Jettanong Klaewsongkram

Krüppel-like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL-17 expression during Th17 differentiation

Krüppel‐like factor 4 (KLF4), a transcription factor, plays a key role in the pluripotency of stem cells. We sought to determine the function of KLF4 in T‐cell development and differentiation by using T‐cell‐specific Klf4‐knockout (KO) mice. We found that KLF4 was highly expressed in thymocytes and mature T cells and was rapidly down‐regulated in mature T cells after activation. In Klf4‐KO mice, we observed a modest reduction of thymocytes (27%) due to the reduced proliferation of double‐negative (DN) thymocytes. We demonstrated that a direct repression of Cdkn1b by KLF4 was a cause of decreased DN proliferation. During in vitro T‐cell differentiation, we observed significant reduction of IL‐17‐expressing CD4+ T cells (Th17; 24%) but not in other types of Th differentiation. The reduction of Th17 cells resulted in a significant attenuation of the severity (35%) of experimental autoimmune encephalomyelitis in vivo in Klf4‐KO mice as compared with the Klf4 wild‐type littermates. Finally, we demonstrated that KLF4 directly binds to the promoter of Il17a and positively regulates its expression. In summary, these findings identify KLF4 as a critical regulator in T‐cell development and Th17 differentiation.—An, J., Golech, S., Klaewsongkram, J., Zhang, Y., Subedi, K., Huston, G. E., Wood, W. H., III, Wersto, R. P., Becker, K. G., Swain, S. L., Weng, N. Krüppel‐like factor 4 (KLF4) directly regulates proliferation in thymocyte development and IL‐17 expression during Th17 differentiation. FASEB J. 25, 3634–3645 (2011). www.fasebj.org

The diagnostic value of basophil activation test in patients with an immediate hypersensitivity reaction to radiocontrast media.

BACKGROUND No available test diagnoses allergic reactions to radiocontrast media (RCM). The basophil activation test (BAT) has been introduced for the diagnosis of both immunoglobulin (Ig) E and non-IgE-dependent mast cell degranulation, but its value to diagnose immediate RCM reactions is still unknown. OBJECTIVE This study aims to evaluate the diagnostic value of BAT in immediate RCM hypersensitivity. METHODS The BATs were performed in 26 patients with immediate RCM reactions and in 43 specimens from healthy volunteers. The samples whole blood was incubated with the responsible RCM and % activated (CD63+/CCR3+) basophils were analyzed by flow cytometry. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cutoff value of activated basophils to diagnose patients with RCM hypersensitivity. RESULTS The incubation of blood with RCM yielded significantly higher activated basophil percentages in patients with a history of immediate RCM reactions than in normal controls with both 1:100 and 1:10 dilutions (13.11% vs. 2.71%, P value = .01; and 19.23% vs. 3.73%, P = .001, respectively). Both % activated basophils and stimulation index (SI) had acceptable discrimination powers to diagnose RCM hypersensitivity. The area under the curve was 0.79 (95% CI 0.67-0.91, P = .000) by using SI as the diagnostic criteria with 1:100 dilution of RCM. The specificity of the test ranged from 88.4% to 100%. CONCLUSION Our study demonstrated the potential of BAT as a diagnostic tool for an immediate RCM hypersensitivity, particularly as a confirmation test. Further studies are required to confirm the test accuracy and identify a patients predisposing factors.

Extranasal symptoms of allergic rhinitis are difficult to treat and affect quality of life

BACKGROUND Total nasal symptom score is widely used to evaluate the severity of allergic rhinitis, but the clinical significance of extranasal symptoms is largely unknown. We wished to analyze the presenting symptoms in allergic rhinitis, as well as their relationship with quality of life (QoL) and therapeutic outcomes. METHODS Presenting symptoms and QoL were assessed using the Optum™ SF-12v2(®) Health Survey in 260 patients with allergic rhinitis. Clinical response at 3 months after treatment was measured. RESULTS Ten most common symptoms presenting with at least moderate severity in allergic rhinitis were: blocked nose (82.7%), rhinorrhea (75.0%), sneeze (70.9%), itchy nose (68.5%), fatigue (63.6%), mouth breathing (61.1%), daytime somnolence (52.7%), postnasal drip (49.1%), itchy eyes (47.3%), and dry mouth (46.3%). Severity of sneeze was correlated with physical component summary (PCS) whereas postnasal drip and daytime somnolence were correlated with mental component summary (MCS). Severity of dry mouth was correlated with PCS and MCS. The symptoms with the highest severity scores after treatment were blocked nose, postnasal drip, fatigue, and dry mouth, respectively. CONCLUSIONS Extranasal symptom scores correlated well with physical health and mental health in allergic rhinitis patients. Assessment of extranasal symptoms should be included to evaluate disease severity and assess therapeutic outcomes. Clinical trial NCT02000648, http://www.clinicaltrials.gov.

The values of nasal provocation test and basophil activation test in the different patterns of ASA/NSAID hypersensitivity.

BACKGROUND The oral provocation test (OPT) is the current gold standard to diagnose aspirin hypersensitivity syndrome although it is time-consuming and contains some systemic risks. Other reliable methods with lower side effects and shorter test duration are being investigated. OBJECTIVE The purpose of this study was to evaluate the efficacy of the nasal provocation test (NPT) and the basophil activation test (BAT) in the diagnosis of different subtypes of aspirin sensitivity. METHODS Thirty aspirin sensitivity patients with cutaneous and respiratory manifestations underwent NPT and BAT with lysine-ASA. NPT result was interpreted as recommended in EAACI/GA2LEN guidelines and receiver operating characteristic analysis of BAT was performed by using 15 NSAIDs tolerant volunteers as a control group. RESULTS NPT was positive in 60% (18/30) of patients and BAT was positive in 76.7% (23/30) of patients. The incubation of basophils with 0.31 mg/ml of lysine-aspirin and using 4.6% activated basophils gives the best predictive values to diagnose aspirin sensitivity. The combination of both tests yielded positive results in 80% and 93.3% of aspirin-induced cutaneous and respiratory patterns. The agreement between NPT and BAT results was 63.3%. CONCLUSIONS NPT and BAT are beneficial to detect patients with aspirin sensitivity. The combination of both tests have additional diagnostic values; less time-consuming than OPT and their complications are negligible. A reliable alternative method with minimum side effects is needed to diagnose aspirin sensitivity in suspected patients who have contraindications for OPT.

Eosinophil Count in Nasal Mucosa Is More Suitable than the Number of ICAM-1-Positive Nasal Epithelial Cells to Evaluate the Severity of House Dust Mite-Sensitive Allergic Rhinitis: A Clinical Correlation Study

Background: House dust mite (HDM)-sensitive allergic rhinitis is a perennial rhinitis with persistent nasal inflammation. Currently, there are no reliable parameters to monitor the severity of perennial allergic rhinitis. The purpose of this study was to evaluate correlations between clinical and laboratory parameters in patients with HDM-sensitive allergic rhinitis. Methods: We measured nasal symptoms, did the Dermatophagoides pteronyssinus (Der P) skin prick test (SPT), evaluated the Der P allergen nasal challenge threshold, and laboratory parameters [(1) inflammatory cell count from nasal mucosal scraping specimens: eosinophils and neutrophils and (2) immunocytochemistry: ICAM-1 expression on nasal epithelial cells] in 20 cases of HDM-sensitive allergic rhinitis and performed correlation tests between all parameters. Results: The wheal diameter induced by Der P SPT was significantly correlated with the Der P allergen nasal challenge threshold (p = 0.001). The number of eosinophils from nasal mucosal scrapping specimens was correlated with the ICAM-1 expression on nasal epithelial cells (p = 0.039), the number of neutrophils from nasal mucosal scrapping specimens (p = 0.001), and nasal stuffiness (p = 0.037) but did not correlate with total nasal symptom scores. Conclusion: Clinical symptoms of HDM-sensitive allergic rhinitis showed a poor correlation with inflammatory parameters. The eosinophil count in nasal mucosa is correlated with ICAM-1 expression and more suitable than ICAM-1 levels to evaluate the severity of HDM-sensitive allergic rhinitis. This study also supports the role of the SPT in the diagnosis of nasal allergy to HDM.

In Vitro Test to Confirm Diagnosis of Allopurinol‐Induced Severe Cutaneous Adverse Reactions

Allopurinol is a frequent cause of severe cutaneous adverse reactions (SCARs), such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). The reactions can potentially be fatal. As drug rechallenge in patients with a history of drug‐induced SCARs is contraindicated, in vitro testing may have a diagnostic role as a confirmation test.

A Case of Sulfasalazine-Induced Hypersensitivity Syndrome Confirmed by Enzyme-Linked Immunospot Assay

A 24-year-old male with a history of spondyloarthropathy presented with high fever, cervical lymphadenopathy and generalized maculopapular rash. He was treated with prednisolone for chronic uveitis before being switched to sulfasalazine 3 weeks prior to admission. Laboratory findings revealed marked leukocytosis with frequent atypical lymphocytes. Sulfasalazine was discontinued and the etiology of mononucleosis syndrome explored. During admission, he developed acalculous cholecystitis and hypotension. All symptoms quickly improved following administration of systemic corticosteroids. The investigation for infectious mononucleosis yielded negative results and a diagnosis of sulfasalazine-induced hypersensitivity syndrome was confirmed using enzyme-linked immunospot assays.

Interleukin-2 levels in exhaled breath condensates, asthma severity, and asthma control in nonallergic asthma.

There was evidence that interleukin (IL)-2 and IL-10 in the airways play roles in regulating the asthmatic inflammatory response. The purpose of this study was to measure the levels of these cytokines in exhaled breath condensates (EBCs) from asthmatic airways and their correlation with a clinical assessment of asthma severity. The levels of IL-2 and IL-10 in EBC, Asthma Control Test (ACT) score, and the forced expiratory volume in 1 second (FEV1) were studied in 28 steroid-free asthmatic patients and 10 healthy volunteers. The results were analyzed according to their allergic status, asthma severity, and body weight. The correlations between IL-2 and IL-10 levels, percent predicted FEV1, ACT score, and body mass index were also determined. Both IL-2 and IL-10 levels in EBC significantly increased in asthmatic patients, especially in patients with moderate-to-severe persistent asthma, compared with those in normal controls. However, the signification correlations between IL-2 levels and ACT (r = -0.684; p = 0.007), as well as with percent predicted FEV1 (r = -0.671; p = 0.009), were established only in patients with nonallergic asthma. The elevation of IL-2 levels in EBC in obese subjects was observed but was probably related to asthma severity. The levels of IL-2 and IL-10 in EBC increase in asthmatic patients but only IL-2 levels significantly correlate with the ACT score and percent predicted FEV1 in nonallergic asthma. Additional studies should be explored to confirm the reliability of ACT score as a predictor of inflammatory response in asthmatic airways. Clinical trial NCT01246414, http://www.clinicaltrials.gov.

Chronic cough: an Asian perspective. Part 1: Epidemiology.

Asia is one of the most diverse and dynamic continents. Due to recent rapid industrialisation and urbanisation, morbidity patterns are likely to be diverse in Asian populations. Chronic cough is a disease condition resulting from host-environmental interactions, and is associated with a high global epidemiological burden. However, the underlying epidemiology remains unclear, particularly in Asia. We performed a literature search to identify peer-reviewed articles on chronic cough in community-based adult Asian populations that have been published between January 2000 and June 2015. In this review, we aim to examine the epidemiological characteristics and determinants of chronic cough in several geographical areas of Asia.

Lamotrigine-induced toxic epidermal necrolysis confirmed by in vitro granulysin and cytokine assays.

Lamotrigine is a recent medication which is prescribed for various neuropsychiatric conditions. It is generally well-tolerated, but recent pharmacoepidemiological evidence suggests that lamotrigine is associated with risks of developing severe cutaneous drug reactions like toxic epidermal necrolysis (TEN). However, there still remains the diagnostic challenge regarding how to confirm the drug causality in suspected cases. In most cases so far, lamotrigine causality has not been objectively demonstrated, which was possibly due to high risk of oral challenge tests or the lack of useful in vitro drug assays. Here we report a case of lamotrigine-induced TEN, of which the drug causality was confirmed by in vitro granulysin and cytokine assays.