Killer (FASL regulatory) B cells are present during latent TB and are induced by BCG stimulation in participants with and without latent tuberculosis.

Regulatory B cells (Bregs) have been shown to be present during several disease states. The phenotype of the cells is not completely defined and the function of these cells differ between disease. The presence of FASL expressing (killer) B cells during latent and successfully treated TB disease have been shown but whether these cells are similar to regulatory B cells remain unclear. We assessed the receptor expression of FASL/IL5 (killer B cells), CD24/CD38 (regulatory B cells) on whole peripheral blood of participants with untreated active TB and healthy controls. We then isolated B cells from a second cohort of M.tb exposed (Quantiferon (QFN) positive) and unexposed (Quantiferon negative) HIV negative participants, and evaluated the frequency of killer B cells induced following stimulation with BCG and/or CD40 and IL5. Our data reveal no difference in the expression on CD24 and CD38 between participants with active TB and the controls. There was also no difference in the frequency of regulatory B cells measured in the peripheral blood mononuclear cells (PBMC) fraction between latent TB and uninfected controls. We did however notice that regulatory B cells (CD24hiCD38hi) population express the FASL receptor. The expression of killer B cell phenotype (CD178+IL5RA+) was significantly higher in controls compared to those with active TB disease (1,06% vs 0,455%). Furthermore, we found that BCG restimulation significantly induced the FASL/IL5RA B cells but this was only evident in the QFN positive group. Our data suggest that both regulatory and killer B cells are present during latent and active TB disease but that the frequency of these populations are increased during latent disease. We also show that the FASL+IL5RA+ B killer B cells are induced in latent TB infection following BCG restimulation but whether these cells are indicative of protection remains unclear.

Value of Diaphragmatic Surgery During Interval Debulking Surgery.

BACKGROUND/AIM: The aim of this study was to assess the value of diaphragmatic surgery to achieve optimal debulking in patients with advanced ovarian cancer treated by neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: This is a retrospective review of the medical records of 182 patients. Diaphragmatic surgery was performed during interval debulking surgery (IDS) in 74 patients between January 2002 and December 2014. The patients were divided in 2 groups: with or without histological residual diaphragmatic disease. The time-course of serum CA125 levels, cytoreductive outcome, overall survival (OS) and relapse-free survival (RFS) were analyzed. Patients without diaphragmatic peritonectomy (DP) during IDS were included in the survival analysis. RESULTS: One hundred thirty-two (72.5%) patients had FIGO stage III disease and 43 (23.6%) patients had stage IV disease. Histological examination of DP was positive in 45 patients and negative in 29 patients. CA125 normalization after the 3rd cycle of NAC was significantly associated with negative DP. OS tended to be higher in the DP-negative group (37.8 months vs 19 months, p=0.1). Median OS was 40.7 months in the case of IDS without DP and 22 months in the case of IDS with DP (p=0.048). CONCLUSION: Evaluation of residual diaphragmatic disease can be difficult after NAC. The CA125 tumor marker appears to be a useful tool to define the indications for DP. Diaphragmatic surgery after NAC may be of limited value.

Effect of concurrent radiochemotherapy and chemotherapy on serum proteins for prospective predictors of patients with HPV induced cervical cancer.

OBJECTIVES: To evaluate the effectiveness of radiochemotherapy and chemotherapy on human papilloma virus induced cervical cancer patients by the estimation of serum proteins and magnetic resonance imaging. METHODS: HPV 16/18 viral DNA was detected in the plasma of cervical cancer patients (n=50) by PCR using HPV consensus primers. Of the 50 cervical cancer patients, 25 cases undergoing radiation with chemotherapy and another 25 cases undergoing chemotherapy. Levels of pre- and post-treated serum squamous cell carcinoma antigen, soluble CD44, cancer antigen-125 were measured and evaluated the tumour size at pre- and post-radiation based on magnetic resonance images. The effectiveness of treatment was evaluated in terms of protein levels and represented as whisker line graphs. RESULTS: Of the amplified 50 samples, HPV 16 and 18 strains were identified as 48 and 44%, respectively. Serum protein levels were significantly increased in both pre-treated groups when compared to healthy group. Post-treated (radiotherapy) cervical cancer patients' shows decreased tumour size when compared to pre-treated groups. Taking consideration of proteins, squamous cell carcinoma antigen, soluble CD44, cancer antigen-125 levels are more decreased in patients treated with radiochemotherapy than chemotherapy alone. The decreased levels of proteins were significantly higher in early stage of the cervical cancer than the advanced stage of cancer patients. CONCLUSION: Serum levels of protein markers are more improved in patients treated with radiochemotherapy than chemotherapy hence, radiochemotherapy may be the best choice of treatment with reference to proteins at early stage of cervical cancer when compared to chemotherapy alone.

Increased serum-soluble interleukin-5 receptor alpha level precedes the development of eczema in children.

Interleukin-5 receptor α-subunit expression may be implicated in the development of allergic diseases. In a population-based birth cohort, we investigated the relationship between IL-5Rα and the development of allergic phenotypes in childhood, using soluble IL-5Rα (s-IL-5Rα) as a marker. Children (n = 510) were followed from birth and assessed at age 3, 5 and 8. Based on the onset and resolution of symptoms, we assigned children into the following wheeze and eczema phenotypes: never, transient, persistent, intermittent and late-onset. Specific IgE to common allergens, s-IL-5Rα (ELISA) and urinary eosinophilic protein X (U-EPX) levels was measured at age 5. s-IL-5Rα was significantly higher among atopic compared to non-atopic children (pg/ml, geometric means [95% CI], 152.4 [126.0-184.5] vs. 103.4 [94.0-113.9], p < 0.0001). While we found no association between s-IL-5Rα and current eczema at age 5, there was a significant association between eczema phenotypes and s-IL-5Rα (multiple anova model adjusted for gender and atopy, F = 2.56, p = 0.04). After adjustment for multiple comparisons, we found that children with late-onset eczema had significantly higher s-IL-5Rα compared to those who have never had eczema (mean difference [95% CI], 2.41 [1.03-5.62], p = 0.04) and those with intermittent eczema (2.63 [1.08-6.41], p = 0.02), with no difference between children who have never had eczema and other eczema phenotypes. We found no such association for wheeze phenotypes. There was a weak correlation between s-IL-5Rα and U-EPX (r = 0.16, p < 0.0001). Increased serum s-IL-5Rα level at age 5 was associated with contemporaneous atopic sensitization and with subsequent development of eczema by age 8.

Differential expression of the interleukin 5 receptor alpha isoforms in blood and tissue eosinophils of nasal polyp patients.

BACKGROUND: Given the key role of interleukin-5 (IL-5) in eosinophil function, we investigated the regulated expression of the membrane-anchored (TM-IL-5Ralpha) isoform, or a secreted (SOL IL-5Ralpha) isoform, on both protein and transcript level in vitro and in vivo. METHODS: A real-time PCR, FACS and ELISA were established to determine IL-5Ralpha isoform expression in peripheral blood and nasal tissue from control subjects and nasal polyp (NP) patients with or without asthma. Human peripheral blood eosinophils were incubated with IL-5 and were analyzed for SOL-IL-5Ralpha and TM-IL-5Ralpha mRNA and protein levels in comparison with CD-69 expression. RESULTS: SOL-IL-5Ralpha and TM-IL-5Ralpha mRNA and protein expression was significantly increased in NP vs controls. In polyp tissue, SOL-IL-5Ralpha expression correlated to disease severity and eosinophils counts, whereas TM-IL-5Ralpha levels were inversely correlated to eosinophils counts and SOL-IL-5Ralpha expression. FACS analysis revealed increased CD-69 and decreased TM-IL-5Ralpha expression in NP tissue eosinophils vs blood eosinophils. Incubation of blood eosinophils with IL-5 caused up-regulation of CD-69 and down-regulation of TM-IL-5Ralpha after 2 and 24 h. CONCLUSION: The expression of SOL-IL-5Ralpha and TM-IL-5Ralpha differs according to the eosinophil activation state and localization in the body (blood vs tissue) and may therefore be involved in the fine-tuning of the eosinophil homeostasis. Exposure of eosinophils to IL-5 reduces their responsiveness to IL-5 by regulated expression of the IL-5Ralpha isoforms. Since, TM-IL-5Ralpha is down-regulated and SOL-IL-5Ralpha (antagonistic) is upregulated in NP tissue, our findings are important to understand the clinical trials with anti-IL-5 in humans.