Small intestinal immunopathology and GI-associated antibody formation in hereditary alpha-tryptasemia.

BACKGROUND: Hereditary alpha-tryptasemia (HαT) is characterized by elevated basal serum tryptase due to increased copies of the TPSAB1 gene. Individuals with HαT frequently present with multisystem complaints, including anaphylaxis and seemingly functional gastrointestinal (GI) symptoms. OBJECTIVE: We sought to determine the prevalence of HαT in an irritable bowel syndrome cohort and associated immunologic characteristics that may distinguish patients with HαT from patients without HαT. METHODS: Tryptase genotyping by droplet digital PCR, flow cytometry, cytometry by time-of-flight, immunohistochemistry, and other molecular biology techniques was used. RESULTS: HαT prevalence in a large irritable bowel syndrome cohort was 5% (N = 8/158). Immunophenotyping of HαT PBMCs (N ≥ 27) revealed increased total and class-switched memory B cells. In the small bowel, expansion of tissue mast cells with expression of CD203c, HLA-DR, and FcεRI, higher intestinal epithelial cell pyroptosis, and increased class-switched memory B cells were observed. IgG profiles in sera from individuals with HαT (N = 21) significantly differed from those in individuals with quiescent Crohn disease (N = 20) and non-HαT controls (N = 19), with increased antibodies directed against GI-associated proteins identified in individuals with HαT. CONCLUSIONS: Increased mast cell number and intestinal epithelial cell pyroptosis in the small intestine, and class-switched memory B cells in both the gut and peripheral blood associated with IgG reactive to GI-related proteins, distinguish HαT from functional GI disease. These innate and adaptive immunologic findings identified in association with HαT are suggestive of subclinical intestinal inflammation in symptomatic individuals.

STRIDES - STudying Risk to Improve DisparitiES in Cervical Cancer in Mississippi - Design and baseline results of a Statewide Cohort Study.

Cervical cancer rates in Mississippi are disproportionately high, particularly among Black individuals; yet, research in this population is lacking. We designed a statewide, racially diverse cohort of individuals undergoing cervical screening in Mississippi. Here, we report the baseline findings from this study. We included individuals aged 21 years and older undergoing cervical screening with cytology or cytology-human papillomavirus (HPV) co-testing at the Mississippi State Health Department (MSDH) and the University of Mississippi Medical Center (UMMC) (December 2017-May 2020). We collected discarded cytology specimens for future biomarker testing. Demographics and clinical results were abstracted from electronic medical records and evaluated using descriptive statistics and chi-square tests. A total of 24,796 individuals were included, with a median age of 34.8 years. The distribution of race in our cohort was 60.2% Black, 26.4% White, 7.5% other, and 5.9% missing. Approximately 15% had abnormal cytology and, among those who underwent co-testing at MSDH (n = 6,377), HPV positivity was 17.4% and did not vary significantly by race. Among HPV positives, Black individuals were significantly less likely to be HPV16/18 positive and more likely to be positive for other high-risk 12 HPV types compared to White individuals (20.5% vs. 27.9%, and 79.5% and 72.1%, respectively, p = 0.011). Our statewide cohort represents one of the largest racially diverse studies of cervical screening in the U.S. We show a high burden of abnormal cytology and HPV positivity, with significant racial differences in HPV genotype prevalence. Future studies will evaluate cervical precancer risk, HPV genotyping, and novel biomarkers in this population.

Age-specific prevalence of human papillomavirus and abnormal cytology at baseline in a diverse statewide prospective cohort of individuals undergoing cervical cancer screening in Mississippi.

BACKGROUND: Mississippi (MS) has among the highest rates of cervical cancer incidence and mortality in the United States, with disproportionately higher rates among Blacks compared to Whites. Here, we evaluate the prevalence of high-risk human papillomavirus (HPV) and abnormal cytology in a representative baseline sample from a diverse statewide cohort of individuals attending cervical screening in MS from the STRIDES Study (STudying Risk to Improve DisparitiES in cervical cancer). METHODS: We included individuals aged 21-65 years undergoing screening at the University of Mississippi Medical Center (UMMC) and the Mississippi State Department of Health (MSDH) from May to November 2018. We calculated age-specific HPV prevalence, overall and by partial HPV16/18 genotyping, and abnormal cytology by race. RESULTS: A total of 6871 individuals (mean age 35.7 years) were included. HPV prevalence was 25.6% and higher in Blacks (28.0%) compared to Whites (22.4%). HPV prevalence was significantly higher in Blacks aged 21-24 years (50.2%) and 30-34 years (30.2%) compared to Whites in the same age groups (32.1% and 20.7%; p < 0.0001, respectively). The prevalence of high-grade cytologic abnormalities, a cytologic sign of cervical precancer, peaked earlier in Blacks (ages 25-29) compared to Whites (35-39). For comparison, we also analyzed HPV prevalence data from the National Health and Nutrition Examination Survey (NHANES, 2013-2016) and observed similar racial differences in HPV prevalence among women aged 21-24 years. CONCLUSIONS: Our findings suggest that Blacks undergoing cervical cancer screening in MS have higher prevalence of other high-risk 12 HPV types at younger ages and experience an earlier peak of high-grade cytologic abnormalities compared to Whites.

Fulminant hepatic failure attributed to ackee fruit ingestion in a patient with sickle cell trait.

We report a case of fulminant liver failure resulting in emergent liver transplantation following 3 weeks of nausea, vomiting, and malaise from Jamaican Vomiting Sickness. Jamaican Vomiting Sickness is caused by ingestion of the unripe arils of the Ackee fruit, its seeds and husks. It is characterized by acute gastrointestinal illness and hypoglycemia. In severe cases, central nervous system depression can occur. In previous studies, histologic sections taken from patients with Jamaican Vomiting Sickness have shown hepatotoxicity similar to that seen in Reye syndrome and/or acetaminophen toxicity. We highlight macroscopic and microscopic changes in the liver secondary to hepatoxicity of Ackee fruit versus those caused by a previously unknown sickle cell trait. We discuss the clinical variables and the synergistic hepatotoxic effect of Ackee fruit and ischemic injury from sickled red blood cells, causing massive hepatic necrosis in this patient.