Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019829 (Hodgkin's disease)
 30,247 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatitis C virus (HCV) is associated with B-cell lymphoproliferative disorders such as mixed cryoglobulinemia (MC) and B-cell non-Hodgkin lymphoma (B-NHL). The pathogenesis of these disorders remains unclear, and it has been proposed that HCV drives the pro-liferation of B cells. Here we demonstrate that certain HCV(+)MC(+) subjects have clonal expansions of immunoglobulin M (IgM)(+)kappa(+)IgD(low/-)CD21(low)CD27(+) B cells. Using RT-PCR to amplify Ig from these singly sorted cells, we show that these predominantly rheumatoid factor-encoding V(H)1-69/J(H)4 and V(kappa)3-20 gene segment-restricted cells have low to moderate levels of somatic hypermutations. Ig sequence analysis suggests that antigen selection drives the generation of mutated clones. These findings lend further support to the notion that specific antigenic stimulation leads to B-cell proliferation in HCV MC and that chronic B-cell stimulation may set the stage for malignant transformation and the development of B-NHL. The finding that these hypermutated, marginal zone-like IgM(+)CD27(+) B cells are clonally expanded in certain subjects with MC offers insight into mechanisms of HCV-associated MC and B-cell malignancy. This study was registered at www.clinicaltrials.gov as NCT00219999.
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PMID:Clonal expansion of immunoglobulin M+CD27+ B cells in HCV-associated mixed cryoglobulinemia. 1794 51

Epstein Barr virus (EBV) infection of human B lymphocytes in vitro results in immortalisation of the cells and augmented membranous expression of numerous B-cell activation molecules, including CD23. Other studies demonstrated that only those B lymphocytes which carry the surface CD21 (EBV receptor) become transformation-competent. Inspired by the relatively unclear relations between expression of EBV and those of CD21 and CD23 in in vivo conditions we have decided to define correlations between tissue markers of EBV and of CD21 and CD23 molecules in B-cell non-Hodgkin's lymphomas (NHLs) in children. The studies were performed on an archival tissue material originating from children with B-cell NHLs (n=26) using immunocytochemical techniques, in situ hybridisation, and PCR. Our studies confirmed the latent phase of EBV infection in all of the EBV-positive patients. Viral proteins as well as viral RNAs (EBERs) was found both in the cytoplasm, in cell nuclei and in cell membranes of mainly the transformed lymphocytes B. Expression of the latent proteins (EBNA2 and LMP1) and that of EBERs in B-cell NHLs was significantly higher as compared to children with nonneoplastic lesions. The studies demonstrated reciprocally positive correlations between expressions of CD21 and CD23 in our children, but no correlation could be demonstrated between expression of EBV tissue markers and that of CD21 and/or CD23. Positive correlation was confirmed between expression of EBNA2 and LMP1 as well as between expression of the two proteins and EBERs in B-cell NHLs. Our studies have shown mainly latency III pattern of EBV. We have also demonstrated a novel form of EBV latency with no EBERs expression. The high detectability of EBV-positive cases both in the group of B-cell NHLs (77%), and in the group with non-neoplastic lesions (64%) suggested that only more pronounced tissue expression of EBV markers in B-cell NHLs as compared to the non-neoplastic material may point to a potential role of EBV in pathogenesis of lymphoma in this group of population in our country.
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PMID:Epstein-Barr virus (EBV) infection in B-cell non-Hodgkin's lymphomas in children: virus latency and its correlation with CD21 and CD23 molecules. 1795 Nov 65

CD19 and CD21 (CR2) are co-receptors found on B-cells and various B-cell lymphomas, including non-Hodgkin lymphoma. To evaluate their suitability as targets for therapy of such lymphomas using internalization-dependent antibody-drug conjugates [such as antibody-4-(N-maleimidomethyl)cyclohexane-1-carboxylate, (N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine) (MCC-DM1) conjugates, which require lysosomal degradation of the antibody moiety for efficacy], we examined uptake of antibodies to CD19 and CD21 in a panel of B-cell lines. Anti-CD21 antibodies were not sufficiently internalized even in the highest CD21-expressing Raji cells, resulting in lack of efficacy with anti-CD21-MCC-DM1 conjugates. Anti-CD19 antibody uptake was variable, and was unexpectedly negatively correlated with CD21 expression. Thus, high CD21-expressing Raji, ARH77 and primary B-cells only very slowly internalized anti-CD19 antibodies, while CD21-negative or low expressing cells, including Ramos and Daudi, rapidly internalized these antibodies in clathrin-coated vesicles followed by lysosomal delivery. Anti-CD19-MCC-DM1 caused greater cytotoxicity in the faster anti-CD19-internalizing cell lines, implying that the rate of lysosomal delivery and subsequent drug release is important. Furthermore, transfection of Ramos cells with CD21 impeded anti-CD19 uptake and decreased anti-CD19-MCC-DM1 efficacy, suggesting that CD21-negative tumours should respond better to such anti-CD19 conjugates. This may have possible clinical implications, as anti-CD21 immunohistochemistry revealed only approximately 30% of 54 diffuse large B-cell lymphoma patients lack CD21 expression.
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PMID:High CD21 expression inhibits internalization of anti-CD19 antibodies and cytotoxicity of an anti-CD19-drug conjugate. 1799

The diagnosis of follicular dendritic cell (FDC) sarcoma can be challenging because of its morphologic overlaps with many other spindle cell neoplasms and, therefore, new phenotypic markers will be helpful in its differential diagnosis. Podoplanin is a mucin-type transmembrane glycoprotein that has recently been detected in reactive FDCs. In this study, we investigated the expression patterns of podoplanin using a new mouse monoclonal antibody D2-40, and compared them with CD21, a well-established FDC marker, in a comprehensive panel of cases. The panel included 4 FDC sarcomas, 38 spindle cell neoplasms of other types, 25 reactive lymphoid hyperplasia, and 117 lymphoid and 5 myeloid malignant hematopoietic neoplasms. Our study revealed that D2-40 strongly stained 3 of 4 FDC sarcomas. In contrast, D2-40 stained only 2/38 other spindle cell neoplasms tested. Furthermore, we observed that D2-40 highlighted more FDC meshworks than CD21 in Castleman's disease, follicular lymphoma, nodular lymphocyte predominance Hodgkin lymphoma, and residual reactive germinal centers in a variety of lymphoma types. D2-40 and CD21 stained an equal number of cases of reactive lymphoid hyperplasia, progressively transformed germinal centers and angioimmunoblastic T-cell lymphoma. No expression of podoplanin was detected in normal or neoplastic lymphoid and myeloid cells. We conclude that podoplanin (D2-40) is a sensitive and specific FDC marker, which is superior or equal to CD21 in evaluating both reactive and neoplastic FDCs. In addition, our results suggest that podoplanin (D2-40) can be used to support the diagnosis of FDC sarcoma.
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PMID:Podoplanin (d2-40): a new immunohistochemical marker for reactive follicular dendritic cells and follicular dendritic cell sarcomas. 1878 10

The monoclonal antibody D2-40 recognizes the membrane protein podoplanin, which is an established marker for germ cell tumors, mesotheliomas, and other tumor types and is also expressed in a variety of normal cells including follicular dendritic cells (FDCs). To determine whether podoplanin represents an effective FDC marker for pathologic lymph nodes, we compared immunohistochemical studies (sensitivity, staining patterns, and intensity of staining) for podoplanin (D2-40) with those of the traditional FDC markers CD21, CD35, and clusterin. Paraffin sections of 26 lymph nodes were analyzed, including 4 cases of nodular lymphocyte-predominant Hodgkin lymphoma, 4 angioimmunoblastic T-cell lymphoma, 8 follicular lymphoma (including 3 cases with a component of diffuse large B-cell lymphoma), 5 hyaline-vascular Castleman disease, and 5 reactive lymph nodes with follicular hyperplasia. In all cases, qualitatively and quantitatively podoplanin represented a highly effective marker for detection of FDCs, with staining intensity equal to or greater than that observed for other FDC markers. This study demonstrates that podoplanin is an excellent marker for FDCs and adds to its growing list of diagnostic applications.
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PMID:Podoplanin (D2-40) is a highly effective marker of follicular dendritic cells. 1883 18

Follicular lymphoid hyperplasia (FLH) of the palate is a very rare benign, proliferative process, with only 20 cases published so far in the English language literature. We describe a case, in a 55-year-old Caucasian female, who developed a swelling in the left posterior hard palate. Bony involvement was absent. Importantly, the medical history was positive for a previous non-Hodgkin lymphoma. Following incisional biopsy, histological examination revealed a vaguely nodular lymphoid proliferation composed of small well-differentiated lymphocytes. The lymphoid follicles were positive for CD20, CD79a, CD10, CD21 and BCL6, while negative for BCL2. The parafollicular areas revealed positivity for CD3, CD5, CD30, and CD15. Both areas were CD45 positive. Subsequent immunoglobulin heavy chain gene rearrangement analysis revealed a polyclonal lesion. No further treatment was instituted, and the patient is currently being followed-up every three months. This report demonstrates that FLHs are especially important due to their clinical and, occasionally, microscopic resemblance to follicular lymphomas. Morphologic and immunohistochemical analyses and molecular studies are essential to achieve accurate diagnosis and to implement appropriate management.
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PMID:Follicular lymphoid hyperplasia of the palate: case report and literature review. 1913 28

Despite major advances in the treatment of non-Hodgkin lymphoma (NHL), including the use of chemotherapeutic agents and the anti-CD20 antibody rituximab, the majority of patients eventually relapse, and salvage treatments with non-cross-resistant compounds are needed to further improve patient survival. Here, we evaluated the antitumor effects of the microtubule destabilizing agent monomethyl auristatin E (MMAE) conjugated to the humanized anti-CD19 antibody hBU12 via a protease-sensitive valine-citrulline (vc) dipeptide linker. hBU12-vcMMAE induced potent tumor cell killing against rituximab-sensitive and -resistant NHL cell lines. CD19 can form heterodimers with CD21, and high levels of CD21 were reported to interfere negatively with the activity of CD19-targeted therapeutics. However, we observed comparable internalization, intracellular trafficking, and drug release in CD21(low) and CD21(high), rituximab-sensitive and -refractory lymphomas treated with hBU12-vcMMAE. Furthermore, high rates of durable regressions in mice implanted with these tumors were observed, suggesting that both rituximab resistance and CD21 expression levels do not impact on the activity of hBU12-vcMMAE. Combined, our data suggest that hBU12-vcMMAE may represent a promising addition to the treatment options for rituximab refractory NHL and other hematologic malignancies, including acute lymphoblastic leukemia.
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PMID:Potent antitumor activity of the anti-CD19 auristatin antibody drug conjugate hBU12-vcMMAE against rituximab-sensitive and -resistant lymphomas. 1914 85

Mediastinal diffuse large B-cell lymphoma (Med-DLBCL) is a subtype of DLBCL that has morphologic and clinical similarities and phenotypic overlaps with classical Hodgkin lymphoma (CHL) involving the mediastinum. CD23 is a marker that has been previously reported in Med-DLBCI and is proposed in the differential diagnosis of M-DLBCL and CHL. A panel of immunostains, including CD45, CD20, CD3, CD30, CD15, CD21, and CD23 as well as Eber was performed on Med-DLBCL and 20CHL. 23/27 Med-DLBCL (85%) were positive for CD23 (membranous) CD30 was negative in 6 and positive in 21 cases. 18 CHL cases were negative for CD23 and only 2 showed rare scattered Reed-Sternberg cells with weak cytoplasmic CD23 staining. CD23 showed a sensitivity of 85% and positive predictive value of 92%. In conclusion CD23 is a useful marker in distinguishing Med-DLBCL and CHL in mediastinal biopsies and may be helpful as an adjunct to histomorphology and other markers in the diagnosis and appropriate clinical management of these lesions.
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PMID:The value of CD23 expression as an additional marker in distinguishing mediastinal (thymic) large B-cell lymphoma from Hodgkin lymphoma. 1922 73

Hepatitis C virus (HCV) is associated with the B-cell lymphoproliferative disorders mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. We have previously reported that HCV(+)MC(+) patients have clonal expansions of hypermutated, rheumatoid factor-bearing marginal zone-like IgM(+)CD27(+) peripheral B cells using the V(H)1-69 gene. Here we coupled transcriptional profiling with immunophenotypic and functional studies to ascertain these cells' role in MC pathogenesis. Despite their fundamental role in MC disease, these B cells have overall transcriptional features of anergy and apoptosis instead of neoplastic transformation. Highly up-regulated genes include SOX5, CD11C, galectin-1, and FGR, similar to a previously described FCRL4(+) memory B-cell subset and to an "exhausted," anergic CD21(low) memory B-cell subset in HIV(+) patients. Moreover, HCV(+)MC(+) patients' clonal peripheral B cells are enriched with CD21(low), CD11c(+), FCRL4(high), IL-4R(low) memory B cells. In contrast to the functional, rheumatoid factor-secreting CD27(+)CD21(high) subset, the CD27(+)CD21(low) subpopulation exhibits decreased calcium mobilization and does not efficiently differentiate into rheumatoid factor-secreting plasmablasts, suggesting that a large proportion of HCV(+)MC(+) patients' clonally expanded peripheral B cells is prone to anergy and/or apoptosis. Down-regulation of multiple activation pathways may represent a homeostatic mechanism attenuating otherwise uncontrolled stimulation of circulating HCV-containing immune complexes.
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PMID:Clonal B cells in patients with hepatitis C virus-associated mixed cryoglobulinemia contain an expanded anergic CD21low B-cell subset. 2194 Aug 29

Human Germinal Center-associated Lymphoma (HGAL) is a germinal center (GC) B-cell marker associated with a favorable outcome in diffuse large B-cell and classic Hodgkin lymphomas (CHL). To test its potential role in GC function, 75 cases involving GC disruption including 23 progressive transformation of germinal centers (PTGC), 25 follicle lysis and 27 Castleman disease (CD) were studied. HGAL protein expression uniformly correlated with GC B-cells in all except a subset of hyaline-vascular CD that showed severe regression of GCs. HGAL staining highlighted dismantled GCs in PTGC, in contrast to weak or absent CD10 and BCL6 staining. In follicle lysis, HGAL staining was comparable to that of CD10, BCL6, and CD21 in highlighting lysed follicles. Our findings show that HGAL protein expression effectively discriminates clusters of GC B-cells in disrupted follicles. Its persistence in disrupted GCs, suggests that it may be necessary for GC maintenance and supports its proposed role of confining B-cells to the GC microenvironment.
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PMID:HGAL protein expression persists in disorders of germinal center dissolution: potential role of HGAL in the germinal center microenvironment. 2147 40


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