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

Abstract

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.

Multigene Methylation Analysis of Ocular Adnexal MALT Lymphoma and Their Relationship toChlamydophila psittaciInfection and Clinical Characteristics in South Korea

“…Of these nine genes included in our study, only one gene (p16) has been previously reported to be methylated in ocular adnexal MALT lymphomas. 23 To the best of our knowledge, the other eight genes (p14, RASSF1A, MGMT, DAPK, THBS1, MT1G, RAR-b, and ECAD) we studied have not previously been investigated in detail in ocular adnexal MALT lymphomas. In this study, seven of nine genes (DAPK, ECAD, MT1G, THBS1, RAR-b, p16, and MGMT) showed methylation of CpG islands in the promoter region at frequencies of 5.7 to 94.3%, and all of the ocular adnexal MALT lymphoma cases had promoter hypermethylation in at least one of these genes.…”

“…23 In this study, we explored both the prevalence of aberrant methylation in a selected panel of nine TSGs that are known or rarely known to exist in lymphomas, using methylationspecific PCR, and the possible association with C. psittaci infection. The selected nine TSGs are known to be involved in cell cycle regulation (p14, p16, and RASSF1A), 24,25 DNA repair (MGMT), 26 apoptosis (DAPK [death-associated protein kinase] and RASSF1A), 27,28 angiogenesis inhibition (THBS1), 29 cell proliferation (MT1G and RAR-b), 25,30 and invasion suppression (ECAD [E-cadherin, CDH1]).…”

Review article: Mucosa-associated lymphoid tissue (MALT)-type lymphoma of ocular adnexa. Biology and treatment

“…However, other studies from Germany,USA, Netherlands, China, Cuba, Japan, France failed to show any association between Clamidia Psittaci and POAML (Rosado et al, 2005;Vargas et al, 2006;Zhang et al, 2007;Mulder et al, 2006;Daibata et al, 2006;. Therefore, it appears likely that there is a strong variability in the association of C. psittaci to POAMLs among different regions (Chanudet et al, 2006;Carugi et al, 2010;Husain et al, 2007).…”

“…In fact, it is well known that patients affected by POAML have high prevalence of Sjogren's syndrome, Hashimoto's thyroiditis and other autoimmune diseases, supporting the hypothesis that endoantigens could be the first trigger to the inflammatory cascade at the affected sites (Grünberger et al, 2008). POAML tissues in some studies have shown a high prevalence of infectious agents like Chlamydia psittaci, Chlamydia pneumoniae, Hepatitis C and Helicobacter pylori, supporting the hypothesis that exogenous antigens could also be the first trigger to the disease (Ferreri et al, 2004(Ferreri et al, , 2006aChanudet et al, 2006;Carugi et al, 2010;Luppi et al, 1996;Chan et al, 2006;Lee et al, 2008) as is the case in gastric MALT lymphoma.…”

Role of Chlamydia in the Development of Ocular Adnexal Lymphoma

“…have a prevalence below 10% [10,19,31,86,87]. In Kenya, where the underdeveloped conditions and the rather high plethora of infectious agents which could establish an excellent pabulum for the cancerous transformation and the development of the OAL, no association has been found between OAL and C. psittaci [88].…”