Variable association between Chlamydophila psittaci infection and ocular adnexal lymphomas: methodological biases or true geographical variations?

Decaudin, Didier; Dolcetti, Riccardo; Crémoux, Patricia de; Ponzoni, Maurilio; Vincent‐Salomon, Anne; Doglioni, Claudio; Dendale, R.; Escande, Marie; Rouic, Livia Lumbroso‐Le; Ferreri, Andrés J.M.

doi:10.1097/cad.0b013e32830b58c4

Cited by 39 publications

(26 citation statements)

References 32 publications

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“…1,[10][11][12] Chlamydophila psittaci infection was implicated in the pathogenesis of OAEMZLs, but this association demonstrated marked differences based on geography. 1,13,14 Most studies originating from North American institutions did not detect C. psittaci in OAEMZL tumors. 13,15,16 Further, we have previously reported that C. psittaci-negative OAEMZLs usually do not harbor the classical chromosomal translocations t(14;18)(q32;q21) IGH-MALT1 and t(11;18)(q21;q21) API2-MALT1 implicated in the pathogenesis of EMZLs originating in other anatomical locations.…”

Section: Introductionmentioning

confidence: 96%

Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors

Zhu

Bhatt

et al. 2015

Leukemia

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The pathogenesis of Chlamydophila psittaci-negative ocular adnexal extranodal marginal zone lymphomas (OAEMZLs) is poorly understood. OAEMZLs are monoclonal tumors expressing a biased repertoire of mutated surface immunoglobulins. Antigenic activation of the B-cell receptor (BCR) may have a role in the pathogenesis of these lymphomas. We have analyzed the reactivity of recombinant OAEMZL immunoglobulins. OAEMZL antibodies reacted with self-human antigens, as demonstrated by enzyme-linked immunosorbent assays, HEp-2 immunofluorescence and human protein microarrays. All the analyzed recombinant antibodies (rAbs) exhibited polyreactivity by comprehensive protein array antibody reactivity and some rAbs also demonstrated rheumatoid factor activity. The identity of several reactive antigens was confirmed by microcapillary reverse-phase high-performance liquid chromatography nano-electrospray tandem mass spectrometry. The tested rAbs frequently reacted with shared intracellular and extracellular self-antigens (for example, galectin-3). Furthermore, these self-antigens induced BCR signaling in B cells expressing cognate surface immunoglobulins derived from OAEMZLs. These findings indicate that interactions between self-antigens and cognate OAEMZL tumor-derived BCRs are functional, inducing intracellular signaling. Overall, our findings suggest that self-antigen-induced BCR stimulation may be implicated in the pathogenesis of C. psittaci-negative OAEMZLs.

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Section: Introductionmentioning

confidence: 96%

Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors

Zhu

Bhatt

et al. 2015

Leukemia

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“…In a prospective case-controlled study from Italy, a significant association was demonstrated between exposure to household animals, rural residence, and history of chronic conjunctivitis in patients with OAEMZLs [8]. Furthermore, the Italian group and investigators from several other geographic regions demonstrated Chlamydophila psittaci (C. psittaci ) DNA and bacteria present in OAEMZLs [7], [8], [9], [10], [11], [12], suggesting that this pathogen may be implicated in the development of these lymphomas analogously to Helicobacter pylori in gastric EMZLs. However, similar studies performed by us and other investigators on US and non-US-based patients have failed to corroborate the finding of C. psittaci in OAEMZLs, potentially suggesting geographic differences [7], [13], [14], [15], [16].…”

Section: Introductionmentioning

confidence: 99%

Biased Use of the IGHV4 Family and Evidence for Antigen Selection in Chlamydophila psittaci-Negative Ocular Adnexal Extranodal Marginal Zone Lymphomas

et al. 2011

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Extranodal marginal zone lymphomas (EMZL) are the most common lymphomas in the ocular adnexa. The etiology and potential role for antigenic stimulation in these lymphomas are still controversial. We have examined IGHV gene usage and mutations in 67 Chlamydophila psittaci-negative ocular adnexal EMZL. Clonal IGHV gene sequences were identified in 43 tumors originating from the orbit (19), conjunctivae (18) and lacrimal gland (6). Forty four potentially functional clonal IGHV gene sequences were detected with overrepresentation of the IGHV4 family and IGHV4-34 gene. All but 3 sequences were mutated with the average percent homology to the germ line of 93.5±6.1. Multinomial model and Focused binomial test demonstrated evidence for positive and/or negative antigen selection in 59% of the potentially functional IGHV genes. Intraclonal variation was detected in 8 of 11 tumor specimens. Overall our findings demonstrate that C. psittaci-negative ocular adnexal EMZL exhibit biased usage of IGHV families and genes with evidence for intraclonal heterogeneity and antigen selection in multiple tumors, implicating B-cell receptor-mediated antigen stimulation in the pathogenesis of these lymphomas.

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“…In fact, the frequencies of Chlamydia psittasi positive ocular adnexal extranodal marginal zone lymphomas have a large variability across geographical regions and even between series from the same geographical regions (Collina et al 2012). Therefore, it has been questioned whether this variable association between Chlamydia psittasi and ocular adnexal extranodal marginal zone lymphoma reflects methodological biases or true geographical variation (Decaudin et al 2008). Although the exact role of Chlamydia psittasi in lymphomagenesis remains to be elucidated, doxycycline seems to be an alternative treatment modality in Chlamydia psittasi positive ocular adnexal lymphomas.…”

Section: Treatmentmentioning

confidence: 99%

Diffuse large B‐cell lymphoma and mantle cell lymphoma of the ocular adnexal region, and lymphoma of the lacrimal gland: An investigation of clinical and histopathological features

Rasmussen

2013

Acta Ophthalmologica

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Diffuse large B‐cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) constitute two distinct subtypes of non‐Hodgkin lymphoma (NHL) associated with considerable morbidity and mortality.Marked diversities with regard to molecular biology and clinical features are recognized in different subsets of the two lymphomas. Because these differences could be related to the location of the lymphoma, it is of interest to investigate the clinical and histopathological features of DLBCL and MCL involving the ocular adnexal region (i.e. the orbit, eyelids, conjunctiva, lacrimal gland and lacrimal sac). Similarly, the lacrimal gland is the only glandular structure within the orbit. Because the lacrimal gland represents an important part of the immunological system, it is of interest to investigate lymphomas involving this location with regard to clinical and histological characteristics.Purpose: To characterize the clinical and histopathological features of Danish patients with DLBCL of the ocular adnexal region between 1980 and 2009 and of Danish ocular adnexal MCL patients from 1980 to 2005. Furthermore, the aim of this PhD was to review all specimens from patients with lymphoma of the lacrimal gland in Denmark between 1975 and 2009 to determine the distribution of lymphoma subtypes of the lacrimal gland and to describe the clinicopathological features of these patients.Results: A total of 34 patients with DLBCL and 21 with MCL of the ocular adnexal region were identified. Twenty‐seven patients had lacrimal gland lymphoma, including four DLBCLs and three MCLs from studies I and II.Elderly patients predominated in all three groups, with median ages of 78, 75 and 69 years in the DLBCL, the MCL and the lacrimal gland lymphoma groups, respectively. MCL patients had a preponderance of males, whereas females prevailed among lacrimal gland lymphoma patients. The orbit was the most common site of involvement in DLBCL and MCL. Most DLBCL patients had unilateral involvement, while MCL patients had a high frequency of bilateral involvement. Similarly, localized lymphoma was relatively frequently seen in DLBCL patients in contrast to the predominance of disseminated lymphoma in the MCL group.The majority of lacrimal gland lymphomas were low grade, and the distribution of subtypes was as follows: extranodal marginal zone lymphoma, 10 (37%); follicular lymphoma, 5 (19%); DLBCL, 4 (15%); MCL, 3 (11%); chronic lymphocytic leukaemia/small lymphatic lymphoma, 2 (7%); and unclassified B‐cell lymphoma, 3 (11%).The overall survival rates at 3 and 5 years for the entire study group of DLBCL were 42% and 20%, whereas 58% and 22% of MCL patients were alive 3 and 5 years after the time of diagnosis. The 5‐year overall survival rate of lacrimal gland lymphoma patients was 70%.Concordant bone marrow involvement and the International Prognostic Index score were predictive factors for the overall survival in the DLBCL group in Cox regression analysis. Rituximab‐containing chemotherapy was associated with an improved survival rate in MCL patients.Conclusions: Diffuse large B‐cell lymphoma and MCL involving the ocular adnexal region and lymphoma of the lacrimal gland are prevalent among elderly patients. The overall prognosis in DLBCL and MCL was poor, whereas the prognosis for lacrimal gland lymphoma patients was relatively good. Concordant bone marrow involvement and the International Prognostic Index score were independent predictive factors for mortality in the DLBCL group. Chemotherapy containing rituximab significantly improved survival in the MCL group.

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Variable association between Chlamydophila psittaci infection and ocular adnexal lymphomas: methodological biases or true geographical variations?

Cited by 39 publications

References 32 publications

Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors

Chlamydophila psittaci-negative ocular adnexal marginal zone lymphomas express self polyreactive B-cell receptors

Biased Use of the IGHV4 Family and Evidence for Antigen Selection in Chlamydophila psittaci-Negative Ocular Adnexal Extranodal Marginal Zone Lymphomas

Diffuse large B‐cell lymphoma and mantle cell lymphoma of the ocular adnexal region, and lymphoma of the lacrimal gland: An investigation of clinical and histopathological features

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