Seroprevalence and Cross-reactivity of Human Polyomavirus 9

Many humans have antibodies against simian lymphotropic polyomavirus (LPyV), but its DNA has not been found in humans. Identification of human polyomavirus 9 (HPyV9) led us to compare the seroprevalence and cross-reactivity of LPyV and HpyV9. Results could indicate that humans who have antibodies against LPyV are infected by HPyV9.     

Skin sensitization risk assessment: a comparative evaluation of 3 isothiazolinone biocides

Many of the chemicals in common use possess, to some degree, a capacity to cause skin sensitization. Consequently, it is important to conduct a thorough and accurate risk assessment when it can be anticipated that such chemicals are likely to come into contact with human skin. Such risk assessments must consider the nature and extent of dermal exposure together with the sensitizing potency of the chemical. Whilst the exposure elements of the risk assessment process are often well understood, or can at least be reasonably predicted on the basis of the proposed usage of the chemical, the determination of skin sensitizing potency may be problematic. In this paper, we describe an approach to the determination of relative potency of 3 isothiazolinone biocides. Initially, the local lymph node assay (LLNA) provides an estimate of relative sensitizing potency. Where appropriate, this can be followed by confirmatory testing in the human repeat insult patch test (HRIPT). The data generated reveal that (chloro)methyl isothiazolinone (CMI) is a significantly stronger sensitizer than either methyl trimethylene isothiazolinone (MTI) or benzisothiazolinone (BIT). Furthermore, both the LLNA and the HRIPT data show consistently that BIT is a somewhat weaker skin sensitizer than MTI. As an important additional component of the safety evaluation, the ability of these sensitizing isothiazolinones to cross-react has been considered; the data indicate that the more weakly sensitizing isothiazolinones do not elicit allergic reactions in subjects sensitized to MCI. The implications for use of these biocides in various product types are discussed.     

Contact allergy to isoeugenol and its derivatives: problems with allergen substitution

A total of 2261 (808 male, 1453 female) consecutive patients attending contact dermatitis clinics were patch tested to isoeugenol and its derivatives listed in the EU Inventory of Fragrance Ingredients. Positive reactions were found to isoeugenol in 40, transisoeugenol in 40, isoeugenyl acetate in 19, isoeugenyl benzoate in 4, isoeugenyl phenylacetate in 16, isoeugenyl methyl ether in 6 and benzyl isoeugenyl ether in 2 patients. There was a concomitant reaction to isoeugenol in 36/40 of those positive to transisoeugenol, 13/19 of those to isoeugenyl acetate, 3/4 of those to isoeugenyl benzoate and 15/16 of those to isoeugenyl phenylacetate but in none of those 6 positive to isoeugenyl methyl ether and in neither of those 2 positive to benzyl isoeugenyl ether. Concomitant contact allergy between isoeugenol and its derivatives may occur through chemical cross-reactivity or local skin metabolism of the derivatives. It is more commonly observed with the esters rather than the ethers. Isoeugenyl acetate has been proposed as an alternative to isoeugenol, but there is a high degree of concomitant reactivity with isoeugenol.     

Contact allergy to colour developing agents in the guinea pig

Colour developing agents, derivatives of p-phenylenediamine, can cause contact allergy. Patch test reactions to more than one colour developer are sometimes seen in patients. To study whether this is due to simultaneous sensitization or cross-reactivity, guinea pig maximization tests (GPMT) with CD-2, CD-3 and CD-4 were carried out. 5 experiments were performed, using pet. or water as vehicles. When pet. was used, the challenge concentrations could be raised and cross-reactivity between the colour developers, but not with p-phenylenediamine-dihydrochloride, was revealed. When water was used as vehicle, the challenge concentrations were limited because of staining of the test sites and irritation. CD-2, CD-3 and CD-4 were found to be extreme sensitizers according to the classification by Magnusson and Kligman. The importance of using an appropriate vehicle to obtain optimal conditions for the GPMT is stressed. To study the purity and stability of the chemicals used, analysis by HPLC of the test substances at different stages of the GPMT procedure was performed. Aqueous solutions of the colour developers were found to be unstable, while pet. mixtures were stable.     

广州地区1136例过敏患儿常见过敏原分布及尘螨交叉反应分析

目的观察广州市过敏性疾病患儿的过敏原分布及屋尘螨、粉尘螨过敏的交叉反应情况,为临床诊疗提供依据。方法采用MAST过敏原检测系统对1 136名过敏性疾病患儿(婴幼儿组278例、学龄前组455例、学龄组403例)进行35种特异性过敏原IgE检测,统计过敏原阳性率,同时分析尘螨过敏的交叉反应情况,分组间阳性率差异比较采用χ2检验。结果 1 136例过敏儿童前三位的过敏原分别是尘螨(68.13%)、家尘(49.03%)和牛奶(36.18%)。婴幼儿组前三位的过敏原分别为牛奶(70.14%)、芝士(47.84%)和全蛋(36.69%);学龄前期组前三位的过敏原分别为尘螨(80.13%)、家尘(68.35%)和牛奶(38.90%);学龄期组前三位过敏原分别为尘螨(75.93%)、家尘(40.45%)和猫毛狗毛(25.81%)。774例尘螨过敏患儿中,685例(88.50%)对粉尘螨和屋尘螨均呈阳性反应,9.56%仅对粉尘螨过敏,1.94%仅对屋尘螨过敏,各年龄组间差异无统计学意义(P>0.05)。结论广州地区过敏患儿过敏原分布较以往有一定的变化,且与国内其他地区亦存在差别。相当比例的过敏患儿对粉尘螨和屋尘螨同时阳性,仅少...     

A new mechanism shapes the naïve CD8+ T cell repertoire: the selection for full diversity

During thymic T cell differentiation, TCR repertoires are shaped by negative, positive and agonist selection. In the thymus and in the periphery, repertoires are also shaped by strong inter-clonal and intra-clonal competition to survive death by neglect. Understanding the impact of these events on the T cell repertoire requires direct evaluation of TCR expression in peripheral naïve T cells. Several studies have evaluated TCR diversity, with contradictory results. Some of these studies had intrinsic technical limitations since they used material obtained from T cell pools, preventing the direct evaluation of clonal sizes. Indeed with these approaches, identical TCRs may correspond to different cells expressing the same receptor, or to several amplicons from the same T cell. We here overcame this limitation by evaluating TCRB expression in individual naïve CD8⁺ T cells. Of the 2269 Tcrb sequences we obtained from 13 mice, 99% were unique. Mathematical analysis of the data showed that the average number of naïve peripheral CD8⁺ T cells expressing the same TCRB is 1.1 cell. Since TCRA co-expression studies could only increase repertoire diversity, these results reveal that the number of naïve T cells with unique TCRs approaches the number of naïve cells. Since thymocytes undergo multiple rounds of divisions after TCRB rearrangement and 3–5% of thymocytes survive thymic selection events the number of cells expressing the same TCRB was expected to be much higher. Thus, these results suggest a new repertoire selection mechanism, which strongly selects for full TCRB diversity.     

Cross-reactivity patterns of palladium and nickel studied by repeated open applications (ROATs) to the skin of guinea pigs

Cross-reactivity is usually studied with patch test techniques, but the relevance of a single 1-2 day exposure under occlusion can be questioned. To study relevance, animals were induced with PdCl2 or NiSO4 according to the guinea pig maximization test method and then treated for 10 days according to the repeated open application test (ROAT) method. Animals induced with PdCl2 reacted in the ROATs to PdCl2 (100%) but rarely to NiSO4. Animals induced with NiSO4 reacted in ROATs to the same degree with NiSO4 and PdCl2 (23-30%). The concordance between pre-ROAT patch test results and ROAT outcome was high for PdCl2 (100%) and low (10-40%) for NiSO4. Patch testing seems to overestimate the risk of skin reactions when guinea pigs sensitive to PdCl2 are treated topically with NiSO4. The finding from patch test studies that animals induced with NiSO4 react only to NiSO4 but not to PdCl2 was not confirmed. Repeated open applications more adequately mimic exposure conditions than does patch testing.     

Immune Memory to Sudan Virus: Comparison between Two Separate Disease Outbreaks

Recovery from ebolavirus infection in humans is associated with the development of both cell-mediated and humoral immune responses. According to recent studies, individuals that did not survive infection with ebolaviruses appear to have lacked a robust adaptive immune response and the expression of several early innate response markers. However, a comprehensive protective immune profile has yet to be described. Here, we examine cellular memory immune responses among survivors of two separate Ebolavirus outbreaks (EVDs) due to Sudan virus (SUDV) infection in Uganda—Gulu 2000–2001 and Kibaale 2012. Freshly collected blood samples were stimulated with inactivated SUDV, as well as with recombinant SUDV or Ebola virus (EBOV) GP (GP_1–649). In addition, ELISA and plaque reduction neutralization assays were performed to determine anti-SUDV IgG titers and neutralization capacity. Cytokine expression was measured in whole blood cultures in response to SUDV and SUDV GP stimulation in both survivor pools, demonstrating recall responses that indicate immune memory. Cytokine responses between groups were similar but had distinct differences. Neutralizing, SUDV-specific IgG activity against irradiated SUDV and SUDV recombinant proteins were detected in both survivor cohorts. Furthermore, humoral and cell-mediated crossreactivity to EBOV and EBOV recombinant GP_1–649 was observed in both cohorts. In conclusion, immune responses in both groups of survivors demonstrate persistent recognition of relevant antigens, albeit larger cohorts are required in order to reach greater statistical significance. The differing cytokine responses between Gulu and Kibaale outbreak survivors suggests that each outbreak may not yield identical memory responses and promotes the merits of studying the immune responses among outbreaks of the same virus. Finally, our demonstration of cross-reactive immune recognition suggests that there is potential for developing cross-protective vaccines for ebolaviruses.     

Recruitment of epitope-specific T cell clones with a low-avidity threshold supports efficacy against mutational escape upon re-infection

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