Long term intrinsic cycling in human life course antibody responses to influenza A(H3N2): an observational and modeling study.

Background: Over a life course, human adaptive immunity to antigenically mutable pathogens exhibits competitive and facilitative interactions. We hypothesize that such interactions may lead to cyclic dynamics in immune responses over a lifetime. Methods: To investigate the cyclic behavior, we analyzed hemagglutination inhibition titers against 21 historical influenza A(H3N2) strains spanning 47 years from a cohort in Guangzhou, China, and applied Fourier spectrum analysis. To investigate possible biological mechanisms, we simulated individual antibody profiles encompassing known feedbacks and interactions due to generally recognized immunological mechanisms. Results: We demonstrated a long-term periodicity (about 24 years) in individual antibody responses. The reported cycles were robust to analytic and sampling approaches. Simulations suggested that individual-level cross-reaction between antigenically similar strains likely explains the reported cycle. We showed that the reported cycles are predictable at both individual and birth cohort level and that cohorts show a diversity of phases of these cycles. Phase of cycle was associated with the risk of seroconversion to circulating strains, after accounting for age and pre-existing titers of the circulating strains. Conclusions: Our findings reveal the existence of long-term periodicities in individual antibody responses to A(H3N2). We hypothesize that these cycles are driven by preexisting antibody responses blunting responses to antigenically similar pathogens (by preventing infection and/or robust antibody responses upon infection), leading to reductions in antigen-specific responses over time until individual's increasing risk leads to an infection with an antigenically distant enough virus to generate a robust immune response. These findings could help disentangle cohort effects from individual-level exposure histories, improve our understanding of observed heterogeneous antibody responses to immunizations, and inform targeted vaccine strategy. Funding: This study was supported by grants from the NIH R56AG048075 (DATC, JL), NIH R01AI114703 (DATC, BY), the Wellcome Trust 200861/Z/16/Z (SR), and 200187/Z/15/Z (SR). This work was also supported by research grants from Guangdong Government HZQB-KCZYZ-2021014 and 2019B121205009 (YG and HZ). DATC, JMR and SR acknowledge support from the National Institutes of Health Fogarty Institute (R01TW0008246). JMR acknowledges support from the Medical Research Council (MR/S004793/1) and the Engineering and Physical Sciences Research Council (EP/N014499/1). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

The relationship between motor development and social adaptability in autism spectrum disorder.

Objectives: Autism spectrum disorders(ASD)describe a wide range of pervasive developmental disorders by core symptoms including deficits in social communication and interaction, as well as restricted, repetitive, and stereotyped behaviors. At the same time, some children with autism are accompanied by motor development disorder. Many studies have confirmed that the motor development impairment was significantly associated with the social problems associated with ASD. Thus, this study aimed to investigate how motor development affects social adaptability in children with ASD to provide references for early ASD intervention. Materials and methods: The case data of children's health care were selected in 2021. Motor development was assessed with the Developmental Behavior Assessment Scale for Children Aged 0-6 years. Social adaptability was measured using the Japanese S-M Social Living Skills Scale. Statistical analysis was conducted with SPSS 22.0 software package. Data were analyzed using independent samples t-test and logistic regression. Results: A total of 198 cases comprising 140 boys (70.71%) and 58 girls (29.29%) were included, and the average age of participants was 3.40 ± 1.06 years, with 3.33 ± 1.18 years in the typical development (TD) children group and 3.46 ± 0.95 years in the ASD group. The social adaptability of 107 ASD children was abnormal, including 37 children (34.5%) with marginal, 48 children (44.9%) with mild, 17 children (15.9%) with moderate, and 5 children (4.7%) with severe. In 91 TD children, there were 51 children (56.04%) with normal social adaptability, 38 children (41.75%) with marginal, 2 children (2.19%) with mild, and nobody with moderate or severe. The ASD children had lower levels of developmental behavior than those of TD children, and the difference was statistically significant. The results of logistic regression showed that fine motor increased by 1 unit, and the OR value of one level decreased in social adaptability was 2.24 times (OR = e0.807 = 2.24). Conclusion: In children with ASD, not only motor development is delayed, but also social adaptability is affected, and fine motor skill may be important for social adaptability.

A female case with novel KDM5C heterozygous variation presenting with Claes-Jensen type-like phonotype.

BACKGROUND: Lysine(K)-specific demethylase 5C (KDM5C) dysfunction causes X-linked syndromic intellectual developmental disorder Claes-Jensen type in male patients. The clinical presentations of female individuals with heterozygous KDM5C variations vary widely and are only now beginning to be characterized in detail. CASE PRESENTATION: Herein, we identified a novel de novo heterozygous nonsense variation of KDM5C (c.3533C > A, p.S1178X) in a sporadic 4-year-old Chinese girl, who presented with Claes-Jensen type-like phenotypes, such as moderate developmental delay, serious expressive language delay, short stature, microcephaly, and typical facial particularities. Moreover, X-chromosome inactivation (XCI) analysis showed no significant skewed X-inactivation. CONCLUSION: The report expands the genotype of KDM5C variation in female patients, delineates the phenotype of affected females in this well-known X-linked disorder, and also reinforces the necessity to consider this X-linked gene, KDM5C, in sporadic female patients.