Background: Ocular adnexal lymphomas may be antigen-driven disorders; however, the source of the putative antigen or antigens is still unknown. Hence, we assessed whether Chlamydiae infection is associated with the development of ocular adnexal lymphomas. Methods: The presence of Chlamydia psittaci, trachomatis, and pneumoniae DNA was investigated by polymerase chain reaction in 40 ocular adnexal lymphoma samples, 20 nonneoplastic orbital biopsies, 26 reactive lymphadenopathy samples, and peripheral blood mononuclear cells (PBMCs) from 21 lymphoma patients and 38 healthy individuals. Seven patients with chlamydia-positive PBMCs were treated with the antibiotic doxycycline, and objective response was assessed in four patients with measurable lymphoma lesions. Differences in Chlamydiae DNA detection between the case patients and the control subjects were analyzed using the Fisher exact test. All statistical tests were two-sided. Results: Thirty-two of the 40 (80%) ocular adnexal lymphoma samples carried C. psittaci DNA, whereas all lymphoma samples were negative for C. trachomatis and C. pneumoniae. In contrast, none of the 20 nonneoplastic orbital biopsies (0% versus 80%; P<.001) and only three of 26 (12%) reactive lymphadenopathy samples (12% versus 80%; P<.001) carried the C. psittaci DNA. Nine of 21 (43%) patients with chlamydia-positive lymphomas carried C. psittaci DNA in their PBMCs, whereas none (0%) of the healthy PBMC donors carried C. psittaci DNA in their PBMCs (43% versus 0%; P<.001). One month after doxycycline treatment, chlamydial DNA was no longer detectable in the PBMCs of all seven treated patients, and objective response was observed in two of the four evaluable patients. Conclusion: Patients with ocular adnexal lymphoma had a high prevalence of C. psittaci infection in both tumor tissue and PBMCs. Persistent C. psittaci infection may contribute to the development of these lymphomas, as was also supported by the clinical responses observed in this study with C. psittaci–eradicating antibiotic therapy.

Healthy lifestyles are associated with better health-related quality of life (HRQoL), favorable prognosis and lower mortality in breast cancer (BC) survivors. We investigated changes in HRQoL after a 12-month lifestyle modification program in 227 BC survivors participating in DEDiCa trial (Mediterranean diet, exercise, vitamin D). HRQoL was evaluated through validated questionnaires: EQ-5D-3L, EORTC-QLQ-C30 and EORTC QLQ-BR23. Baseline changes were tested using analysis of variance. Multiple regression analyses were performed to assess treatment effects on HRQoL. Increases were observed in global health status (p < 0.001), physical (p = 0.003), role (p = 0.002) and social functioning (p < 0.001), body image (p < 0.001), future perspective (p < 0.001), well-being (p = 0.001), and reductions in fatigue (p < 0.001), nausea and vomiting (p = 0.015), dyspnea (p = 0.001), constipation (p = 0.049), financial problems (p = 0.012), sexual functioning (p = 0.025), systematic therapy side effects (p < 0.001) and breast symptoms (p = 0.004). Multiple regression analyses found inverse associations between changes in BMI and global health status (p = 0.048) and between serum 25(OH)D levels and breast symptoms (p = 0.002). A healthy lifestyle treatment of traditional Mediterranean diet and exercise may impact positively on HRQoL in BC survivors possibly through reductions in body weight while vitamin D sufficiency may improve BC-related symptoms. These findings are relevant to BC survivors whose lower HRQoL negatively affects treatment compliance and disease outcomes.

The variability in the association of host innate immune response to Hepatitis C virus (HCV) infection requires ruling out the possible role of host KIR and HLA genotypes in HCV-related disorders: therefore, we therefore explored the relationships between KIR/HLA genotypes and chronic HCV infection (CHC) as they relate to the risk of HCV-related hepatocarcinoma (HCC) or lymphoproliferative disease progression. We analyzed data from 396 HCV-positive patients with CHC (n = 125), HCC (118), and lymphoproliferative diseases (153), and 501 HCV-negative patients. All were HIV and HBV negative. KIR-SSO was used to determine the KIR typing. KIR2DL5 and KIR2DS4 variants were performed using PCR and GeneScan analysis. HLA/class-I genotyping was performed using PCR-sequence-based typing. The interaction between the KIR gene and ligand HLA molecules was investigated. Differences in frequencies were estimated using Fisher’s exact test, and Cochran-Armitage trend test. The non-random association of KIR alleles was estimated using the linkage disequilibrium test. We found an association of KIR2DS2/KIR2DL2 genes, with the HCV-related lymphoproliferative disorders. Furthermore, individuals with a HLA-Bw6 KIR3DL1+ combination of genes showed higher risk of developing lymphoma than cryoglobulinemia. KIR2DS3 gene was found to be the principal gene associated with chronic HCV infection, while a reduction of HLA-Bw4 + KIR3DS1+ was associated with an increased risk of developing HCC. Our data highlight a role of the innate-system in developing HCV-related disorders and specifically KIR2DS3 and KIR2D genes demonstrated an ability to direct HCV disease progression, and mainly towards lymphoproliferative disorders. Moreover the determination of KIR3D/HLA combination of genes direct the HCV progression towards a lymphoma rather than an hepatic disease. In this contest IFN-α therapy, a standard therapy for HCV-infection and lymphoproliferative diseases, known to be able to transiently enhance the cytotoxicity of NK-cells support the role of NK cells to counterstain HCV-related and lymphoproliferative diseases.

Background & Aims T cells are an important component for development of a vaccine against hepatitis C virus (HCV), but little is known about the features of successful vaccine-induced T cells. Methods We compared the phenotype, function, and kinetics of vaccine-induced and infection-induced T cells in chimpanzees with HCV infection using multicolor flow cytometry and real-time polymerase chain reaction. Results In chimpanzees successfully vaccinated with recombinant adenovirus and DNA against HCV NS3-5, HCV-specific T cells appeared earlier, maintained better functionality, and persisted at higher frequencies for a longer time after HCV challenge, than those of mock-vaccinated chimpanzees. Vaccine-induced T cells displayed higher levels of CD127, a marker of memory precursors, and lower levels of programmed death-1 (PD-1) than infection-induced T cells. Vaccine-induced, but not infection-induced, T cells were multifunctional; their ability to secrete interferon gamma and tumor necrosis factor α correlated with early expression of CD127 but not PD-1. Based on a comparison of vaccine-induced and infection-induced T cells from the same chimpanzee, the CD127⁺ memory precursor phenotype was induced by the vaccine itself rather than by low viremia. In contrast, induction of PD-1 correlated with viremia, and levels of intrahepatic PD-1, PD-L1, and 2,5-OAS-1 messenger RNAs correlated with peak titers of HCV. Conclusions Compared with infection, vaccination-induced HCV-specific CD127⁺ T cells with high functionality that persisted at higher levels for a longer time. Control of viremia prevented up-regulation of PD-1 on T cells and induction of PD-1, PD-L1, and 2,5-OAS-1 in the liver. Early development of a memory T-cell phenotype and, via control of viremia, attenuation of the inhibitory PD1–PD–L1 pathway might be necessary components of successful vaccine-induced protection against HCV.

We demonstrate that in three cases of MC (two with immunocytoma), the IgM-RF+ component of their cryoprecipitated represents the circulating counterpart of the B-cell receptor (BCR) of the monoclonal overexpanded B-cell population. These IgMs were isolated and used to demonstrate a crossreactivity against both hepatitis C virus (HCV) NS3 antigen and the Fc portion of IgG. Epitopes were identified in a fraction of exemplary samples by using epitope excision approach (NS_31250–1334 and IgG Fc_345–355). The same phenomenon of crossreactivity has been shown to occur in vivo after immunization of a mouse with the NS3_1251−1270 peptide. To verify if the same reaction was also present in MC samples characterized by an oligo/polyclonal B-cell proliferation, IgM crossreactivity was tested in 14 additional samples. Five out of the 14 were reactive against HCV NS3 and 11 out of 14 were reactive against IgG-Fc peptide. The data support the role of HCV NS3 antigen in a subset of patients with MC, whereas the high frequency of the IgG-Fc epitope suggests that these B cells originate from precursors strongly selected for auto-IgG specificity. We suggest that engagement of specific BCRs by NS3 (or NS3-immunocomplex) antigen could explain the prevalence of IgM cryoglobulins in these patients