title: 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.
authors.affiliation: Department Human Pathology and Oncology, University of Siena, 53100 Siena, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Carugi
authors.forename: Anna
authors.initials: A
authors.lastname: Onnis
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Antonicelli
authors.forename: Benedetta
authors.initials: B
authors.lastname: Rossi
authors.forename: Susanna
authors.initials: S
authors.lastname: Mannucci
authors.forename: Anna
authors.initials: A
authors.lastname: Luzzi
authors.forename: Stefano
authors.initials: S
authors.lastname: Lazzi
authors.forename: Cristiana
authors.initials: C
authors.lastname: Bellan
authors.forename: Gian Marco
authors.initials: GM
authors.lastname: Tosi
authors.forename: Shaheen
authors.initials: S
authors.lastname: Sayed
authors.forename: Giulia
authors.initials: G
authors.lastname: De Falco
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002691:Chlamydophila psittaci / Q000235:genetics* / Q000302:isolation & purification*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D004269:DNA, Bacterial / Q000032:analysis; D015536:Down-Regulation; D024202:Electrophoretic Mobility Shift Assay; D015818:Eye Infections, Bacterial / Q000382:microbiology*; D005134:Eye Neoplasms / Q000382:microbiology*; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D007558:Italy; D007630:Kenya; D018442:Lymphoma, B-Cell, Marginal Zone / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D009956:Psittacosis / Q000382:microbiology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D004269:DNA, Bacterial