Primary Antibody Immunodeficiency and the Pregnant Patient.

An overview of primary antibody immunodeficiency in pregnancy is presented. Indications for immunoglobulin replacement therapy (IGRT), dosing, and safety considerations are highlighted. Uses of immunizations and antimicrobial therapy are also discussed. In general, IGRT, both intravenous and subcutaneous, is considered safe in pregnancy.

Characterization of Infants with Idiopathic Transient and Persistent T Cell Lymphopenia Identified by Newborn Screening-a Single-Center Experience in New York State.

PURPOSE: Newborn screening (NBS) quantifies T cell receptor excision circles (TREC) and identifies infants with T cell lymphopenia (TCL). This study elucidates the demographics, laboratory characteristics, genetics, and clinical outcomes following live viral vaccine administration of term infants with transient or persistent idiopathic TCL. METHODS: A single-center retrospective analysis was performed from September 2010 through June 2018. Laboratory variables were compared with Mann-Whitney tests. Correlations between initial TREC levels and T cell counts were determined by Spearman tests. RESULTS: Twenty-two transient and 21 persistent TCL infants were identified. Males comprised 68% of the transient and 52% of the persistent TCL cohorts. Whites comprised 23% of the transient and 29% of the persistent cohorts. Median initial TREC levels did not differ (66 vs. 60 TRECs/µL of blood, P = 0.58). The transient cohort had higher median initial CD3+ (2135 vs. 1169 cells/µL, P < 0.001), CD4+ (1460 vs. 866 cells/µL, P < 0.001), and CD8+ (538 vs. 277 cells/µL, P < 0.001) counts. The median age of resolution for the transient cohort was 38 days. Genetic testing revealed 2 genes of interest which warrant further study and several variants of uncertain significance in immunology-related genes in the persistent cohort. 19 transient and 14 persistent subjects received the initial rotavirus and/or MMRV immunization. No adverse reactions to live viral vaccines were reported in either cohort. CONCLUSION: Transient and persistent TCL infants differ by demographic, laboratory, and clinical characteristics. Select transient and persistent TCL patients may safely receive live attenuated viral vaccines, but larger confirmatory studies are needed.

Pathophysiology of Non-IgE-Mediated Food Allergy.

Non-IgE-mediated food allergies are a group of disorders characterized by subacute or chronic inflammatory processes in the gut. Unlike IgE mediated food allergies that may result in multi-organ system anaphylaxis, the non-IgE mediated food allergies primarily affect the gastrointestinal tract. This review outlines the clinical manifestations, epidemiology, pathophysiology, and management of non-IgE-mediated food allergies. An updated literature search of selected non-IgE-mediated food allergies was conducted for this review using PubMed database to the current year (2021). Reviewed disorders include food protein-induced enterocolitis syndrome (FPIES), food-protein enteropathy (FPE), food protein-induced allergic proctocolitis (FPIAP), and eosinophilic gastrointestinal disorders (EGIDs) such as eosinophilic esophagitis (EoE). While extensive gains have been made in understanding FPIES, FPIAP, FPE, and EoE, more information is needed on the pathophysiology of these food allergies. Similarities among them include involvement of innate immunity, T-lymphocyte processes, alteration of the intestinal lumen at the cellular level with the appearance of inflammatory cells and associated histologic changes, and specific cytokine profiles suggesting food-specific, T-cell, and immune-mediated responses. While FPIES and FPIAP typically resolve in early childhood, EGIDs typically do not. Emerging new therapies for EoE offer promise of additional treatment options. Further studies identifying the immunopathogenesis, associated biomarkers, and mechanisms of tolerance are needed to inform prevention, diagnosis and management.

PROMIS-29 survey confirms major impact of fatigue on health-related quality of life in common variable immunodeficiency.

Health-related quality of life (HRQOL) is an emerging topic of interest in patients with immunodeficiency. Information about HRQOL in common variable immunodeficiency (CVID) is limited. The primary objective was to compare primary immunodeficiency disease (PIDD) patients with and without common variable immunodeficiency (CVID) on HRQOL domains using Patient-Reported Outcomes Measurement Information System (PROMIS-29) survey data from the United States Immunodeficiency Network (USIDNET) registry. The primary endpoint variables were scores on 7 HRQOL domains. The USIDNET registry was used to select patients with baseline PROMIS-29 data collected between 2015 and 2018. Descriptive statistics, Fisher's exact test, and Student's two-sample t test were used to compare patients with CVID versus patients with non-CVID on demographic and clinical characteristics. The single-sample t test was used to compare sample means to the normed population mean of 50. A general linear model approach to multiple regression with backward selection was used to remove factors that did not contribute significant information to the multivariable models, while controlling for multiple testing. Potential explanatory variables included group (CVID/non-CVID), sex, age, and BMI. Among 184 PIDD patients, 146 (79%) were diagnosed with CVID. Patients had a mean (SD) age of 53 (13.8), were predominantly female (83%), and were Caucasian (98%). PROMIS-29 results revealed a significant effect of group (CVID/non-CVID) on the anxiety, fatigue, and social participation domains, with fatigue being the most statistically significant. Fatigue, anxiety, and social participation may be key factors influencing HRQOL among patients with CVID. Future prospective longitudinal studies using PROMIS-29 will be needed to confirm these findings and to determine the mechanisms through which these factors develop in CVID, and how they can be improved.

Persons Living With Primary Immunodeficiency Act as Citizen Scientists and Launch Prospective Cohort Body Temperature Study.

BACKGROUND: Although fever is considered a sign of infection, many individuals with primary immunodeficiency (PI) anecdotally report a lower-than-normal average body temperature on online forums sponsored by the Immune Deficiency Foundation (IDF). There is limited knowledge about the average body temperature and fever response in PI. OBJECTIVE: This study aims to compare median body temperatures between adults with and without PI diagnoses living in the same household and to engage individuals living with PI throughout the research process. METHODS: Patients with PI designed and launched a prospective cohort comparison study as citizen scientists. A multidisciplinary team designed and implemented a patient-informed study with continuous patient-driven input. Median body temperatures were compared between the 2 cohorts using the Mann-Whitney test with Bonferroni correction. The IDF conducted a post-study patient experience survey. RESULTS: Data from 254 households were analyzed (254/350, 72.6% participation rate). The PI population was predominantly female (218/254, 85.8%), White (248/254, 97.6%), and with a median age of 49 years. The non-PI population was largely male (170/254, 66.9%), White (236/254, 92.9%), and with a median age of 53 years. Common variable immunodeficiency was the most common PI diagnosis (190/254, 74.8%). Of the 254 individuals with PI, 123 (48.4%) reported a lower-than-normal nonsick body temperature, whereas 108 (42.5%) reported a normal (between 97°F and 99°F) nonsick body temperature. Among individuals with PI, when infected, 67.7% (172/254) reported the absence of fever, whereas 19.7% (50/254) reported a normal fever response. The recorded median body temperature was minimally but statistically significantly higher for patients with PI in the morning. Although 22.4% (57/254) of patients with PI self-reported illness, a fever of 100.4°F or higher was uncommon; 77.2% (196/254) had a normal temperature (between 97°F and 99°F), and 16.2% (41/254) had a lower-than-normal temperature (between 95.0°F and 96.9°F) when sick. For these sick patients with PI, the median body temperature was minimally but statistically significantly higher for patients in the morning and early evening. Overall, 90.9% (231/254) of participants would be very likely to participate in future IDF studies, although 94.1% (239/254) participants had never taken part in previous studies. CONCLUSIONS: To our knowledge, this is the first study to evaluate average body temperature in individuals with PI. Although there were small statistically significant differences in body temperatures between PI and non-PI subjects, the clinical significance is unclear and should be interpreted with caution, given the methodological issues associated with our small convenience sample and study design. As PIs are heterogeneous, more research is needed about how the fever response differs among diverse PIs compared with healthy controls. This study highlights that individuals with PI are knowledgeable about their health and can offer unique insights and direction to researchers and clinicians.

Epidemiological trends among preterm infants with apnea. A twelve-year database review.

OBJECTIVES: This study sought to characterize trends in the diagnosis of apnea, associated comorbidities and complications, and 30-day readmission rates in preterm singleton infants. SUBJECTS AND METHODS: The study design was a retrospective, longitudinal, observational study. 2003-2014 New York State Statewide Planning and Research Cooperative System and New York City Vital Statistics databases were merged identifying preterm live singleton births. Hospitalizations of preterm newborns with and without apnea were compared; multivariable logistic regression and log-linear Poisson regression models applied. RESULTS: Of 1,384,013 singleton births, 7.5% were identified as preterm. While relative risk of preterm birth rates declined (RR = 0.987, 95% CI = 0.982-0.991), the diagnosis of apnea increased significantly (RR = 1.069, 95% CI = 1.049-1.089). Multivariable analysis identified two apnea predictors, gastric reflux (OR = 3.19, 95% CI = 2.80-3.63) and early gestational age (OR = 0.83 for 1 week GA increase, 95% CI = 0.82-0.84). Preterm newborns with apnea were more likely to be readmitted within the first 30 days and total charges were 5.4 times higher. CONCLUSIONS: While the preterm birth rate has declined the rate of diagnosis of apnea with associated comorbidities and complications has increased. Given the additional findings of higher 30-day readmission rates and charges, more multidisciplinary research appears warranted to identify ways to optimize the quality of high risk newborn care.

Temporal synchrony and audiovisual integration of speech and object stimuli in autism.

BACKGROUND: Individuals with Autism Spectrum Disorders (ASD) have been shown to have multisensory integration deficits, which may lead to problems perceiving complex, multisensory environments. For example, understanding audiovisual speech requires integration of visual information from the lips and face with auditory information from the voice, and audiovisual speech integration deficits can lead to impaired understanding and comprehension. While there is strong evidence for an audiovisual speech integration impairment in ASD, it is unclear whether this impairment is due to low level perceptual processes that affect all types of audiovisual integration or if it is specific to speech processing. METHOD: Here, we measure audiovisual integration of basic speech (i.e., consonant-vowel utterances) and object stimuli (i.e., a bouncing ball) in adolescents with ASD and well-matched controls. We calculate a temporal window of integration (TWI) using each individual's ability to identify which of two videos (one temporally aligned and one misaligned) matches auditory stimuli. The TWI measures tolerance for temporal asynchrony between the auditory and visual streams, and is an important feature of audiovisual perception. RESULTS: While controls showed similar tolerance of asynchrony for the simple speech and object stimuli, individuals with ASD did not. Specifically, individuals with ASD showed less tolerance of asynchrony for speech stimuli compared to object stimuli. In individuals with ASD, decreased tolerance for asynchrony in speech stimuli was associated with higher ratings of autism symptom severity. CONCLUSIONS: These results suggest that audiovisual perception in ASD may vary for speech and object stimuli beyond what can be accounted for by stimulus complexity.