Cystatin SN Upregulation in Patients with Seasonal Allergic Rhinitis

Abstract

Seasonal allergic rhinitis (SAR) to the Japanese cedar, Cryptomeria japonica (JC) pollen is an IgE-mediated type I allergy affecting nasal mucosa. However, the molecular events underlying its development remain unclear. We sought to identify SAR-associated altered gene expression in nasal epithelial cells during natural exposure to JC pollen. We recruited study participants in 2009 and 2010 and collected nasal epithelial cells between February and April, which is the period of natural pollen dispersion. Fifteen patients with SAR-JC and 13 control subjects were enrolled in 2009, and 17 SAR-JC patients, 13 sensitized asymptomatic subjects (Sensitized), and 15 control subjects were enrolled in 2010. Total RNA was extracted from nasal epithelial cells and 8 SAR-JC patients and 6 control subjects in 2009 were subjected to microarray analysis with the Illumina HumanRef-8 Expression BeadChip platform. Allergen-stimulated histamine release was examined in the peripheral blood basophils isolated from patients with SAR. We identified 32 genes with significantly altered expression during allergen exposure. One of these, CST1 encodes the cysteine protease inhibitor, cystatin SN. CST1 expression in nasal epithelial cells was significantly upregulated in both the 2009 and 2010 SAR-JC groups compared with the control groups. Immunohistochemical staining confirmed the increased expression of CST1 in the nasal epithelial cells of SAR patients. Addition of exogenous CST1 to basophils inhibited JC allergen-stimulated histamine release in vitro. We propose that CST1 may contribute to inactivation of protease allergens and help re-establish homeostasis of the nasal membranes.

Airway Epithelial Expression Quantitative Trait Loci Reveal Genes Underlying Asthma and Other Airway Diseases

“…In addition, CST1 expression was increased in patients with seasonal allergic rhinitis (80). Importantly, these two eQTLs are trans-activating and airway specific and were not discovered by previous eQTL studies.…”

The nasal methylome and childhood atopic asthma

“…Our findings demonstrate a clear relationship between DNA methylation and gene expression in the nasal epithelia of young allergic asthmatics using a stringent analytical pipeline to ensure that methylation changes we identified are not false positives due to influence of demographic factors or technical variables. More than half of the differentially expressed genes in our analysis have significant associations with methylation marks; this includes asthma and allergy genes ALOX15 (40), CAPN14 (41), CTSC (42) , CST1 (43) , GSN (44) , NTRK2 (45) , and VWF (46) as well as a number of immune and extracellular matrix genes. Moreover, genes have previously identified as differentially expressed in the respiratory epithelia but did not reach statistical significance in our expression analysis, such as periostin(15, 17), are also differentially methylated.…”

Emerging Role of Human Basophil Biology in Health and Disease

“…Late-phase hypersensitivity reactions (LPR) occur approximately 6–12 h after an immediate hypersensitivity reaction, and can be observed in allergic rhinitis and severe asthma, and perhaps occur in the context of some urticarias and atopic dermatitis [4–9, •89–91]. The potential contribution of basophils to LPR is based on their presence in target tissues within hours following experimental allergen challenge [6–8, 11, •87, 88, 91].…”

“…The potential contribution of basophils to LPR is based on their presence in target tissues within hours following experimental allergen challenge [6–8, 11, •87, 88, 91]. In cutaneous allergen challenges, the LPR may be comprised of up to 50 % basophils [7, 8, •89].…”

“…Additionally, in post mortem assessment, lungs of patients with fatal asthma were found to have significantly more basophils than those who died from other causes [93]. The increase in IL-4 in LPR, and the demonstrated capacity for activated basophils to produce large quantities of IL-4, provide correlative evidence for basophils playing an important role in the pathophysiology of LPR with propagation of Th2 immune responses [1, 4, 72, •89–91, •94, -95]. …”