 European and American centers, stained, and reclassified by expert pathologists. RESULTS: The 426 assessable cases were reclassified as LPHD (51%), LRCHD (27%), CHD (5%), non-Hodgkin's lymphoma (3%), and reactive lesion (3%); 11% of cases were not assessable. Patients with LPHD and LRCHD were predominantly male, with early-stage disease and few risk factors. Patients with LRCHD were significantly older. Survival and failure-free survival rates with adequate therapy were similar for patients with LPHD and LRCHD, and were stage-dependent and not significantly better than stage-comparable results for CHD (German trial data). Twenty-seven percent of relapsing LPHD patients had multiple relapses, which is significantly more than the 5% of relapsing LRCHD patients who had multiple relapses. Lymphocyte-predominant Hodgkin's disease patients had significantly superior survival after relapse compared with LRCHD or CHD patients; however, this was partly due to the younger average age of LPHD patients. CONCLUSION: The two subgroups of LPHD and LRCHD bore a close clinical resemblance that was distinct from CHD; the course was similar to that of comparable nodular sclerosis and mixed cellularity patients. Thorough staging is necessary to detect advanced disease in LPHD and LRCHD patients. The question of how to treat such patients, either by reducing treatment intensity or following a "watch and wait" approach, remains unanswered.

Adult↗
PubMed1998

Antibody-mediated targeting of CD45 isoforms: a novel immunotherapeutic strategy.

CD45 is a family of transmembrane protein tyrosine phosphatases exclusively expressed by hematopoietic cells and critically involved in the regulation of T cell activation signals. We now demonstrate that three 100-microg doses of anti-CD45RB mAb MB23G2 can induce long-term engraftment of islets into major histcompatibility complex-disparate chemically diabetic mice. Long-term graft survivors (>120 days) were tolerant to new islet allografts from the original donor strain. MB23G2 induced a temporary decrease in number circulating leukocytes but had no effect on leukocyte number in other lymphoid compartments. Histologic examination of allografts from treated and untreated recipients revealed a similar peri-islet infiltration on day 6. Eleven days after transplant, the peri-islet infiltrate in treated animals persisted, but in marked contrast to untreated control animals, there was no insulitis and islet integrity was preserved. The peri-islet infiltrate from treated animals showed a mild increase in CD4 cells, a decrease in CD8 cells, and decreased intensity of CD45RB expression. Treatment of naive animals with anti-CD45RB (MB23G2) resulted in a shift in CD45 isoform expression on T cells with a loss of higher molecular weight isoforms and increased expression of lower molecular weight (CD45R0) isoform. This shift in CD45 isoform expression from CD45RBHi to CD45RBLo was associated with an increase in the intragraft expression of transcripts for interleukin (IL) 4 and IL-10, consistent with the expected activity of this distinct immunoregulatory T cell subset. Antibody-mediated targeting of CD45 may induce tolerance through novel mechanisms and have direct applicability to clinical transplantation in humans.

Animals↗
PubMed1998

Ischaemic colitis and lung infiltrates caused by extramedullary haematopoiesis in a patient with an acute erythroid leukaemia following polycythaemia vera.

A patient with 'spent' polycythaemia vera showed extensive extramedullary haematopoiesis (EMH) in non-haematopoietic tissue clinically resulting in an ischaemic colitis and respiratory symptoms due to lung infiltrates. On laboratory investigation, the EMH also included immature erythroblasts due to acute erythroid leukaemia. It is hypothesised that the abnormal homing of erythroid progenitors might be related to the abnormal expression of antigens, such as CD36.

Aged↗
PubMed1998

Immune escape mechanisms in Hodgkin's disease.

BACKGROUND: The nodular sclerosis and mixed cellularity subtypes of Hodgkin's disease are histologically characterised by a small population of neoplastic cells, the so-called Reed-Sternberg cells and their mononuclear variants (RS cells) and an extensive admixture of other cell types including lymphocytes, plasma cells, eosinophils, and histiocytes. The nature of this infiltrate is largely known, but the mechanisms and functional effects are not. The small lymphocytes immediately surrounding the RS cells are mostly CD4+ T cells that express early activation markers. The absence of prominent specific cytotoxic T cell or natural killer (NK) cell populations seems to argue against a Th1-type response, whereas the sometimes prominent admixture of plasma cells and eosinophils is suggestive of a Th2-type response. Enrichment of the CD4 T-cell population may result from selective influx of CD4 T cells or from selective depletion of CD8 and NK cells. RESULTS AND DISCUSSION: The T cells surrounding RS cells have an immuno-phenotype and cytokine production capability consistent with a Th2-type response. RS cells express several members of the TNF receptor family such as the FAS ligand (CD95L) that may induce apoptosis of activated, FAS expressing, CD8+ T cells and NK cells. The RS cells also produce TGF beta and interleukin-10 that may downmodulate the Th1 response. In addition, the Reed-Sternberg cells produce the chemokine TARC that could lead to the specific attraction of a Th2 T-cell subset. CONCLUSION: RS cells have several mechanisms that may allow it to escape an effective immune response. The relative contributions of each of these and other potential mechanisms are not yet known.

CD4 Antigens↗
PubMed1998

Workshop report on Hodgkin's disease and related diseases ('grey zone' lymphoma).

Despite advances in immunohistochemistry and molecular biology, the distinction between classical Hodgkin's lymphoma and related diseases such as nodular lymphocyte-predominant Hodgkin's disease, T-cell rich large B-cell lymphoma or anaplastic large cell lymphoma has remained difficult in rare cases. Lack of clear-cut diagnostic criteria represents a problem for both the pathologist and the clinician. To delineate this 'grey zone' between classical Hodgkin's lymphoma and non-Hodgkin's lymphoma (NHL) and to develop criteria for classification of such cases, 12 expert hematopathologists each submitted one to five borderline cases to a workshop. Cases were reviewed and classified at a multiheaded microscope and criteria were established for the diagnosis of questionable cases. Well established entities such as classical Hodgkin's lymphoma, anaplastic large-cell lymphoma and TCRBCL were defined more strictly and cases with unusual morphology or antigen expression could be identified. A distinctive subset of cases representing mediastinal large B-cell lymphomas with features of Hodgkin's lymphoma was identified.

Diagnosis, Differential↗
PubMed1998

bcl-1 gene rearrangements in mantle cell lymphoma: a comprehensive analysis of 118 cases, including B-5-fixed tissue, by polymerase chain reaction and Southern transfer analysis.

We evaluated 118 cases of mantle cell lymphoma by polymerase chain reaction (PCR) for the major translocation cluster (MTC) region and another breakpoint corresponding to probe p94PS, located 24 kb telomeric to the MTC locus on chromosome 11. The specimens included 64 frozen, 19 formalin-fixed, and 9 B-5-fixed lymph nodes and 26 B-5-fixed bone marrow biopsy specimens. We also analyzed DNA from the 64 frozen lymph nodes by Southern transfer analysis (SB) using three separate bcl-1 breakpoint probes. Gene rearrangements were identified in 17 (PCR) and 18 (SB) of 64 frozen lymph nodes and by PCR in 6 of 19 formalin-fixed lymph nodes, 3 of 9 B-5-fixed lymph nodes, and 12 of 26 B-5-fixed bone marrow cores with MTC locus primers and probe. Only one case showed rearrangement with the p11EH probe that corresponds to breakpoints situated 63 kb telomeric to the MTC locus. No rearrangements were detected by PCR or SB for the breakpoint site corresponding to the p94PS probe, but we identified a polymorphic restriction site with HinD III digest in approximately 25% of the cases. In agreement with other studies, these results confirmed that breakpoints in the MTC region of the bcl-1 locus are tightly clustered and associated with 30 to 40% of mantle cell lymphomas. Other breakpoints in the bcl-1 locus seem to be heterogeneous and cannot be detected by PCR or SB with use of existing probes or primer sequences. The most important finding of our study is optimization of the methodology for the detection of immunoglobulin heavy chain gene rearrangement and MTC region breakpoints by PCR from the DNA isolated from B-5-fixed, paraffin-embedded lymph nodes and bone marrow biopsy specimens. The results obtained from these tissues are comparable to those obtained from frozen or formalin-fixed tissue.

Blotting, Southern↗
PubMed1996

Continuous administration of Il-13 to mice induces extramedullary hemopoiesis and monocytosis.

IL-13, a recently identified Th2 cytokine, shares some, but not all, IL-4 functions, including inhibition of monocyte and macrophage activation, stimulation of human B cells, and induction of growth and differentiation of mouse bone marrow cells in vitro. We have now tested the in vivo effects of recombinant mouse IL-13 (rIL-13) from stably transfected, high expressing BW5147 thymoma cells. After purification by anion exchange chromatography, rIL-13 was administered in the peritoneal cavity of BALB/c mice via osmotic pump for 7 days. Spleens from the rIL-13-treated mice were significantly enlarged compared with control spleens due to increased cellularity. In particular, increased numbers of immature erythroblasts and megakaryocytes were observed in splenic sections after rIL-13 treatment. Spleen cells from rIL-13-treated mice showed greatly increased responsiveness in vitro to recombinant forms of mouse IL-3, mouse granulocyte-macrophage CSF, or human CSF-1 and, to a lesser extent, to mouse IL-4 or IL-13. Moreover, the rIL-13-treated mice also showed significant increases in CFU-E, CFU-C, and erythroid burst colonies in the spleen, further indicating the presence of increased numbers of hemopoietic precursors. Hematologic analyses indicated that rIL-13 treatment induced slight anemia and striking monocytosis. Finally, spleen cells from rIL-13-treated mice produced significantly more IL-6 upon LPS stimulation. Interestingly, the strong Th2 response induced by Nippostrongylus brasiliensis infection was also accompanied by an increase in hemopoietic precursor frequencies in the spleen. Collectively, these data indicate that exogenous rIL-13 induces extramedullary hemopoiesis in mice and suggest that endogenous IL-13 may contribute to replenishment of effector cells during strong Th2 responses.

Anemia↗
PubMed1996

Prevention and reversal of renal allograft rejection by antibody against CD45RB.

Rejection continues to be the single largest impediment to successful organ transplantation. Antilymphocyte globulin, which contains antibodies that react with the leukocyte common antigen known as CD45, has proved to be one of the most effective agents for preventing rejection. We have shown earlier that a monoclonal antibody directed against the RB isoform of CD45 substantially inhibits the alloreactivity of human CD4+ lymphocytes in vitro. Here we investigate whether CD45RB could be an appropriate target for preventing renal allograft rejection in mice. Mice treated with two injections of a monoclonal antibody (MB23G2) raised against CD45RB protein all survived and had normal renal function. Furthermore, this antibody reversed acute rejection when therapy was delayed until day 4, and the mice survived for their natural lifespan. The immunosuppression achieved may find application in the prevention and treatment of transplant rejection in man.

Animals↗
PubMed1996

A pathologic study of Hodgkin's disease in Korea and its association with Epstein-Barr virus infection.

BACKGROUND: The incidence of Hodgkin's disease (HD) in Korea and other Asian countries is much lower than in western countries and its association with the Epstein-Barr virus has not been well characterized. METHODS: We evaluated the clinical, morphologic, and immunohistochemical features of 87 patients with Hodgkin's disease and also analyzed patients for Epstein-Barr virus (EBV) using in situ hybridization for EBV DNA, RNA, and latent membrane protein (LMP1). RESULTS: There were 68 males and 19 females, with a mean age of 38 years. Mixed cellularity was the most prevalent subtype. Expression of EBV RNA (EBER:EBV-encoded RNA) was detected in 60 of 87 cases (69%): 1 of 1 (100%) with lymphocyte predominance, nodular; 4 of 7 (57%) with lymphocyte predominance, diffuse; 10 of 17 (59%) with nodular sclerosis; 38 of 51 (75%) with mixed cellularity; and 7 of 11 (64%) with lymphocyte depletion. Positivity was higher in advanced clinical stages; 4 of 7 patients (57%) with Stage I; 6 of 12 patients (50%) with Stage II: 7 of 9 patients (75%) with Stage III; and 5 of 5 patients (100%) with Stage IV HD EBV DNA was detected in 9 of 25 cases tested (36%). LMP1 was seen in 39 of 87 cases (45%). EBER and LMP1 positivity were higher in children and older adults than in adults aged between 15-50 years. Immediate early mRNAs (BHLF:Bam H-fragment, lower strand frame) was seen in a single patient. CONCLUSIONS: HD in Korea showed a high incidence of mixed cellularity subtype and a high prevalence of EBV. EBV was detected in all subtypes, including a case of nodular lymphocytic predominance, and in all age groups, and showed correlation with mixed cellularity subtype and higher clinical stage. The expression of EBER and LMP were more frequently seen in children and older adults, suggesting a lowered immune surveillance in those age groups or a different pathophysiology of HD among different age groups.

Adolescent↗
PubMed1996

Localization of cytosolic aldehyde dehydrogenase in the developing chick retina: in situ hybridization and immunohistochemical analyses.

Cytosolic aldehyde dehydrogenase (ALDH) mRNA is present at high levels in the undifferentiated chick retina. Tissue maturation is accompanied by a 20-25x decrease in transcript levels. To determine the spatial and temporal distribution pattern of the ALDH transcript and its encoded protein in the developing retina, in situ hybridization and immunohistochemical analyses were carried out using chick embryos at different stages of development. The ALDH transcript and protein were detected at the earliest stage tested, in the inner layer of the optic cup of stage 14 (day 2) embryos. Both the ALDH transcript and protein were found in the dorsal retina of chick embryos from stage 18 (day 3) to day 16 of incubation. Accumulation of the ALDH protein in the neurites of ganglion cells could readily be detected at early developmental stages. Staining of this ganglion fiber layer was strong in the dorsal retina and could be followed up to and into the optic nerve. By day 11, ALDH mRNA was located primarily in the ciliary margin and in the inner nuclear layer of the dorsal retina. In addition to these areas, the ALDH protein was also found in the inner plexiform and optic nerve fiber layers. These results suggest that environmental or transcriptional factors involved in the regulation of the ALDH gene are restricted to the dorsal retina at early developmental stages and that there is a requirement for the compartmentalization of the ALDH transcript/protein in the undifferentiated chick retina.

Aldehyde Dehydrogenase↗
PubMed1996

Pre-immunotherapy serum CA27.29 (MUC-1) mucin level and CD69+ lymphocytes correlate with effects of Theratope sialyl-Tn-KLH cancer vaccine in active specific immunotherapy.

Patients with metastatic breast, colorectal or ovarian cancers received active specific immunotherapy (ASI) with Theratope sialyl-Tn-KLH (keyhole limpet hemocyanin) cancer vaccine emulsified in Detox adjuvant. The median log2 anti-STn IgG titer generated by ASI, estimated by enzyme-linked immunosorbent assay with solid-phase ovine submaxillary mucin, was 5.322 (range = 0 - 9.322). Following ASI, 51 patients who generated titers higher than the median value for anti-STn+ mucin IgG survived longer than 46 patients who generated lower titers below the median. 38 of the patients were phenotyped for CD69 prior to ASI. The patients with lower numbers of CD69+ peripheral blood lymphocytes prior to immunotherapy (pre-ASI) also had low serum CA27.29 cancer antigen (MUC-1) levels, and had longer times to disease progression and improved survival following ASI. Elevated pre-ASI serum CA27.29 tumor antigen levels were associated with higher numbers of CD69+ PBL, with decreased anti-STn antibody production and decreased survival following ASI. The data are compatible with the hypothesis that elevated serum MUC-1 mucin is specifically immunosuppressive.

Antigens, CD↗
PubMed1996

Immunology of Hodgkin's disease.

Hodgkin's disease is characterized by an immune response in the involved tissues that is predominantly CD4 mediated. The CD4+ T-cells are CD45RO+ and CD45RBdim, they express several activation markers but lack CD26, and in vitro can be stimulated to produce gamma-interferon and IL-4, but not IL-2. This is not the usual immunophenotype and cytokine production pattern of Th1, Th2 or Th0 cells and may be a reflection of anergy. The cause of such an anergic reaction is not clear since RS cells express HLA class II as well as the co-stimulator molecules CD80 and CD86. It is possible that a (hypothetical) super antigen expressed on the RS cells may play a role. The absence of IL-2 production however explains the absence of a CD8 mediated response. In addition to that, RS cells generally do not express HLA class I, which allows them to escape CD8 mediated responses. The link between the ineffective immune response in the tissue and the generalized immune deficiency in Hodgkin's disease may consist of several components. These include the influx of mature T-cells into the affected tissues, the secretion of inhibitory molecules by the neoplastic cells and the spill-over of the anergic T-cell response into the general circulation by either the Hodgkin related antigen or also as a result of an IL-4 dominated response. The latter possibility may also be related to the hyper-gamma-globulinaemia and the frequently observed high IgE levels.

Antibody Formation↗
PubMed1996

CD45 (leucocyte common antigen) expression in T and B lymphocyte subsets.

CD45 is the dominant tyrosine phosphatase in haematopoietic cells and can modulate the effects of many other signaling molecules by dephosphorylation. The extracellular portion of CD45 has considerable variability due to differential splicing and glycosylation. This may allow for interactions with a variety of ligands expressed on interacting cells or on the same cell surface. Monoclonal anti CD45 antibodies that are reactive with epitopes that result from differential splicing and glycosylation can distinguish between cell populations that differ in maturation and function. These reagents can be used in the immunophenotyping of hematopoietic malignancies as well as in immunodeficiencies and autoimmune diseases. Several studies have shown that different anti CD45 reagents have different activating or inhibiting effects in vitro on a variety of T and B cell activation events. There are some indications that anti CD45 reagents can also selectively modify lymphocyte function in vivo. Such applications could potentially allow for the selective upregulation and down regulation of lymphocyte functions in a variety of immunologically mediated diseases.

B-Lymphocyte Subsets↗