Molecular and genomic aberrations in <i>Chlamydophila psittaci</i> negative ocular adnexal marginal zone lymphomas

Zhu, Daxing; Ikpatt, Offiong Francis; Dubovy, Sander R.; Lossos, Chen; Natkunam, Yasodha; Chapman-Fredricks, Jennifer R.; Fan, Yao Shan; Lossos, Izidore S.

doi:10.1002/ajh.23490

Cited by 33 publications

(28 citation statements)

References 43 publications

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“…6,7 Although the pathogenesis of MALT lymphomas in these anatomic locations has been extensively studied, 8,9 the pathogenesis and etiology of ocular adnexal EMZLs (OAEMZLs), the second most common EMZL and the most common tumor occurring in the ocular adnexa, are still controversial. 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.…”

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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“…It most frequently infects Psittaciformes but can also infect many other avian species, as well as a wide range of mammalian hosts (Kaleta and Taday, 2003;Zhu et al, 2013). The highest infection rates are identified in psittacine birds and pigeons (Donham and Zejda, 1992;Pilny et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Prevalence and genotype of Chlamydia psittaci in faecal samples of birds from zoos and pet markets in Kunming, Yunnan, China

Feng

Zhang

et al. 2016

J. Zhejiang Univ. Sci. B

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Abstract:Chlamydia psittaci is an important zoonotic pathogen in birds and may be transmitted to humans and result in severe respiratory disease. To assess the prevalence and genotype of C. psittaci in birds in Kunming, Yunnan, China, a total of 136 specimens of psittacine birds involving 8 species were collected from the city's zoos (n=60) and pet markets (n=76). The frequency of C. psittaci infection was 19.9% (27/136) in the psittacine birds. The prevalence of C. psittaci was higher in pet birds (26.3%; 20/76) than in zoo birds (11.7%; 7/60) (P=0.034). In particular, among Agapornis fischeri, the C. psittaci infection (50%; 10/20) was significantly more frequent in the pet markets than in the zoos (P=0.006). In addition, the highest prevalence of 41.2% (7/17) was found in Ara ararauna. To determine the genotype of C. psittaci, 23 OmpA gene fragments (about 1.4 kb) in 27 positive samples were successfully amplified and sequenced. Phylogenetic analysis showed that all the 23 strains belonged to genotype A. Our results demonstrate the high prevalence of C. psittaci genotype A infection in psittacine birds in Yunnan Province, suggesting a potential threat to human health in this area. Therefore, it is necessary to take effective measures to prevent the spread of C. psittaci among psittacine birds, as well as among employees and customers.

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“…9 The pathogenesis of these tumors was elucidated by an investigation of the prevalence of chromosomal translocations and mutations, which showed alterations in genes that regulate cell survival and apoptosis pathways, as well as through interrogation of immunoglobulin gene usage and analysis of somatic mutations. [9][10][11] These studies implicated a role for autoantigen-induced activation of the B-cell receptor in the pathogenesis of POAML. 12 While major advances were achieved, a large gap in knowledge of POAML exists, primarily due to the rarity of this disease.…”

Section: Introductionmentioning

confidence: 99%

Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

Desai

Joag

Lekakis

et al. 2017

Blood

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Key Points• POAML (specifically Ann Arbor stage I disease) has an excellent clinical outcome, with only a few patients succumbing to lymphoma.• POAML patients face a continuous risk of distant relapse, including in the central nervous system, and transformation to aggressive lymphoma.While primary ocular adnexal mucosa-associated lymphoid tissue (MALT) lymphoma (POAML) is the most common orbital tumor, there are large gaps in knowledge of its natural history. We conducted a retrospective analysis of the largest reported cohort, consisting of 182 patients with POAML, diagnosed or treated at our institution to analyze long-term outcome, response to treatment, and incidence and localization of relapse and transformation. The majority of patients (80%) presented with stage I disease. Overall, 84% of treated patients achieved a complete response after first-line therapy. In patients with stage I disease treated with radiation therapy (RT), doses ‡30.6 Gy were associated with a significantly better complete response rate (P 5 .04) and progression-free survival (PFS) at 5 and 10 years (P < .0001). Median overall survival and PFS for all patients were 250 months (95% confidence interval [CI], 222 [upper limit not reached]) and 134 months (95% CI, 87-198), respectively. Kaplan-Meier estimates for the PFS at 1, 5, and 10 years were 91.5% (95% CI, 86.1% to 94.9%), 68.5% (95% CI, 60.4% to 75.6%), and 50.9% (95% CI, 40.5% to 61.6%), respectively. In univariate analysis, age >60 years, radiation dose, bilateral ocular involvement at presentation, and advanced stage were significantly correlated with shorter PFS (P 5 .006, P 5 .0001, P 5 .002, and P 5 .0001, respectively). Multivariate analysis showed that age >60 years (hazard ratio [HR] 2.44) and RT<30.6Gy (HR54.17) were the only factors correlated with shorter PFS (P 5 .01 and P 5 .0003, respectively). We demonstrate that POAMLs harbor a persistent and ongoing risk of relapse, including in the central nervous system, and transformation to aggressive lymphoma (4%), requiring long-term follow-up. (Blood. 2017;129(3):324-332)

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Molecular and genomic aberrations in Chlamydophila psittaci negative ocular adnexal marginal zone lymphomas

Cited by 33 publications

References 43 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

Prevalence and genotype of Chlamydia psittaci in faecal samples of birds from zoos and pet markets in Kunming, Yunnan, China

Long-term course of patients with primary ocular adnexal MALT lymphoma: a large single-institution cohort study

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