Mouse Models of Food Allergy in the Pursuit of Novel Treatment Modalities

The prevalence of IgE-mediated food allergies has increased dramatically in the past three decades, now affecting up to 10% of the US population. IgE-mediated food allergy is an immunologic disease, involving a variety of cells, including B and T cells, mast cells, basophils, ILC2s, and epithelial cells. Mouse models of food allergy mimic the overall immunologic processes known to exist in humans. Due to the limitations of invasive sampling of human tissue and the similarities of the human and mouse immune systems, comprehensive pathogenesis studies of food allergy have been performed in mouse models. Mouse models have been effective in elucidating the roles of non-oral routes of sensitization and identifying key cells and molecules involved in allergic sensitization. Furthermore, the development of novel therapeutic approaches for food allergy has been accelerated through the use of pre-clinical mouse models. Despite the groundbreaking findings stemming from research in mice, there are continued efforts to improve the translational utility of these models. Here, we highlight the achievements in understanding food allergy development and efforts to bring novel treatment approaches into clinical trials.

State-of-the-Art Review of Pregnancy-Related Psoriasis

Psoriasis is a chronic immunologic disease involving inflammation that can target internal organs, the skin, and joints. The peak incidence occurs between the age of 30 and 40 years, which overlaps with the typical reproductive period of women. Because of comorbidities that can accompany psoriasis, including metabolic syndrome, cardiovascular involvement, and major depressive disorders, the condition is a complex one. The role of hormones during pregnancy in the lesion dynamics of psoriasis is unclear, and it is important to resolve the implications of this pathology during pregnancy are. Furthermore, treating pregnant women who have psoriasis represents a challenge as most drugs generally prescribed for this pathology are contraindicated in pregnancy because of teratogenic effects. This review covers the state of the art in psoriasis associated with pregnancy. Careful pregnancy monitoring in moderate-to-severe psoriasis vulgaris is required given the high risk of related complications in pregnancy, including pregnancy-induced hypertensive disorders, low birth weight for gestational age, and gestational diabetes. Topical corticosteroids are safe during pregnancy but effective only for localised forms of psoriasis. Monoclonal antibodies targeting cytokines specifically upregulated in psoriasis, such as ustekinumab (IL-12/23 inhibitor), secukinumab (IL-17 inhibitor) can be effective for the severe form of psoriasis during pregnancy. A multidisciplinary team must choose optimal treatment, taking into account fetal and maternal risks and benefits.

A Primer on the Clinical Aspects of Sarcoidosis for the Basic and Translational Scientist

The immunopathogenesis of sarcoidosis remains unclear. This failure in understanding has been clinically impactful, as it has impeded the accurate diagnosis, treatment, and prevention of this disease. Unraveling the mechanisms of sarcoidosis will require input from basic and translational scientists. In order to reach this goal, scientists must have a firm grasp of the clinical aspects of the disease, including its diagnostic criteria, the immunologic defects, clinical presentations, response to therapy, risk factors, and clinical course. This manuscript will provide an overview of the clinical aspects of sarcoidosis that are particularly relevant for the basic and translational scientist. The variable phenotypic expression of the disease will be described, which may be integral in identifying immunologic disease mechanisms that may be relevant to subgroups of sarcoidosis patients. Data concerning treatment and risk factors may yield important insights concerning germane immunologic pathways involved in the development of disease. It is hoped that this manuscript will stimulate communication between scientists and clinicians that will eventually lead to improved care of sarcoidosis patients.

Glycans in Immunologic Health and Disease

The surfaces of all living organisms and most secreted proteins share a common feature: They are glycosylated. As the outermost-facing molecules, glycans participate in nearly all immunological processes, including driving host-pathogen interactions, immunological recognition and activation, and differentiation between self and nonself through a complex array of pathways and mechanisms. These fundamental immunologic roles are further cast into sharp relief in inflammatory, autoimmune, and cancer disease states in which immune regulation goes awry. Here, we review the broad impact of glycans on the immune system and discuss the changes and clinical opportunities associated with the onset of immunologic disease. Expected final online publication date for the Annual Review of Immunology, Volume 39 is April 2021. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

Late-onset and long-lasting autoimmune neutropenia: an analysis from the Italian Neutropenia Registry

Primary autoimmune neutropenia (pAN) is typified by onset in early infancy and a mild/moderate phenotype that resolves within 3 years of diagnosis. In contrast, secondary AN is classically an adult disease associated with malignancy, autoimmunity, immunodeficiency, viral infection, or drugs. This study describes a cohort of 79 children from the Italian Registry who, although resembling pAN, did not fully match the criteria for pAN because neutropenia either appeared after age 5 years (LO-Np) or lasted longer than 3 years (LL-Np). These 2 categories compared with classical pAN showed a far inferior rate of resolution (P < .001), lower severity of neutropenia (P = .03), leukopenia (P < .001), lymphopenia (P < .001) with low B+ (P = .001), increased need of granulocyte colony-stimulating factor (P = .04), and increased frequency of autoimmunity over the disease course (P < .001). A paired comparison between LO-Np and LL-Np suggested that LO-Np had a lower rate of resolution (P < .001) and lower white blood cell (P < .001) and lymphocyte (P < .001) values, higher occurrence of apthae (P = .008), and a stronger association with autoimmune diseases/markers (P = .001) than LL-Np, thus suggesting a more pronounced autoimmune signature for LO-Np. A next-generation sequencing panel applied in a small subgroup of LO-Np and LL-Np patients identified variants related to immune dysregulations. Overall, these findings indicate that there are important differences among pAN LL-Np and LO-Np. Forms rising after 3 years of age, with low tendency to resolution, require tight monitoring and extensive immune investigations aimed to early identify underlying immunologic disease.

Abstract 12852: Cardioembolic Myocardial Infarction in the Setting of Complex Immunologic Disease

Background: The occurrence of left atrial appendage (LAA) thrombus formation and embolic myocardial infarction (MI) is rarely reported in the absence of atrial fibrillation (AF). In patients with a history of immunologic disease, a multidisciplinary approach is critical for prompt evaluation and treatment. Presentation: A 46-year-old woman with chest pain and lower extremity paresthesias was found to have NSTEMI. Past medical history was notable for vasculitis and multiple organ infarcts. Coronary angiogram and cardiac MRI showed no obstructive or structural disease. One month later she had recurrent chest pain with inferior ST-elevations on ECG and troponin of 24ng/mL. Investigations and Outcome: Coronary catheterization showed multiple embolic occlusions (Figure 1A and 1B). Subsequent TEE showed LAA thrombus (Figure 1C). Continuous telemetry and serial ECGs from initial presentation were negative for AF. Hypercoagulable and antiphospholipid testing was negative. Brain MRI for paresthesias showed dural enhancement and subsequent biopsy found an IgG4 inflammatory process. Treatment with warfarin, corticosteroids, and rituximab was initiated. No atrial fibrillation was detected on serial EKGs and an event monitor during one year of follow-up. There was no embolic recurrence. Conclusion: Autoimmune diseases can have complex organ involvement through lesser known mechanisms which often present as diagnostic challenges. This case identifies the potential for cardioembolic events, including myocardial infarction, in IgG4 vasculitis even in the absence of atrial fibrillation or hypercoagulability.

Older age at infection and nulliparity are associated with long-term non-progression in female sex workers infected with non-subtype B HIV-1

Studies have reported on HIV-infected, antiretroviral therapy (ART)-naïve individuals who show minimal disease progression despite prolonged infection. The characteristics of these long-term non-progressors (LTNPs) are not well-characterized in populations predominantly infected with non-subtype B HIV-1. Female sex workers in Mombasa, Kenya who acquired HIV-1 were studied to ascertain immunologic disease progression. Long-term non-progression was defined as an ART-naïve duration of infection ≥7 years and a majority of CD4+ cell counts ≥600 cells/µl with a non-declining CD4+ trend. Correlates of long-term non-progression were determined using multivariable logistic regression. Between February 1993 and March 2014, 332 women acquired HIV-1. Of these, 77 (23%) had ≥7 years of follow-up and 13 (17%) were categorized as LTNPs. Factors associated with long-term non-progression included age >30 years at infection (aOR = 9.41, 95% CI: 1.48–59.86, P = 0.005) and nulliparity (aOR = 20.19, 95% CI: 1.36–299.90, P = 0.03). Each log10 copies/ml increase in viral load (VL) set point was associated with a lower likelihood of being a LTNP (aOR = 0.31, 95% CI: 0.12–0.79, P = 0.01). These findings suggest that age and parity may influence the likelihood of long-term non-progression through mechanisms that are not mediated by the effects of these variables on VL. Future studies should seek to determine whether the associations presented are reproducible.

Recognizing the Effect of Ecosystem Disruption on Human Health and Neurodevelopment

The topics of climate change and ecosystem disruption are at the forefront of global discussion. Accordingly, there is a sense of urgency among citizens, environmental experts, and political leaders for action and policy change. While the effect of a changing climate on the environment is well recognized, its impact on the human body has not been sufficiently described. In our review, we will attempt to outline some of these effects. We will discuss how the recent surge of immunologic disease may be related to the changing profile of microorganisms and antigens in our every-day environment. We will explore how the introduction of antibiotics may result in an altered gut microbiome, and subsequently abnormal neurodevelopment. Finally, we will discuss a possible link between chemical preservatives and neoplastic disease.

Mandibular Osteomyelitis in Concurrence with Psoriasis: A Rare Case Report and Literature Review

Mandibular osteomyelitis in a patient with psoriasis is an uncommonly clinical manifestation while there is an increasing number of reports and studies on involvements of stomatology in psoriasis, especially the death of a patient via or not via Allogeneic bone marrow transplantation has never been reported. To review the management and possible mechanisms in pathogenesis and treatment of psoriasis, as well as the relative involvements between stomatology and psoriasis the typical case with pictures and files is reviewed and literature is collected.Wekeepthe knowledge that psoriasis is either a primary keratinocyte disorder or an immunocyte-mediated chronic skin inflammatory disease while bone marrow is under suspected for immunopathogenesis. More association of stomatologic conditions with psoriasis is emerging. Conclusively, allogeneic BMT and new knowledge are worth to be stressed by both stomatological and dermatological doctors. Further insights of this kind of auto immunologic disease are under its developing.

Gene Expression Differences in Host Response to Schistosoma haematobium Infection

ABSTRACT Schistosome worms infect over 200 million people worldwide. They live in the host’s bloodstream and alter host immunity. Epidemiological data suggest that males and females have different responses to schistosome infection, but the effect of sex on systemic response is undetermined. Our objective was to characterize differences in peripheral blood transcriptional profiles in people with or without active Schistosoma haematobium infection and to determine whether this signature differs between males and females. mRNA was isolated using poly(A) selection and sequenced on an Illumina Hi-Seq4000 platform. Transcripts were aligned to the human hg19 reference genome and counted with the HTSeq package. Genes were compared for differential expression using DESeq2. Ingenuity Pathway Analysis (IPA) was used to identify gene networks altered in the presence of S. haematobium. We enrolled 33 participants from villages in rural Tanzania where S. haematobium is endemic. After correction for multiple comparisons, we observed 383 differentially expressed genes between those with or without S. haematobium infection when sex was included as a covariate. Heat-mapping of the genes with >1.5-fold differences in gene expression revealed clustering by S. haematobium infection status. The top networks included development, cell death and survival, cell signaling, and immunologic disease pathways. We observed a distinct whole blood transcriptional profile, as well as differences in men and women, with S. haematobium infection. Additional studies are needed to determine the clinical effects of these divergent responses. Attention to sex-based differences should be included in studies of human schistosome infection.