Chanudet, E. et al. Chlamydia psittaci is variably associated with ocular adnexal MALT lymphoma in different geographical regions. J. Pathol. 209, 344-351

University of Cambridge, Cambridge, England, United Kingdom
The Journal of Pathology (Impact Factor: 7.43). 07/2006; 209(3):344-51. DOI: 10.1002/path.1984
Source: PubMed


Infectious agents play a critical role in MALT lymphoma development. Studies from Italy showed Chlamydia psittaci infection in 87% of ocular adnexal MALT lymphomas and complete or partial regression of the lymphoma after C. psittaci eradication in four of nine cases. However, C. psittaci was not demonstrated in ocular adnexal MALT lymphomas from the USA. This study was thus designed to investigate further the role of C. psittaci, and other infectious agents commonly associated with chronic eye disease, in the development of ocular adnexal MALT lymphoma. The presence of C. psittaci, C. trachomatis, C. pneumoniae, herpes simplex virus 1 and 2 (HSV1, HSV2), and adenovirus 8 and 19 (ADV8, ADV19) was assessed separately by polymerase chain reaction in 142 ocular adnexal MALT lymphomas, 53 non-marginal zone lymphomas, and 51 ocular adnexal biopsies without a lymphoproliferative disorder (LPD), from six geographical regions. C. psittaci was detected at similar low frequencies in non-LPD and non-marginal zone lymphoma groups from different geographical regions (0-14%). Overall, the prevalence of C. psittaci was significantly higher in MALT lymphomas (22%) than in non-LPD (10%, p=0.042) and non-marginal zone lymphoma cases (9%, p=0.033). However, the prevalence of C. psittaci infection in MALT lymphoma showed marked variation among the six geographical regions examined, being most frequent in Germany (47%), followed by the East Coast of the USA (35%) and the Netherlands (29%), but relatively low in Italy (13%), the UK (12%), and Southern China (11%). No significant differences in the detection of C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8, and ADV19 were found between lymphomas and controls from different geographical regions. In conclusion, our results show that C. psittaci, but not C. pneumoniae, C. trachomatis, HSV1, HSV2, ADV8 or ADV19, is associated with ocular adnexal MALT lymphoma and that this association is variable in different geographical areas.

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    • "It has been speculated that persistent C. psittaci infections (see Section 'Intracellular persistence') might play a key role in OAML development, which is supported by the fact that C. psittaci suppression via doxycycline is accompanied by detectable lymphoma regression (Ferreri et al., 2005). The prevalence of C. psittaci infection in MALT lymphomas seems to vary among regions (Chanudet et al., 2006 "
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    ABSTRACT: Chlamydia (C.) psittaci is an economically relevant pathogen in poultry and pet birds, where it causes psittacosis/ornithosis, and also a human pathogen causing atypical pneumonia after zoonotic transmission. Despite its well-documented prevalence, the agent has received less attention by researchers than other Chlamydia spp. in the last decades. In the present paper, we review recently published data on C. psittaci infection and attempt to single out characteristic features distinguishing it from related chlamydial agents. It is remarkable that C. psittaci is particularly efficient in disseminating in the host organism causing systemic disease, which occasionally can take a fulminant course. At the cellular level, the pathogen's broad host cell spectrum (from epithelial cells to macrophages), its rapid entry and fast replication, proficient use of intracellular transport routes to mitochondria and the Golgi apparatus, the pronounced physical association of chlamydial inclusions with energy-providing cell compartments, as well as the subversive regulation of host cell survival during productive and persistent states facilitate the characteristic efficient growth and successful host-to-host spread of C. psittaci. At the molecular level, the pathogen was shown to upregulate essential chlamydial genes when facing the host immune response. We hypothesize that this capacity, in concert with expression of specific effectors of the type III secretion system and efficient suppression of selected host defense signals, contributes to successful establishment of the infection in the host. Concerning the immunology of host-pathogen interactions, C. psittaci has been shown to distinguish itself by coping more efficiently than other chlamydiae with pro-inflammatory mediators during early host response, which can, to some extent, explain the effective evasion and adaptation strategies of this bacterium. We conclude that thorough analysis of the large number of whole-genome sequences already available will be essential to identify genetic markers of the species-specific features and trigger more in-depth studies in cellular and animal models to address such vital topics as treatment and vaccination. © FEMS 2014. All rights reserved. For permissions, please e-mail:
    Full-text · Article · Dec 2014 · Pathogens and Disease
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    • "In 2004, Ferreri et al. reported that they detected Cp DNA with targeted PCR in 80% of patients with ocular adnexal EMZL [9]. However, subsequent studies revealed that the prevalence of Cp infection in ocular adnexal EMZL cases varied among countries [4,10,11]. Regarding South Korea, a relatively high prevalence of Cp positivity (75–77%) has been repeatedly reported [12,13]. In addition, Cp-eradicating treatment using doxycycline antibiotics has been attempted as first-line targeted therapy in South Korea [4,13,14]. "
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    ABSTRACT: Purpose To compare genome-wide DNA methylation profiles according to Chlamydophila psittaci (Cp) infection status and the response to doxycycline treatment in Korean patients with ocular adnexal extranodal marginal zone B-cell lymphoma (EMZL). Methods Twelve ocular adnexal EMZL cases were classified into two groups (six Cp-positive cases and six Cp-negative cases). Among the 12 cases, eight were treated with doxycycline as first-line therapy, and they were divided into two groups according to their response to the treatment (four doxy-responders and four doxy-nonresponders). The differences in the DNA methylation states of 27,578 methylation sites in 14,000 genes were evaluated using Illumina bead assay technology. We also validated the top-ranking differentially methylated genes (DMGs) with bisulfite direct sequencing or pyrosequencing. Results The Infinium methylation chip assay revealed 180 DMGs in the Cp-positive group (74 hypermethylated genes and 106 hypomethylated genes) compared to the Cp-negative group. Among the 180 DMGs, DUSP22, which had two significantly hypomethylated loci, was validated, and the correlation was significant for one CpG site (Spearman coefficient=0.6478, p=0.0262). Regarding the response to doxycycline treatment, a total of 778 DMGs were revealed (389 hypermethylated genes and 336 hypomethylated genes in the doxy-responder group). In a subsequent replication study for representative hypomethylated (IRAK1) and hypermethylated (CXCL6) genes, the correlation between the bead chip analysis and pyrosequencing was significant (Spearman coefficient=0.8961 and 0.7619, respectively, p<0.05). Conclusions Ocular adnexal EMZL showed distinct methylation patterns according to Cp infection and the response to doxycycline treatment in this genome-wide methylation study. Among the candidate genes, DUSP22 has a methylation status that was likely attributable to Cp infection. Our data also suggest that the methylation statuses of IRAK1 and CXCL6 may reflect the response to doxycycline treatment.
    Full-text · Article · Jul 2014 · Molecular vision
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    • "In contrast, in another Italian series, Ferreri et al (2004) found evidence of C. psittaci in 32 of 40 (80%) cases of ocular adnexal MALT lymphomas. In studies analysing cases from the east coast of the USA, one found C. psittaci in 6 of 17 (35%) of ocular adnexal MALT lymphomas (Chanudet et al, 2006), whereas two other studies using the same methodology failed to demonstrate this bacterium in 7 and 46 cases, respectively (Rosado et al, 2006; Vargas et al, 2006). It is currently unknown, how much of these differences in series from the same region are due to case selection or technical factors. "
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    ABSTRACT: Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) comprises 7-8% of B-cell lymphomas and commonly originates from a background of long-standing chronic inflammation. An association with distinct bacteria species has been confirmed for several anatomical sites of MALT lymphoma. For pulmonary MALT lymphoma, however, a clear link with an infectious agent or autoimmune disorder has not yet been reported. Using a 16S rRNA gene-based approach, we have recently identified Achromobacter (Alcaligenes) xylosoxidans in eight of nine cases of pulmonary MALT lymphoma. A. xylosoxidans is a gram-negative betaproteobacterium with low virulence, but high resistance to antibiotic treatment. To further examine a potential association with A. xylosoxidans, 124 cases of pulmonary MALT lymphoma and 82 control tissues from six European countries were analysed using a specific nested PCR. Although prevalence rates for A. xylosoxidans varied significantly from country to country, they were consistently higher for MALT lymphoma as compared to controls. Overall, 57/124 (46%) pulmonary MALT lymphomas and 15/82 (18%) control tissues were positive for A. xylosoxidans (P = 0·004). Whether the significant association of A. xylosoxidans with pulmonary MALT lymphoma demonstrated in our study points to a potential causal role in the pathogenesis of this lymphoma will require further studies.
    Full-text · Article · Dec 2013 · British Journal of Haematology
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