Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q06643 (non-Hodgkin's lymphoma)
 11,307 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Triggering of HLA class II antigens by the anti-HLA-DR monoclonal antibody (mAb) L243 significantly (P < 0.05) and differentially enhanced the release of tumor necrosis factor alpha (TNF-alpha) by the non-Hodgkin's lymphoma cells Ri-I, Ci-I, and Sc-I, which are at a distinct stage of B-cell differentiation, and by the more mature Burkitt lymphoma cell Raji; in contrast, it did not induce TNF-alpha release by the pre-B leukemia cells Nalm-6 and BV173. TNF-alpha release peaked at 24 h and decreased thereafter, and it was dose dependent and preceded by an increase of TNF-alpha mRNA detectable after 3 h of stimulation with mAb L243. Secreted TNF-alpha mediated the enhancement of nuclear factor kappa B (NF-kappa B) and activator protein-1 (AP-1) binding activity; in fact, the triggering of HLA-DR antigens in the presence of antihuman TNF-alpha-neutralizing antibodies did not upregulate NF-kappa B and AP-1. In contrast, released TNF-alpha was not responsible for the homotypic aggregation of Ri-I, Ci-I, Sc-I, and Raji cells induced by mAb L243, and it did not affect the proliferation of B cells investigated. Altogether, our data demonstrate that: (a) the ability of B cells to release TNF-alpha after triggering of HLA-DR antigens depends on their stage of differentiation; (b) levels of released TNF-alpha seem to correlate with the stage of B-cell maturation but do not correlate with the amounts of cell surface HLA-DR antigens; (c) secreted TNF-alpha regulates the levels of expression of NF-kappa B and AP-1 by an autocrine loop; and (d) intracellular signals mediating TNF-alpha release by B cells are distinct from those regulating homotypic aggregation and proliferation.
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PMID:Triggering of HLA-DR antigens differentially modulates tumor necrosis factor alpha release by B cells at distinct stage of maturation. 914 9

The distribution of HLA-DRB1 alleles and DQB1 alleles in 100 Thai patients with non-Hodgkin's lymphoma (NHL) was analysed using the polymerase chain reaction with sequence-specific primer (PCR-SSP) method, and the association between the disease and the presence of certain HLA class II alleles was investigated. The frequencies of HLA-DRB1*1502 and DRB1*09012 were increased while those of DRB1*0404, DRB1*0803 and DRB1*1106 were decreased. On the other hand, the incidence of HLA-DQB1 alleles was similar to that in the normal population. Interestingly, only HLA-DRB1*1502 showed a significant positive association with NHL, especially in patients < or / = 45 years and in male patients. It is concluded that the DRB1*1502 allele may contribute to NHL susceptibility in the Thai population. However, further studies on the functional roles of the HLA class II alleles are necessary to elucidate NHL susceptibility.
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PMID:HLA class II polymorphism in Thai patients with non-Hodgkin's lymphoma. 1058 59

The distribution of HLA-DRB1 alleles and DQB1 alleles in 30 Japanese patients with non-Hodgkin's lymphoma (NHL) was analyzed using polymerase chain reaction with the sequence-specific primer (PCR-SSP) method, and the association between the disease and the presence of certain HLA class II alleles was investigated. The frequencies of HLA-DRB1*0803, DRB1*0802 and DRB1*1502 were increased while those of DRB1*1501 and DRB1*0405 were decreased. On the other hand, the incidence of HLA-DQB1 alleles was similar to that in the normal population. However, none of these HLA class II alleles showed significant positive or negative associations with NHL. In addition, when allele frequencies of NHL Japanese patients were compared to Thai patients, only DRB1*0803 was significantly increased in Japanese patients. These results indicate that DRB1*0803 may not contribute to NHL susceptibility in the Japanese population. However, further studies with larger numbers of NHL Japanese patients are needed to confirm our preliminary findings.
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PMID:HLA class II alleles in Japanese patients with non-Hodgkin's lymphoma. 1128 20

Rituximab, a chimeric CD20 monoclonal antibody (mAb), is widely used in the treatment of patients with low-grade non-Hodgkin's lymphoma. Possible anti-tumour mechanisms involve complement-mediated lysis and/or antibody-dependent cellular cytotoxicity (ADCC). Because G-CSF greatly enhances the cytotoxicity of neutrophils (PMN) in ADCC, the clinical efficacy of rituximab might be enhanced by the addition of G-CSF. Therefore, we investigated the neutrophil-mediated CD20-dependent cellular cytotoxicity in B cell lines. In contrast to previous studies by others, we found that G-CSF-primed PMN are capable of functioning as effector cells in CD20-dependent cellular cytotoxicity. However, HLA class II mAbs were far more effective. The differences between HLA class II- and CD20-mediated PMN-ADCC were not due to: (1) the use of chimeric (hIgG1) mAbs vs mIgG2a mAbs; (2) HLA class II-induced apoptosis as an 'ADCC-sensitising' mechanism; (3) CD20-induced inhibition of ADCC; (4) inferior membrane mobility of CD20. Analysis of Fcgammareceptor (FcgammaR) involvement showed that although CD20-induced ADCC was mediated mainly via FcgammaRI, for optimal lysis FcgammaRI and FcgammaRII were both required. In contrast, in HLA class II-dependent ADCC both FcgammaRI and II were capable of independently inducing maximum lysis. The mechanism underlying these differences in FcgammaR-binding and activation remains to be elucidated.
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PMID:Analysis of CD20-dependent cellular cytotoxicity by G-CSF-stimulated neutrophils. 1196 Mar 51

Comparison of human leukocyte antigen (HLA) frequencies in patients with hepatitis C virus (HCV)-associated hepatocellular carcinoma (HCC) and in patients with HCV-associated non-Hodgkin's lymphoma (NHL) has not been addressed previously. To this aim, we investigated the distribution of HLA class II alleles in two selected groups of HCV-infected patients. Group 1 included 50 patients with HCV-associated NHL; group 2 included 29 patients with HCV-associated HCC. A control group included 144 hospitalized patients without NHL or HCC and who were negative for HCV, hepatitis B virus, and human immunodeficiency virus antibodies. Polymerase chain reaction sequence DRB1 and DQB1 specific-primer methods were used. DRB1*1101/DQB1*0301 haplotype, which mainly favors the spontaneous clearance of HCV infection, was lower in HCC subjects than in controls, whereas HLA-DRB1*1104/DQB1*0301, was higher in NHL patients. These findings suggest different pathogenic pathways in HCC and in NHL development. In patients with HCV-associated HCC, a major protective role of DQB1*0301 allele, rather than DRB1*11, was found, probably because of a better HLA class II-associated virus clearance. By contrast, the same allele as HLA-DRB1*04 showed an increase in HCV-associated NHL. These data suggest that NHL and HCC development may be associated to a different response with respect to chronic HLA class II-restricted antigen presentation (perhaps a switch toward CD4+Th2 response in NHL?) or, alternatively, that these alleles could be in linkage disequilibrium to unrelated gene(s), or are in synergy with other immunomodulatory genes that may confer increased risk for NHL.
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PMID:Hepatitis C virus-related hepatocellular carcinoma and B-cell lymphoma patients show a different profile of major histocompatibility complex class II alleles. 1555 90

Several risk factors including immune deficiencies, infections, and autoimmune diseases have been established for non-Hodgkin's lymphoma (NHL). For diffuse large B cell lymphoma (DLBCL), the most common type of lymphoma, no risk factors have been described, which may be due to the intrinsic heterogeneity of this disorder. Previously we reported that, in contrast to nodal DLBCLs, the majority of testicular DLBCLs manifested complete loss of HLA-DR and -DQ expression associated with homozygous deletions of the corresponding genes. To determine the correlation between HLA class II polymorphisms and these lymphomas, we applied DNA typing for HLA-DRB1 and HLA-DQB1 on 50 Dutch patients with testicular and 48 with nodal DLBCL and compared the frequencies with a cohort of healthy Dutch controls. Both the patients with nodal and those with testicular DLBCL manifested significantly higher frequencies of HLA-DRB1*15 than the controls (p < 0.018, odds ratio 2.09 and p < 0.013, odds ratio 2.12, respectively). Moreover, a positive association was seen with HLA-DRB1*12 (p = 0.043, odds ratio 4.17) in the patients with testicular DLBCL, and a negative association was seen with HLA-DRB1*07 (p = 0.022, odds ratio 0.13) in the patients with nodal DLBCL. Homozygous deletions of the HLA-DR/DQ region, evaluated by interphase fluorescence in situ hybridization were seen in 20 of 48 testicular tumors. No preferential loss or retention of a particular HLA-DR or -DQ allele was seen because all alleles were at least once retained or involved in a homozygous deletion.
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PMID:The relationship between HLA class II polymorphisms and somatic deletions in testicular B cell lymphomas of Dutch patients. 1672 Feb 10

Apolizumab is a humanized monoclonal antibody against a polymorphic epitope on HLA DRbeta that demonstrated evidence for therapeutic activity in follicular lymphoma patients. In pre-clinical studies, we previously reported that granulocyte colony-stimulating factor (G-CSF) treatment significantly enhanced lymphoma cell killing by HLA class II antibodies, including apolizumab. These results suggested a combination trial of apolizumab and G-CSF (filgrastim). In this trial, we treated six patients with relapsed or refractory 1D10-positive non-Hodgkin's lymphoma with filgrastim and variable doses of apolizumab ranging from 0.15 to 1.5 mg/m2. The combination was clinically well tolerated, with only two patients experiencing grade III/IV hematological toxicity (thrombocytopenia and autoimmune hemolytic anemia). Another patient developed a pruritic skin rash, which was probably a treatment-related grade II skin toxicity. Interestingly, two patients with follicular lymphoma who received intensified apolizumab treatment on a three times weekly schedule experienced prolonged stabilization of their disease for 12 and more than 36 months. In conclusion, this small pilot study suggests that a combination of HLA class II antibodies and G-CSF is clinically feasible.
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PMID:A humanized HLA-DR antibody (hu1D10, apolizumab) in combination with granulocyte colony-stimulating factor (filgrastim) for the treatment of non-Hodgkin's lymphoma: a pilot study. 1707 89

Several studies have been performed on the association between non-Hodgkin's lymphoma (NHL) and the presence of certain human leukocyte antigens (HLA) class II alleles in Asian countries, and these studies have shown different results, according to the ethnicity, for the frequencies of the HLA class II alleles, and especially for HLA-DRB1. Therefore, the distribution of the HLA-A, B, C, DRB1, and DQB1 alleles in 89 Korean patients with NHL and also in 200 healthy Korean controls was investigated in this study. For the class I alleles, the frequencies of HLA-B51 was increased in patients with NHL and diffuse large B cell (DLBC) lymphoma compared with the normal control. For the class II alleles, the frequencies of the HLA-DRB1*09 and DQB1*03 alleles were increased in patients with NHL and DLBC lymphoma compared with the normal controls. Also, the B51-DRB1*09-DQB1*03 haplotype was significantly increased in the patients with NHL. These results suggest that some genes in HLA-B*51-DRB1*09-DQB1*03 haplotype may contribute to NHL susceptibility in the Korean population.
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PMID:Association of HLA alleles with non-Hodgkin's lymphoma in Korean population. 1830 62

This investigation was focused on the contribution of individual human leukocyte antigen (HLA)-DR and -DQ alleles to the human hepatitis C virus (HCV)(+) non-Hodgkin's lymphoma (NHL), with and without mixed cryoglobulinemia (MC), to study whether individual HLA class II alleles are expressed preferentially or equally in human HCV-specific NHL. For this purpose, peripheral blood mononuclear cells were obtained from two groups of patients with HCV(+) NHL and with or without MC (70 and 71 cases, respectively), and from 4575 blood donors. Eighty-three subjects with HCV infection only, and 118 patients with MC, only without lymphoma, were added as additional control groups. Individual HLA-DR and -DQ alleles were determined using high-resolution sequence-based typing and then data were collected by considering the HLA-DRB1 and DQB1 supertypes on the basis of common structural and functional features, proposed by in silico Bioinformatic studies. From the data, it is evidenced that the DR5-DQ3 HLA combination was strongly associated with the HCV (+) MC (+) NHL group of patients compared with bone marrow donor population (P<or= 0.001, RR = 2.498), while the contribution of DR1-DQ1 was higher in HCV (+) NHL without MC (P<or= 0.001, RR = 2.519). Thus, cryoglobulinemia clinical manifestation was found to be correlated with the preferential use of HLA DR-DQ combination in HCV-associated NHL. These data provide new insight into HCV-associated lymphoproliferative pathogenesis.
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PMID:HLA DR-DQ combination associated with the increased risk of developing human HCV positive non-Hodgkin's lymphoma is related to the type II mixed cryoglobulinemia. 2000 9