Ocular adnexal lymphoma: no evidence for bacterial DNA associated with lymphoma pathogenesis

Matthews, Julie Marie; Moreno, Lilliana I.; Dennis, Jeremy; Byrne, Gerald E.; Ruiz, Phillip; Dubovy, Sander R.

doi:10.1111/j.1365-2141.2008.07112.x

Cited by 33 publications

(17 citation statements)

References 16 publications

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“…9 Notwithstanding these achievements, the precise mechanisms of antigenic stimulation are not yet fully elucidated and could theoretically evoke a direct role of still unidentified bacterial Ags and/or the indirect triggering by unrelated antigenic element(s) exposed within the context of the tissue inflammation. 34 In the present study, the predominant usage of IGHV3 subgroup genes (78.3%) and, mostly, the preferential usage of four IGHV genes, accounting for almost half of cases, allude to selection of IGHV specificities by antigenic exposure. 2,[11][12][13][14] Previous studies on more limited series 2,[11][12][13][14] indicated that the IGHV3-23 and IGHV3-7 genes were the predominant IGHV genes in ocular adnexal lymphomas, albeit their overall combined frequency was rather low (10.6% in total).…”

Section: Discussionmentioning

confidence: 50%

Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation

et al. 2011

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Evidence from certain geographical areas links lymphomas of the ocular adnexa marginal zone B-cell lymphomas (OAMZL) with Chlamydophila psittaci (Cp) infection, suggesting that lymphoma development is dependent upon chronic stimulation by persistent infections. Notwithstanding that, the actual immunopathogenetical mechanisms have not yet been elucidated. As in other B-cell lymphomas, insight into this issue, especially with regard to potential selecting ligands, could be provided by analysis of the immunoglobulin (IG) receptors of the malignant clones. To this end, we studied the molecular features of IGs in 44 patients with OAMZL (40% Cp-positive), identifying features suggestive of a pathogenic mechanism of autoreactivity. Herein, we show that lymphoma cells express a distinctive IG repertoire, with electropositive antigen (Ag)-binding sites, reminiscent of autoantibodies (auto-Abs) recognizing DNA. Additionally, five (11%) cases of OAMZL expressed IGs homologous with autoreactive Abs or IGs of patients with chronic lymphocytic leukemia, a disease known for the expression of autoreactive IGs by neoplastic cells. In contrast, no similarity with known anti-Chlamydophila Abs was found. Taken together, these results strongly indicate that OAMZL may originate from B cells selected for their capability to bind Ags and, in particular, auto-Ags. In OAMZL associated with Cp infection, the pathogen likely acts indirectly on the malignant B cells, promoting the development of an inflammatory milieu, where auto-Ags could be exposed and presented, driving proliferation and expansion of self-reactive B cells.

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Section: Discussionmentioning

confidence: 50%

Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation

et al. 2011

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“…At our institution, analysis of 49 OAML samples using 2 distinct PCR techniques based on universal bacterial primers failed to detect bacterial DNA in any of the cases. 44 Overall, the studies published to date suggest variable associations between Cp and OAML across geographic regions worldwide. However, differences in PCR methodology may also contribute to some of the differences observed in these studies.…”

Section: Association With C Psittaci Infectionmentioning

confidence: 99%

Extranodal marginal zone lymphoma of the ocular adnexa

Stefanovic

Lossos

2009

Blood

Self Cite

199

214

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“…Different studies have reported the possible role of C. psittaci in the development of OAL, ranging from its association in 87% of the cases in a cohort of Italian patients, to no association, as reported by studies from the US, Netherland, Japan [20][21][22]36]; these findings suggest that there is a geographic variability for C. psittaci association and that other aetiological factors may be involved in the development of this lymphoma.…”

Section: Discussionmentioning

confidence: 74%

Geographic variation and environmental conditions as cofactors in Chlamydia psittaci association with ocular adnexal lymphomas: a comparison between Italian and African samples

Carugi

Onnis

Antonicelli

et al. 2009

Hematological Oncology

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A particular extra-nodal lymphoma type arises from B cells of the marginal zone (MZ) of mucosa-associated lymphoid tissue (MALT). The aetiology of MZ lymphomas suggests that they are associated with chronic antigenic stimulation by microbial pathogens, among which Helicobacter pylori-associated gastric MALT lymphoma is the best studied. Recently, MALT lymphomas have been described in the context of chronic conjunctivitis, which can be associated with Chlamydia spp. infection. Studies from Italy showed the presence of Chlamydia psittaci in 87% of ocular adnexal lymphomas (OAL), and C. psittaci has been described in a large part of samples from Austria and Korea as well. However, this finding was not always confirmed by other studies, suggesting that the association with C. psittaci may depend on geographic heterogeneity. Interestingly, none of the studies up to now has been carried out in the African population, where a strong association between infectious agents and the occurrence of human neoplasms has been reported. This study was designed to investigate the possible association of Chlamydia psittaci in cases retrieved from Kenya, compared to cases from Italy. Our results showed that there was a marked variation between the two geographical areas in terms of association with C. psittaci, as 17% (5/30) of the samples from Italy were positive for C. psittaci, whereas no association with this pathogen was observed in any of the African samples (0/9), suggesting that other cofactors may determine the OAL occurrence in those areas. OAL cases are often characterized by down-regulation of p16/INK4a expression and promoter hypermethylation of the p16/INK4a gene. Our results showed a partial methylation of p16/INK4a promoter in C. psittaci-negative cases, whereas no hypermethylation of this gene was found in C. psittaci-positive cases, suggesting that mechanisms other than promoter hypermethylation lead to p16/INK4a silencing in C. psittaci-positive cases. We may conclude that the role of epidemiologic, environmental and genetic factors, must be considered in the aetiology of this disease.

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Ocular adnexal lymphoma: no evidence for bacterial DNA associated with lymphoma pathogenesis

Cited by 33 publications

References 16 publications

Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation

Immunoglobulin gene repertoire in ocular adnexal lymphomas: hints on the nature of the antigenic stimulation

Extranodal marginal zone lymphoma of the ocular adnexa

Geographic variation and environmental conditions as cofactors in Chlamydia psittaci association with ocular adnexal lymphomas: a comparison between Italian and African samples

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