Lymphocyte-predominance Hodgkin's disease.
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B-Lymphocytes↗
Biomedical subjects
S Poppema
Publications and source records attributed to S Poppema.
Biology of Hodgkin's disease.
The biology of Hodgkin's disease is one of the most intriguing subjects in lymphoma research. The presence of only a small proportion of neoplastic cells and a vast majority of reactive cells reflects the presence of complex interactions between these cell types. In this paper we discuss findings indicating that Reed-Sternberg cells may be virally transformed cells that have evaded a cytotoxic immune response and induce an ineffective delayed type hypersensitivity reaction.
Cell Transformation, Viral↗
Active immunization of human ovarian cancer patients against a common carcinoma (Thomsen-Friedenreich) determinant using a synthetic carbohydrate antigen.
In a phase I study, ten ovarian cancer patients with extensive metastatic disease despite chemotherapy were immunized three to eight times subcutaneously with the synthetic form of the immunodominant disaccharide (beta Gal1----3 alpha GalNAc) of the Thomsen-Friedenreich antigen conjugated to KLH (TF alpha-KLH) plus DETOX adjuvant. Six patients were given a "low" dose of TF alpha-KLH (100 micrograms/injection) and four patients were given a "high" dose (500 micrograms/injection). All patients received a single low-dose cyclophosphamide treatment (200 mg/m2 i.v.) 3 days prior to commencement of the series of immunizations. Immunizations were 2 weeks apart. Little or no toxicity was noted. As expected, all patients (prior to immunization) had naturally occurring IgM antibodies against the synthetic TF alpha hapten. None of the patients had detectable pre-existing IgG or IgA antibodies against synthetic TF alpha hapten. Nine of the ten ovarian cancer patients showed a significant increase in IgM titer above pre-existing levels following immunizations with TF alpha-KLH plus DETOX adjuvant. These same patients also produced IgG anti-TF alpha and eight of these also produced IgA anti-TF alpha, although the IgA responses were weaker. Most of the IgG responses followed the IgM responses by 2-4 weeks. Two patients produced a vigorous IgG response after their first TF alpha-KLH injection, suggesting a recall response. Both direct ELISAs on various solid-phase synthetic carbohydrate antigens and hapten inhibition experiments confirmed the TF alpha hapten specificity of the antibodies. IgM and IgG anti-TF alpha-specific antibodies reacted with natural TF antigen, by ELISA and FACS analysis, although the titers were generally lower than the titers against the immunizing TF alpha hapten. Increased levels of cytotoxic antibodies against TF-expressing tumor cell targets were detected in eight of the ten patients following immunization. One patient who had no detectable cytotoxic antibodies prior to immunization developed increasingly strong cytotoxic antibodies as a function of the number of immunizations. The low antigen dose patients showed as good or better humoral immune responses than the high antigen dose patients. All four high-dose and four of six low-dose patients developed moderate to strong DTH reactions at the vaccination sites. Our results demonstrate that KLH is an acceptable carrier for carbohydrate haptens in humans and that DETOX is an appropriate nontoxic adjuvant for the generation of high-titer specific anti-carbohydrate responses in human cancer patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adenocarcinoma↗
Inhibition of alloreactivity in vitro by monoclonal antibodies directed against restricted isoforms of the leukocyte-common antigen (CD45).
The leukocyte common antigen (LCA) is a protein tyrosine phosphatase and is identified by the CD45 cluster of monoclonal antibodies. CD45 is expressed in high-density on cells of hematopoietic lineage and generally is immunoprecipitated as 4 bands (220, 205, 190, and 180 KDa). Genetic studies have shown that a single gene produces additional forms of the molecule by alternate splicing including CD45RA (220, 205), CD45RO (180), and CD45RB (220, 205, 190). We have prepared a CD45RB Mab termed "MT3" that binds to a sialic acid dependent epitope. Since the LCA is one of the major targets of antilymphocyte globulin, we assessed a panel of CD45 and CD45R Mab for their ability to inhibit alloreactivity in vitro. MT3 (CD45RB) inhibits the allogeneic MLR and inhibits CD4+ T cells from expressing interleukin 2 receptors, and prevents CD4+ CD45RA- T cells from entering the proliferative phase of the cell cycle. Mem 93 (CD45RA) inhibits the generation of cytotoxic T cells. These data suggest that the CD45RB and CD45RA isoforms of the LCA may be appropriate targets for in vivo immunotherapy.
Antibodies, Monoclonal↗
Neoplastic changes involving follicles: morphological, immunophenotypic and genetic diversity of lymphoproliferations derived from germinal center and mantle zone.
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Antigens, CD↗
Lymphocyte-predominance Hodgkin's disease.
Nodular lymphocyte-predominance Hodgkin's disease (NLPHD) has emerged as a distinct entity. It has a precursor lesion, known as follicular hyperplasia with progressively transformed germinal centers (PTGC), and a late stage consisting of transformation to a large cell lymphoma. All cellular components of NLPHD are derived from follicles, but so far no clonal population has been identified.
B-Lymphocytes↗
Reactivity of monoclonal antibody B-ly7 with a subset of activated T cells and T-cell lymphomas.
Antibody B-ly7 is reactive with hairy cell leukemia and a small subpopulation of normal lymphocytes. The B-ly7 antigen can also be induced on normal peripheral blood lymphocytes by phorbol ester stimulation. Recently it has been found that the reactivity pattern of B-ly7 is similar to that of HML-1, an antibody reactive with mucosal T lymphocytes and so called enteropathy associated T-cell lymphomas. Reactivity of B-ly7 with 6/61 peripheral T-cell lymphomas, including two intestinal and four extraintestinal cases, is described. The intestinal cases were CD8 and CD7 positive, whereas the extraintestinal cases were CD4 positive and CD7 negative. Activation of purified peripheral blood T cells resulted in approximately 20% B-ly7+ T cells at Day 3. Approximately 75% of the B-ly7+ cells were CD8+, whereas the remainder were CD4+. The results indicate that B-ly7 as well as HML-1 recognize an activation-associated antigen that is expressed on small normal T-cell and B-cell populations and can be induced on a relatively high proportion of T and B cells in vitro.
Adult↗
Immunophenotype of Reed-Sternberg cells.
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Antigens, Surface↗
Antibody MT3 is reactive with a novel exon B-associated 190-kDa sialic acid-dependent epitope of the leukocyte common antigen complex.
MT3 is a new antibody reactive with a restricted isoform of the leukocyte common Ag (CD45) family. The Ag is mainly expressed on T lymphocytes and thymocytes. It is differentially expressed on B cell subpopulations, with no staining of the majority of small follicular mantle zone B cells but positive staining of the majority of marginal zone B cells of spleen. Like most CD45 antibodies, reactivity can be demonstrated in fresh frozen as well as in formalin-fixed, paraffin-embedded tissues. This reactivity clearly differs from all other published anti-CD45 antibodies. In immunoprecipitation and Western blot procedures, the antibody reacts with a major band with a molecular mass of 190 kDa and weak bands with molecular masses of 205 and 220 kDa. Compared to antibody PD7 that reacts with exon B-encoded sequences, the reactivity with the 205 and 220 bands is much weaker. This is reflected in MT3 reactivity with leukocyte common Ag transfectants that include exon B-encoded sequences, such as AB and B, but not with those that also include C-encoded sequences, such as ABC or BC. It can be concluded that MT3 recognizes additional heterogeneity in the leukocyte common Ag complex, that is based on the differential expression of sialic acid-dependent determinants associated with exon B-encoded sequences.
Antibodies, Monoclonal↗
Tissue distribution of the C3d/EBV-receptor: CD21 monoclonal antibodies reactive with a variety of epithelial cells, medullary thymocytes, and peripheral T-cells.
The CD21 antigen has been described to represent CR2, the receptor for the complement fragment C3d and also the receptor for the Epstein-Barr virus (EBV). Monoclonal antibodies B2, HB5, and B-ly4 belong to the CD21 cluster, recognizing different epitopes of the CD21-molecule. Immunohistology of lymphoid tissues employing these antibodies showed the known staining of B cells and dendritic reticulum cells. Surprisingly, B2, but not HB5 or B-ly4, stained a distinct spot in the cytoplasm of a major proportion of medullary thymocytes, in almost all peripheral blood lymphocytes, and in a substantial amount of cells in T-cell areas of peripheral lymphoid tissues. This distinct cytoplasmic B2 staining was confirmed by immuno-electronmicroscopy. A similar B2+ cytoplasmic dot was observed in B-lymphoblastic lymphomas. Staining of non-lymphoid tissues showed reactivity with all three CD21 mAb with epithelial cells of skin, lung, esophagus, jejunum, colon, pancreas, tonsil, adrenal cortex, renal tubuli, and parotid glands, and with hepatocytes and tongue muscle. In addition, endothelial cells of small vessels showed B2 staining. One possible explanation for our results is, that apart from the presence of B cells and follicular dendritic cells, a CD21-molecule may be expressed by other cell types. However, a maybe more likely explanation may be that the recognized epitopes are not exclusively associated with the C3d/EBV-receptor, but also with other structures. In particular should the possibility be recognized of cross-reactivity with CR2-related proteins, encoded by the large gene family, to which CR2 belongs.
Antibodies, Monoclonal↗
Automated procedure for dewaxing and rehydration of paraffin-embedded tissue sections for DNA flow cytometric analysis of breast tumors.
Flow cytometric DNA analysis of paraffin-embedded tumors is an important diagnostic and prognostic tool in clinical pathology. The technique is limited, however, by the time-consuming multistep procedure for dewaxing and rehydrating tissue. The authors developed an automated procedure to complete the dewaxing and rehydration of tissue using a routine histologic tissue processor with a 24-hour timer. This technique provided excellent tissue recovery and reproducible DNA histograms comparable to those obtained by manual methods. Subsequently, the authors analyzed the DNA content of 93 paraffin-embedded breast cancer tissues. The automation of a significant portion of the routine processing required for paraffin-embedded tissue makes cytometric DNA analysis a more practical procedure in the laboratory.
Automation↗
Restricted V gene usage in T-cell lymphomas as detected by anti-T-cell receptor variable region reagents.
Monoclonal antibodies reactive with variable regions of the human T-cell receptor (TCR) may be used to detect populations of T lymphocytes with restricted V gene usage. The authors have studied a series of 44 T-cell lymphomas with a panel of seven reagents reactive with four different TCR beta-chain variable region families. The authors found that, with this limited panel, restricted V gene usage of the neoplastic cells could be demonstrated in 29% of TCR-positive lymphomas. Whereas this is somewhat higher than expected, no preferential use of specific families could be demonstrated. An additional, unexpected finding was that most large cell T-cell lymphomas did not express TCR despite the presence of cytoplasmic CD3. The findings indicate that with a somewhat expanded panel it should be feasible to demonstrate restricted V gene usage as an indicator of clonality in a majority of T-cell lymphomas in a manner similar to the application of anti-immunoglobulin subclass antibodies in the diagnosis of clonal B cell proliferations.
Antibodies↗
Small lymphocytic lymphomas with predominant splenomegaly: a comparison of immunophenotypes with cases of predominant lymphadenopathy.
In this study, we compared small lymphocytic lymphomas with predominant lymphadenopathy with those with predominant splenomegaly and found differences in morphology and immunophenotype as well as clinical features. Cases with lymphadenopathy were characterized by widespread disease, CLL type morphology with proliferation centers, and a CD5, CD11c, CD23, CD43 positive, CD45Ro negative immunophenotype. Cases with predominant splenomegaly had more localized disease, a mantle zone pattern or a diffuse growth pattern without proliferation centers, and a CD5, CD11c, CD23, CD43 negative, and sometimes CD45Ro positive immunophenotype. CD45Ro (UCHL1) positivity and alkaline phosphatase staining were associated with a mantle zone growth pattern. Comparison with other small lymphocytic lymphoma subtypes indicated that each has its own specific immunophenotype.
Aged↗
HML-1 antigen on mucosa-associated T cells, activated cells, and hairy leukemic cells is a new integrin containing the beta 7 subunit.
The monoclonal antibodies HML-1, B-ly7 and Ber-ACT8 recognize intramucosal gut T lymphocytes, activated cells, and hairy cell leukemia. The antigen on hairy cells consists of three glycoproteins (160 kappa D, 130 kappa D and 105 kappa D unreduced; 145 kappa D and 120 kappa D reduced). These peptides have biochemical features reminiscent of integrins but we have shown by immunoprecipitation that they are not known integrin subunits. We have used a newly produced antibody (BP6) to purify this molecule and shown by N-terminal sequence analysis that the smallest subunit is the product of integrin beta 7 cDNA. This molecule is thus a new member of the integrin family of leucocyte adhesion proteins. Immunoprecipitation experiments indicate that the two larger subunits are recognized by HML-1, B-ly7 and Ber-ACT8.
Amino Acid Sequence↗
Tissue distribution of restricted leukocyte common antigens. A comprehensive study with protein- and carbohydrate-specific CD45R antibodies.
A panel of monoclonal antibodies, specific for either protein or carbohydrate components of the leukocyte common antigen (LCA), were used to characterize the expression pattern of different variants of this antigen complex. Immunohistochemical and flow cytometric analysis was carried out on human lymphoid tissues from different anatomical compartments. We found that variations in terminal sialic acid or O-linked sugar moieties were associated with drastic differences in reactivity with some of the CD45R antibodies. For example, the carbohydrate determinants recognized by MT2 (CD45RA) and 2B11 (CD45) were not or were very weakly expressed on germinal center cells, whereas the carbohydrate determinant recognized by MT3 (CD45RB) was not expressed on the majority of mantle zone B cells. On the other hand, KiB3 (CD45RA) reacted with a protein determinant that is normally only exposed on mantle zone B cells but can be uncovered on marginal zone B cells and the CD45RA-positive T-cell subpopulation by enzymatic treatment. The findings suggest that differential biosynthesis and expression of the carbohydrate components of LCA are important mechanisms to generate additional LCA heterogeneity. Similar to the differential usage of the variable region, the exact carbohydrate composition is also linked to the stage of cell development. Heterogeneity in carbohydrate composition of the extracellular domain of LCA appears to enable interactions with different ligands, thereby holding the key to the regulation of LCA cytoplasmic tyrosine phosphatase activity.
Antibodies↗
Monoclonal antibody OPD4 is reactive with CD45RO, but differs from UCHL1 by the absence of monocyte reactivity.
Monoclonal antibody OPD4 was described as a novel monoclonal antibody recognizing a helper/inducer T-cell subset in paraffin-tissue sections. The authors have analyzed this reagent with respect to its molecular weight, reactivity with leukocyte common antigen (LCA) transfectants and cell and tissue distribution. OPD4 was found to be reactive with the 180 kd molecular weight isoform of the leukocyte common antigen family, similar to antibody UCHL1 and therefore can be considered as a CD45RO reagent. The only difference in distribution was found to be the absence of OPD4 reactivity with peripheral blood monocytes. Since OPD4 recognizes the same antigen on T cells as UCHL1, both reagents do not need applied in the immunophenotyping of lymphomas.
Animals↗
Primary breast lymphoma. An immunohistologic study of 20 new cases.
Primary malignant lymphomas of the breast (PBL) are uncommon. The authors report the clinical, histologic, and immunoperoxidase findings on 20 cases recorded at the Alberta Cancer Registry over the last 23 years. These cases were then added to material on 257 cases abstracted from the literature and analyzed. It was found that there are two clinicopathologic types of PBL. The first affects pregnant or lactating women with bilateral, diffuse disease, is rapidly fatal, and corresponds histologically to a Burkitt's-type lymphoma. The second is unilateral at presentation and afflicts a broad age range, but primarily older women. This has a variable course only part of which is predicted by histologic grade and stage. Tumor size, treatment, and side of presentation were not found to be significant prognostic factors. Histologically, these tumors can be grouped into large cell B-cell lymphomas, monocytoid B-cell lymphomas (MBCL), and undifferentiated, some of which may be T-cell. Evidence suggesting that the MBCL of breast are the equivalent of the malignant lymphomas of the mucosa-associated lymphoid tissues (MALT) is reviewed. The breast is a hormone-dependent member of the MALT and therefore it is interesting that two of these tumors were strongly positive for estrogen receptors.
Adolescent↗
B-ly-7, a monoclonal antibody reactive with hairy cell leukemia, also defines an activation antigen on normal CD8+ T cells.
We undertook a study to determine the specificity of the monoclonal antibody, B-ly-7, for hairy cell leukemia (HCL) by examining the expression in 150 samples from B-cell lymphoproliferative diseases as well as screening for reactivity in a number of other hematologic malignancies. Within the B-cell lineage we found that the expression of B-ly-7 was highly specific for HCL and reacted with all 28 cases examined, as well as with 3 of 9 cases of a variant form of HCL. Cells of other closely related B-cell disorders, prolymphocytic leukemia, and splenic lymphoma with villous lymphocytes were negative. Investigation of the peripheral blood and bone marrow of patients with HCL before and after treatment with alpha-interferon or deoxycoformycin suggests that B-ly-7 may be useful in the assessment of minimal disease after therapy. In addition to HCL, we found that B-ly-7 was positive with cells of three mature, CD4+ T-cell malignancies. In view of the reactivity with malignancies of activated B and T cells, we searched for the expression of B-ly-7 on activated, normal B and T cells and found that B-ly-7 reacted specifically with activated normal peripheral blood CD8+ T cells. B-ly-7 has a number of applications, including the precise classification of mature B-cell neoplasia and the diagnosis HCL and its assessment after treatment. In addition, B-ly-7 recognizes a small subset of T-cell disorders. Its expression on these malignancies and on in vitro activated peripheral blood CD8+ T cells suggests that B-ly-7 detects a lymphocyte activation antigen.
Antibodies, Monoclonal↗