Research Article: Role of offending out-door aero-allergen and CD14 C(-159)T polymorphism in development and severity of asthma in a Kolkata patient population

Date Published: December , 2017

Publisher: Makerere Medical School

Author(s): Shampa Dutta, Priti Mondal, Nimai Chandra Saha, Saibal Moitra, Sanjoy Podder, Amlan Ghosh, Goutam Kumar Saha.

http://doi.org/10.4314/ahs.v17i4.18

Abstract

Present study involved identification of offending out-door aero-allergens and associated genetic pathway in nasso-bronchial asthma among Kolkata population.

Skin-prick test was done among 950 asthmatic patients against 11 common aero-allergens and total serum IgE concentration was measured. PCR-RFLP was done in patients and non-asthmatic control (n=220 in each) to characterize functional polymorphism, C(-159)T, of CD14, a positional candidate gene for allergy. Association of genetic polymorphisms was made with clinico-pathological conditions.

We identified Cocos nucifera as the most common aero-allergen sensitizer among atopic patients in Kolkata. Patients with childhood-onset asthma were significantly more sensitive towards aero-allergens and had significantly higher serum IgE level than those of adult-onset (p< 0.0001). No significant difference was found in distribution of SNP genotypes of CD14 among case and control (p=0.178). However among patients, frequency of C allele is significantly higher in childhood-onset group than that of adult-onset and concordantly in former CC genotype was associated with significant higher level of serum IgE than CT and TT. In Kolkata, pollen is a common out-door aero-allergen and Cocos nucifera is predominant among pollens. Childhood-onset and adult-onset of asthma showed significant difference in allergen sensitivity as well as genetic background with respect to CD14 polymorphism.

Partial Text

Asthma is the most common type of atopic manifestation characterized by respiratory symptoms, narrowing of airways, and inflammation1. Prevalence of asthma is gradually increasing worldwide including developing countries and in India alone, roughly 15% of the people suffer from this disease2,3. Development of asthma in individual depends on both environmental stimuli like aero-allergen and genetic factors4. Exposure of aero-allergen serves as a trigger for worsening of asthma and therefore identification of disease specific allergen is important for designing avoidance strategy5. Airborne pollens and molds produced by flowering plants and fungi are the most important factors of asthma and India being a climatically diverse country supports huge diversity of such aero-allergens in different regions. In asthma, atopic response is characterized by allergic inflammation induced by Th2 (T-helper type-2) derived cytokines and production of allergen specific immunoglobulin-E (IgE)6. The gene encoding Cluster Differentiation antigen (CD14) is localized on chromosomal 5q31.1 region which is associated with both asthma and total serum IgE concentration7. Actually CD14 is a pattern recognition factor that plays a central role in innate immunity through recognition of bacterial lipopolysaccharide (LPS) leading to Th1 differentiation and suppression of Th2-dependent IgE responses8.

With a background of increased incidence of bronchial asthma in Kolkata population, this study aimed to analyze environmental and genetic factors influencing such multifactorial disease condition. Among total 11 common out-door aero-allergens sensitizers (6 pollen and 5 molds), the most predominant one found in this analysis was Cocos nucifera followed by Caesalpenia sp, Caricapa paya etc, all of which belong to pollen category. This finding is in agreement with our previous study2 indicating that pollen category is a more predominant aero-allergen over mold category in out-door air of Kolkata. On the contrary, mold category was found to be more common over pollen among asthmatic patients of South-Western Iran18 indicating importance of geographic location and associated conditions in this respect. A cross reactivity of Cocos nucifera with Areca catechue, Phoenix sylvestris and some other members of Palmacae family was reported19 from Eastern India. Surprisingly, very low skin sensitivity of both Areca and Phoenix as compared to Cocos nucifera did not support such cross reactivity in our study population. In the present study, significantly higher numbers of skin test positive patients along with concordant higher level of total serum IgE were found among child and adolescents than in adults and this was preliminarily, in accordance, to the idea20 of decline of asthma incidence and severity with age (Cut off values for normal IgE leveling blood: 4–10 years, <250IU/ml; 10–16 years, <200IU/ml;adults, <100IU/ml21). However, significant difference of skin test sensitivity and total IgE between childhood onset and adult onset groups imposed more importance on age of disease onset and some differential genetic interplay might be involved forsuch phenotypic heterogeneity. Similarly, Segala et al (2000)22 found phenotypic heterogeneity between childhood onset and adult onset asthma and reported comparatively more severity in adults having their disease onset in childhood. Aero-allergens of pollen category seemed to be more prevalent and cause more severe sensitization in Kolkata metropolis than that of mold. This might have implications in designing preventive strategies. Childhood onset asthma seemed to be more severe than that of adult onset and this might have some genetic background. Therefore effective treatment plan should be designed separately for these two disease sub-sets in accordance.   Source: http://doi.org/10.4314/ahs.v17i4.18

 

Leave a Reply

Your email address will not be published.