A low-frequency IL4R locus variant in Japanese patients with intravenous immunoglobulin therapy-unresponsive Kawasaki disease

Background: Kawasaki disease (KD) is a systemic vasculitis which may be associated with coronary artery aneurysms. A notable risk factor for the development of coronary artery aneurysms is resistance to intravenous immunoglobulin (IVIG) therapy, which comprises standard treatment for the acute phase of KD. The cause of IVIG resistance in KD is largely unknown; however, the contribution of genetic factors, especially variants in immune-related genes, has been suspected. Methods: To explore genetic variants related to IVIG-unresponsiveness, we designated KD patients who did not respond to both first and second courses of IVIG therapy as IVIG-unresponsive patients. Using genomic DNA from 30 IVIG-unresponsive KD patients, we performed pooled genome sequencing targeting 39 immune-related cytokine receptor genes. Results: The single nucleotide variant (SNV), rs563535954 (located in the IL4R locus), was concentrated in IVIG-unresponsive KD patients. Individual genotyping showed that the minor allele of rs563535954 was present in 4/33 patients with IVIG-unresponsive KD, compared with 20/1063 individuals in the Japanese genome variation database (odds ratio = 7.19, 95% confidence interval 2.43-21.47). Furthermore, the minor allele of rs563535954 was absent in 42 KD patients who responded to IVIG treatment (P = 0.0337), indicating that a low-frequency variant, rs563535954, is associated with IVIG-unresponsiveness in KD patients. Although rs563535954 is located in the 3'-untranslated region of IL4R, there was no alternation in IL4R expression associated with the mior allele of rs563535954. However, IVIG-unresponsive patients that exhibited the minor allele of rs563535954 tended to be classified into the low-risk group (based on previously reported risk scores) for prediction of IVIG-resistance. Therefore, IVIG-unresponsiveness associated with the minor allele of rs563535954 might differ from IVIG-unresponsiveness associated with previous risk factors used to evaluate IVIG-unresponsiveness in KD. Conclusion: These findings suggest that the SNV rs563535954 could serve as a predictive indicator of IVIG-unresponsiveness, thereby improving the sensitivity of risk scoring systems, and may aid in prevention of coronary artery lesions in KD patients.ArticlePEDIATRIC RHEUMATOLOGY.17:34(2019)journal articl

Comparison of weighed food record procedures for the reference methods in two validation studies of food frequency questionnaires

Background: Although open-ended dietary assessment methods, such as weighed food records (WFRs), are generally considered to be comparable, differences between procedures may influence outcome when WFRs are conducted independently. In this paper, we assess the procedures of WFRs in two studies to describe their dietary assessment procedures and compare the subsequent outcomes. Methods: WFRs of 12 days (3 days for four seasons) were conducted as reference methods for intake data, in accordance with the study protocol, among a subsample of participants of two large cohort studies. We compared the WFR procedures descriptively. We also compared some dietary intake variables, such as the frequency of foods and dishes and contributing foods, to determine whether there were differences in the portion size distribution and intra- and inter-individual variation in nutrient intakes caused by the difference in procedures. Results: General procedures of the dietary records were conducted in accordance with the National Health and Nutrition Survey and were the same for both studies. Differences were seen in 1) selection of multiple days (non-consecutive days versus consecutive days); and 2) survey sheet recording method (individual versus family participation). However, the foods contributing to intake of energy and selected nutrients, the portion size distribution, and intra- and inter-individual variation in nutrient intakes were similar between the two studies. Conclusion: Our comparison of WFR procedures in two independent studies revealed several differences. Notwithstanding these procedural differences, however, the subsequent outcomes were similar

Future change of daily precipitation indices in Japan: a stochastic weather generator-based bootstrap approach to provide probabilistic climate information

This study proposes the stochastic weather generator (WG)-based bootstrap approach to provide the probabilistic climate change information on mean precipitation as well as extremes, which applies a WG (i.e., LARS-WG) to daily precipitation under the present-day and future climate conditions derived from dynamical and statistical downscaling models. Additionally, the study intercompares the precipitation change scenarios derived from the multimodel ensemble for Japan focusing on five precipitation indices (mean precipitation, MEA; number of wet days, FRE; mean precipitation amount per wet day, INT; maximum number of consecutive dry days, CDD; and 90th percentile value of daily precipitation amount in wet days, Q90). Three regional climate models (RCMs: NHRCM, NRAMS and TWRF) are nested into the high-resolution atmosphere-ocean coupled general circulation model (MIROC3.2HI AOGCM) for A1B emission scenario. LARS-WG is validated and used to generate 2000 years of daily precipitation from sets of grid-specific parameters derived from the 20-year simulations from the RCMs and statistical downscaling model (SDM: CDFDM). Then 100 samples of the 20-year of continuous precipitation series are resampled, and mean values of precipitation indices are computed, which represents the randomness inherent in daily precipitation data. Based on these samples, the probabilities of change in the indices and the joint occurrence probability of extremes (CDD and Q90) are computed. High probabilities are found for the increases in heavy precipitation amount in spring and summer and elongated consecutive dry days in winter over Japan in the period 2081-2100, relative to 1981-2000. The joint probability increases in most areas throughout the year, suggesting higher potential risk of droughts and excess water-related disasters (e. g., floods) in a 20 year period in the future. The proposed approach offers more flexible way in estimating probabilities of multiple types of precipitation extremes including their joint probability compared to conventional approaches

Combination Therapy of Cyclosporin A and Plasma Exchange for Infants with Immunoglobulin-resistant Kawasaki Disease

Article信州医学雑誌 70(4) : 225-231(2022)departmental bulletin pape