Atopic dermatitis (AD) has a well-established association with skin colonization or infection by Staphylococcus aureus, which can exacerbate the disease. However, a causal relationship between specific changes in skin colonization during the first years of life and AD development still remains unclear. In this prospective birth cohort study, we aimed to characterize the association between skin colonization and AD development in 149 white infants with or without a family history of atopy. We assessed infants clinically and collected axillary and antecubital fossa skin swabs for culture-based analysis at birth and at seven time points over the first 2 years of life. We found that at age 3 months, S. aureus was more prevalent on the skin of infants who developed AD later on. S. aureus prevalence was increased on infants' skin at the time of AD onset and also 2 months before it, when compared with age-matched, unaffected infants. Furthermore, at AD onset, infants testing positive for S. aureus were younger than uncolonized subjects. In conclusion, our results suggest that specific changes in early-life skin colonization may actively contribute to clinical AD onset in infancy.

Celiac sprue (also known as celiac disease) is an inheritable, gluten-induced enteropathy of the upper small intestine with an estimated prevalence of 0.5%-1% in most parts of the world. The ubiquitous nature of food gluten, coupled with inadequate labeling regulations in most countries, constantly poses a threat of disease exacerbation and relapse for patients. Here, we demonstrate that a two-enzyme cocktail comprised of a glutamine-specific cysteine protease (EP-B2) that functions under gastric conditions and a PEP, which acts in concert with pancreatic proteases under duodenal conditions, is a particularly potent candidate for celiac sprue therapy. At a gluten:EP-B2:PEP weight ratio of 75:3:1, grocery store gluten is fully detoxified within 10 min of simulated duodenal conditions, as judged by chromatographic analysis, biopsy-derived T cell proliferation assays, and a commercial antigluten antibody test.

CD8؉ cytotoxic T lymphocytes (CTL) can recognize and kill target cells expressing only a few cognate major histocompatibility complex (

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The influence of environmental factors on atopic dermatitis (AD) has been investigated in many cross-sectional studies. It remains however unclear if they could influence AD development early in life. This prospective birth cohort study aimed to monitor aspects of family lifestyle and child's nutrition within a Caucasian population and to assess its association with AD development over the first two years of life. Genetic predisposition was evaluated based on family history and profilaggrin genotyping. Of 149 included children, 36 developed AD.Infants with a family history of atopy developed AD 2.6 times more frequently (30 of 97) than infants without atopic predisposition (6 of 52). Genotyping was carried out on 50% of the children included. Profilaggrin mutations (R501X, 2282del4, R2447X and S3247X) were infrequent in our population. Lower incidence of AD was observed in infants exposed to a damp housing environment, lower household income and smoking mothers with a higher but not with a lower education level. Conclusion :Family history of atopy was a significant risk factor for AD regardless of the most common, currently defined, FLG mutations. Humidity at home and passive smoking seem associated with AD development in infancy.

In almost half of patients diagnosed with Hodgkin’s disease (HD), the malignant Reed-Sternberg (RS) cells express Epstein-Barr virus (EBV) antigens. Multiple translational efforts are actively investigating antitumor immune strategies by stimulating cytotoxic T lymphocytes (CTL) against tumor-associated EBV antigens. It has previously been believed that this therapeutic strategy and presence of EBV-specific CTLs are limited to EBV-positive HD. In an effort to explore the EBV-specific immune response, here we characterize EBV-specific CTL responses to lytic and latent EBV antigens in 12 consecutive EBV carriers with EBV-negative HD. Compared to healthy donors, we detected weak, baseline EBV-specific responses to both lytic and latent antigens by IFN-γ ELISPOT in patients with EBV-negative HD at diagnosis. Chemoradiotherapy was associated temporally with a decrease EBV-specific responses. At final follow-up (24 months), recovery of EBV-specific CTL responses was observed with robustness of lytic-specific response equivalent to healthy controls. We confirm evidence of EBV-specific CTLs in patients with EBV-negative HD and provide the first report of dynamic variance in this population during treatment. Our observation challenges prior belief that patients with HD remain immunodeficient following therapy and argues that the clinical significance of the EBV-specific immune response in EBV-negative HD should be further investigated.

Imatinib mesylate, a selective inhibitor of the bcr/abl tyrosine kinase, has revolutionized the treatment of CML and is the first-line therapy for most patients. Most CML patients in chronic phase achieve hematologic remission under treatment with imatinib, with up to 70% also achieving cytogenetic remission. However, imatinib therapy is not curative, as patients who discontinue the drug invariably relapse. Thus, the need to find alternate, potentially curative therapies remains. Low levels of CD8+ T cell responses to certain HLA restricted peptides have been detected in CML patients after successful treatment. To determine, if CML patients in remission on imatinib develop and sustain anti-leukemia CD4+ or CD8+ T cell responses, blood samples from patients before and several time points after treatment were collected and analyzed. Pre-treatment samples were utilized as sources of autologous leukemic cells to detect anti-leukemia T cell responses in post-treatment remission samples. Autologous leukemic samples alone and remission samples alone served as controls. In 7 of the 14 patients investigated, significant IFN-γ responses (p<0.01) in ELISPOT assay were detectable when patients achieved cytogenetic remission, and peaked at 10–15 months (median 36 SFCs, range 26–71 SFCs), before they slowly decreased (up to 46 months post-treatment) to levels similar to those from leukemic samples alone and remission samples alone (6 SFCs, range 0–13 SFCs). These results correlated with T cell responses in cytokine flow cytometry (TNF-α 1.4–40%, IFN-γ 1.0–6.6%, p<0.05), and showed a predominance for CD4+ T cells. Furthermore, TNF-α and IFN-γ production (p<0.05) was confirmed in CD4+ and CD8+ T cell clones generated in a remission sample from one patient using multiplex cytokine assay: 6.43–37.90 pg/ml for TNF-α, 14.90–110.42 pg/ml for IFN-γ. CD8+ T cell clones (HLA-A0201+) were tested for reactivity against HLA-A0201 restricted peptides derived from leukemia associated antigens proteinase 3, Wilms tumor 1 and bcr/abl, as well as tumor associated antigens p53, p68, and human telomerase (hTERT) in IFN-γ ELISPOT assays. No IFN-γ responses were detected in the CD8+ T cell clones when stimulated with the peptides compared to stimulation with an irrelevant peptide (0–15 SFCs, p=0.55), suggesting that these clones react to as yet to be defined leukemia associated antigens. Together, these data show that CD4+ T cells play an important role in anti-leukemia immune responses in patients in remission (sustained over time) and might contribute to killing of leukemic cells, possibly via TNF-α. Banked autologous leukemic cells could be used for vaccination of CML patients in order to enhance anti-leukemia T cell responses and may, in combination with imatinib, lead to eradication of residual leukemic cells with a durable cure.