HLA-associated outcomes in peanut oral immunotherapy trials identify mechanistic and clinical determinants of therapeutic success.

Rationale: Previous studies identified an interaction between HLA and oral peanut exposure. HLA-DQA1*01:02 had a protective role with the induction of Ara h 2 epitope-specific IgG4 associated with peanut consumption during the LEAP clinical trial for prevention of peanut allergy, while it was a risk allele for peanut allergy in the peanut avoidance group. We have now evaluated this gene-environment interaction in two subsequent peanut oral immunotherapy (OIT) trials - IMPACT and POISED - to better understand the potential for the HLA-DQA1*01:02 allele as an indicator of higher likelihood of desensitization, sustained unresponsiveness, and peanut allergy remission. Methods: We determined HLA-DQA1*01:02 carrier status using genome sequencing from POISED (N=118, age: 7-55yr) and IMPACT (N=126, age: 12-<48mo). We tested for association with remission, sustained unresponsiveness (SU), and desensitization in the OIT groups, as well as peanut component specific IgG4 (psIgG4) using generalized linear models and adjusting for relevant covariates and ancestry. Results: While not quite statistically significant, a higher proportion of HLA-DQA1*01:02 carriers receiving OIT in IMPACT were desensitized (93%) compared to non-carriers (78%); odds ratio (OR)=5.74 (p=0.06). In this sample we also observed that a higher proportion of carriers achieved remission (35%) compared to non-carriers (22%); OR=1.26 (p=0.80). In POISED, carriers more frequently attained continued desensitization (80% versus 61% among non-carriers; OR=1.28, p=0.86) and achieved SU (52% versus 31%; OR=2.32, p=0.19). psIgG4 associations with HLA-DQA1*01:02 in the OIT arm of IMPACT which included younger study subjects recapitulated patterns noted in LEAP, but no associations of note were observed in the older POISED study subjects. Conclusions: Findings across three clinical trials show a pattern of a gene environment interaction between HLA and oral peanut exposure. Age, and prior sensitization contribute additional determinants of outcomes, consistent with a mechanism of restricted antigen recognition fundamental to driving protective immune responses to OIT.

Allergen immunotherapy for the prevention of allergic disease: protocol for a systematic review.

BACKGROUND: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for the Prevention of Allergic Disease. We seek to critically assess the effectiveness, cost-effectiveness, and safety of AIT in the prevention of allergic disease. METHODS: We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesized. DISCUSSION: The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.

A Prospective Study of Demographic Features and Quality of Life in HIV-Positive Women with Cervical Cancer Treated at Tygerberg Hospital

Background: Cervical cancer and human immunodeficiency virus (HIV) infection/acquired immune deficiency syndrome (AIDS) both have a high incidence in South Africa. Cervical cancer treatment of HIV-positive women poses challenges. Treatment-related changes in quality of life (QOL) of such women are important to future treatment protocols.Aim: To examine demographic data of HIV-negative and HIV-positive women at diagnosis of cervical cancer and describe their changes in QOL as a result of treatment.Methods and materials: All newly diagnosed patients with cervical cancer at Tygerberg Hospital were approached to participate in the study. The European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) and the Cervix Cancer Module (QLQ-CX24) were used. General QOL was measured with the EORTC QLQ-C30 and cervical-specific QOL with the QLQ-CX24 questionnaire. The patients completed the questionnaire at diagnosis; on completion of treatment and at 3 months' follow-up.Results: The study included a total of 221 women of whom 22% were HIV-positive; the latter were younger and of higher educational level than the rest. Mean monthly income and stage distribution was similar between the two groups. HIV-positive patients underwent radiation therapy more commonly than chemoradiation. HIV-positive women showed statistically significantly higher loss to follow-up during the study. HIV-positive women experienced no improvement in insomnia; appetite loss; nausea; vomiting; diarrhoea; social role or any of the sexual domains. In contrast; HIV-negative women experienced statistically significant improvement in all sexual domains other than sexual/vaginal functioning. The QOL improvement of HIV-negative women was statistically significantly greater than their HIV-positive counterparts in the majority of QOL domains. Global health improved in both groups; with HIV-negative women experiencing greater improvement. HIV-positive women experienced an initial decline of peripheral neuropathy (PN) symptoms post treatment with a return to pretreatment values at 3 months' follow-up. The change in PN was statistically significant between the HIV-negative and HIV-positive women.Conclusion: Demographic differences exist between the HIV-negative and HIV-positive groups. The differential outcome in the QOL of HIV-positive and HIV-negative women treated for cervical cancer might be related to persistence of AIDS-related symptoms on completion of cervical cancer treatment

Explaining adherence to self-care behaviours amongst adolescents with food allergy: a comparison of the health belief model and the common sense self-regulation model.

OBJECTIVES: To identify explanations for adherence to self-care behaviours amongst adolescents with food allergy-induced anaphylaxis using two social cognition models: the health belief model (HBM) and the common sense self-regulation model (CS-SRM). DESIGN: Cross-sectional self-completion questionnaire study to gain initial evidence of the two models' feasibility/effectiveness in explaining adherence in an adolescent food-allergic population. METHODS: Participants aged 13-19 years with a diagnosis of severe food allergy and a prescription of an adrenaline auto-injector were recruited from hospital outpatients. Adherence to self-care behaviours was measured in addition to constructs from the HBM and CS-SRM. RESULTS: One hundred and eighty-eight food-allergic adolescents completed the questionnaire. The HBM, specifically the constructs perceived severity and barriers, accounted for 21% of the explained variance in adherence behaviours. CS-SRM constructs, illness identity, timeline cyclical beliefs and emotional representations explained 25% of the variance. CONCLUSIONS: Both models performed similarly in explaining adherence to self-care behaviours in adolescents with food allergy. Interventions designed to elicit personal barriers to adherence and to address perceptions of severity and the unpredictable nature of symptoms may be more effective in improving adherence to self-care behaviours than current interventions.

Pathophysiology, diagnosis and management of exercise-induced anaphylaxis.

PURPOSE OF REVIEW: The aim of this review is to challenge the current opinions of the pathophysiological mechanisms that give rise to food dependent exercise-induced anaphylaxis (FDEIA) and to consider these mechanisms within the wider context of exercise physiology to further inform our understanding and treatment of this condition. RECENT FINDINGS: Exercise-induced anaphylaxis (food dependent and nonfood dependent) is a clinical syndrome in which anaphylaxis occurs in conjunction with exercise. Given the rarity of the condition, our current understanding relies on the many case studies and reviews of the topic. The pathophysiology of FDEIA remains to be fully elucidated with well constructed trials but current working hypotheses to date involve alterations in plasma osmolaltiy and pH, tissue enzyme activity, blood flow redistribution, altered gastrointestinal permeability and facilitated epitope recognition/allergen binding. SUMMARY: Implications for future research are the physiological changes that occur during exercise need deeper consideration to ensure that proposed mechanisms are realistic and actually occur within the time frame and exercise-intensity domain during which the reported FDEIA occurred. These theories must be tested rigorously with sufficiently powered studies if progress is to be made in determining the perplexing pathophysiology of FDEIA.

Low prevalence of latex sensitivity in South African spina bifida children in Cape Town.

Spina bifida children have a high prevalence of latex allergy in studies reported from Europe and the USA. This study investigated the prevalence of latex allergy in a cohort of 24 spina bifida children at the Red Cross Children's Hospital from Cape Town, South Africa. The children were investigated using a detailed questionnaire, skin prick tests (ALK-Abello), ImmunoCap RASTs, Western blotting and ELISA, using the purified latex proteins Hev b1 and Hev b3 and whole latex preparation. A low overall prevalence of latex sensitization of 16.7% was found in the children. Children who were sensitive reacted to water insoluble to Hev b1 and Hev b3 proteins. The low prevalence of latex sensitization in the South African children may not be entirely explained by stringent latex avoidance. The children were from a low socioeconomic social status and 'hygiene' and other factors should be considered.