High salivary secretory IgA antibody levels are associated with less late‐onset wheezing in IgE‐sensitized infants

To cite this article: Sandin A, Björkstén B, Böttcher MF, Englund E, Jenmalm MC, Bråbäck L. High salivary secretory IgA antibody levels are associated with less late‐onset wheezing in IgE‐sensitized infants. Pediatr Allergy Immunol 2011; 22 : 477–481. Low levels of secretory IgA (SIgA) and transient IgA deficiency have been associated with an increased risk for allergy, but data are conflicting. The aim was to assess the relationship between salivary SIgA antibody levels at 1 yr and wheezing at age four in a birth cohort, in particular the possible protective role of salivary SIgA in sensitized children. Saliva samples were obtained from all children (n = 67) with a positive skin prick test (SPT) at 1 yr and 212 children with a negative SPT. In all, 200 of these children responded to questionnaires at 4 yrs and 183 were skin prick tested at that age. The levels of salivary SIgA and salivary IgA antibodies to the most common food allergen egg and inhalant allergen cat were analyzed by ELISA. Serum was analyzed for IgE antibodies to egg and cat. Development of late‐onset wheezing was associated with low SIgA levels in children with positive SPT to at least one allergen both at 1 and 4 yrs of age (p = 0.04), as well as in children with circulating IgE antibodies to egg or cat at 1 yr (p = 0.02). None of nine persistently sensitized children with SIgA levels in the upper quartile developed wheezing, when compared to 10/20 children with lower levels (p = 0.01). Older siblings, more than three infections during infancy, at least one smoking parent, and male gender, were all associated with SIgA in the upper quartile. In conclusion, high levels of SIgA antibodies in sensitized infants were associated with significantly less late‐onset wheezing, supporting a protective role against development of asthmatic symptoms. Recurrent infections and other factors supporting an increased microbial pressure during infancy were associated with high levels of salivary SIgA.     

Murine Model for Contact Sensitization

A method combining murine ear swelling and lymph node cell proliferation was evaluated as a quantitative measurement of delayed-contact sensitization. The method involves one and/or four occluded, abdominal induction applications; use of pertussis toxin as an adjuvant; topical challenge to the ear; baseline and postchallenge ear measurements; and measurement of ¹²⁵I incorporation in axillary lymph nodes after injection of 5-[¹²⁵I]iodo-2'-deoxyuridine ([¹²⁵I]UdR). The inclusion of vehicle-induced/test chemical-challenged control groups permits objective recognition of positive responses by statistical analysis. This model—intended for use in screening for the sensitization potential of topical therapeutics—was evaluated with the known sensitizers tetracaine, naloxone, and oxazolone and with the irritant sodium dodecyl sulfate. Axillary lymph node cell proliferation measured by ¹²⁵I incorporation was a more sensitive measurement of contact sensitization than ear swelling. It was essential to perform both one and four inductions because tetracaine gave the greatest lymph node response after one induction, whereas naloxone produced a sensitization response only after four inductions. Ear swelling response to tetracaine increased after four inductions; however, ear swelling response was not observed after either one or four inductions of naloxone. After one or four inductions of the strong sensitizer, oxazolone, lymph node and ear swelling responses were observed. As expected, no significant ear swelling or lymph node response to sodium dodecyl sulfate was observed after one or four inductions. This method allows quantitative evaluation of contact sensitization by two separate measurements, thereby increasing the potential of identifying sensitizers missed by other methods.     

Skin Sensitization in School Children in Northern and Southern Norway

It has been suggested that environmental exposures and living conditions can explain some of the worldwide variation in atopic disorders. Norway has large environmental contrasts within the country. We compared skin prick sensitization rates among school children living in the southern subarctic and in the northern artic part of Norway. Approximately one quarter of the children were sensitized, mostly against pollen and animal dander, while mite and mould sensitization seemed to be a minor problem. Sensitization rates and profiles were similar in the north and south despite differences in living conditions and environmental exposures.     

Chemical allergy in humans: Fresh perspectives

Abstract

There is considerable interest in the immunobiological processes through which the development of allergic sensitization to chemicals is initiated and orchestrated. One of the most intriguing issues is the basis for the elicitation by chemical sensitizers of different forms of allergic reaction; that is, allergic contact dermatitis or sensitization of the respiratory tract associated with occupational asthma. Studies in rodents have revealed that differential forms of allergic sensitization to chemicals are, in large part at least, a function of the selective development of discrete functional sub-populations of CD4⁺ and CD8⁺ T-lymphocytes. Evidence for a similar association of chemical allergy in humans with discrete T-lymphocyte populations is, however, limited. It is of some interest, therefore, that two recent articles from different teams of investigators have shed new light on the role of polarized T-lymphocyte responses in the development of allergic contact dermatitis and occupational asthma in humans. The implications for understanding of chemical allergy in humans are explored in this Commentary.     

New opportunities in chemosensitization and radiosensitization: modulating the DNA-damage response

Many current cancer treatments, including certain classes of chemotherapeutics and radiation, induce cytotoxicity by damaging DNA. However, many cancers are resistant to these therapies, which represents a significant challenge in the clinic. Thus, modulating DNA-damage responses to selectively enhance the sensitivity of cancer cells to these therapies is highly desirable. When DNA damage is detected, DNA checkpoint mechanisms are activated to halt cells at various phases of the cell cycle. Simultaneously, DNA-damage sensors transduce signals to activate DNA-repair mechanisms via de novo expression or post-translational modification of enzymes required for DNA repair. p53 is the major player in a checkpoint that arrests cells at the G₁/S boundary, while checkpoint kinase (Chk)1 is critical for the G₂/M checkpoint and also the S checkpoint that prevents cell cycle progression after replication defects (intra-S-phase checkpoint) or S/M uncoupling (S/M checkpoint). Poly(ADP-ribose) polymerase is involved in sensing DNA single-strand breaks and inducing DNA repair via poly(ADP-ribosyl)ating various DNA-binding and DNA-repair proteins. In this review, strategies for implementing small-molecule inhibitors of poly(ADP-ribose) polymerase and Chk1, which are emerging as potential adjuncts to current therapies, are discussed.     

风湿免疫贴敷疗法治疗类骨性关节炎的临床研究

目的 探究对类骨性关节炎患者应用风湿免疫贴敷疗法的治疗效果.方法 临床纳入2015年7月至2016年6月间在本院进行治疗的类骨性关节炎患者66例,按随机投掷法给予分组,对照组33例给予常规药物治疗,研究组33例在药物治疗基础上增加免疫贴敷法,对比两组疼痛程度及疗效.结果 治疗后研究组疼痛评分为(3.32±0.42)分,明显低于对照组的(6.01±0.52)分,P＜0.05.治疗后研究组有效率为96.97％,优于对照组的78.79％,P＜0.05.结论 通过敷贴的使用增加了患者的后期疗效,缓解了疼痛程度.     

Unraveling toxicological mechanisms and predicting toxicity classes with gene dysregulation networks

The use of genes for distinguishing classes of toxicity has become well established. In this paper we combine the reconstruction of a gene dysregulation network (GDN) with a classifier to assign unseen compounds to their appropriate class. Gene pairs in the GDN are dysregulated in the sense that they are linked by a common expression pattern in one class and differ in this pattern in another class. The classifier gives a quantitative measure on this difference by its prediction accuracy. As an in‐depth example, gene pairs were selected that were dysregulated between skin cells treated with either sensitizers or irritants. Pairs with known and novel markers were found such as HMOX1 and ZFAND2A, ATF3 and PPP1R15A, OXSR1 and HSPA1B, ZFP36 and MAFF. The resulting GDN proved biologically valid as it was well‐connected and enriched in known interactions, processes and common regulatory motifs for pairs. Classification accuracy was improved when compared with conventional classifiers. As the dysregulated patterns for heat shock responding genes proved to be distinct from those of other stress genes, we were able to formulate the hypothesis that heat shock genes play a specific role in sensitization, apart from other stress genes. In conclusion, our combined approach creates added value for classification‐based toxicogenomics by obtaining novel, well‐distinguishing and biologically interesting measures, suitable for the formulation of hypotheses on functional relationships between genes and their relevance for toxicity class differences. Copyright © 2012 John Wiley & Sons, Ltd.