Martin H. Bluth

Introduction: Early HIV replication in the gastrointestinal tract plays an important role in HIV pathogenesis. We have followed the onset of the acquired immune deficiency disease (AIDS) pandemic and human immunodeficiency virus (HIV) infection from its recognition in the US. Patients and Methods: We followed 34 adult HIV positive Veterans on cART comparing colon Innate Immune System (InImS) expression of a Paneth cell product (p87; the denominator) and blood ferritin (the numerator) to derive the FERAD ratio, and p87 expression by immunohistochemistry available in some of our HIV patients and compare the expression to 2252 without HIV. Stool and colonoscopically obtained tissue specimens were run in a p87 ELISA and immunohistochemistry for both fixed and native antigens, using the Adnab-9 antibody. Results: There were no significant differences in demographics aside from lower BMI in HIV patients (24.93 ± 6.30 vs. 28.0 ± 6.13 kg/m²) p < 0.0001. Native p87 antigen was elevated in HIV patients compared to controls in the ascending, transverse, and descending colon (0.794 ± 0.890 vs. 0.170 ± 0.201 respectively; p < 0.000004; 1.062 ± 0.730 vs. 0.202 ± 0.377 respectively; p < 0.000003; and 0.611 ± 0.182 vs. 0.174 ± 0.251 respectively; p < 0.0009), respectively; and Helicobacter pylori (H. pylori) detection was higher in HIV patients (84.6% vs. 36%; p < 0.0002). We also ran these assays in cancer patients for comparison. Conclusions: Colonic inflammation as expressed by p87, a Paneth cell product, is significantly elevated in HIV patients and likely represents continued HIV activity leading to inflammation.

Introduction: We have followed the onset of the acquired immune deficiency disease (AIDS) pandemic and human immunodeficiency virus (HIV) infection from its recognition in the US since 1981 (1) describing the disease’s impact on T-lymphocytes (2), leading to pulmonary and renal diseases, cancer (3) and fibrosis (4). The development of an effective therapeutic combination anti-retroviral therapy (cART) has revolutionized HIV’s impact globally and HIV infection is now regarded as a chronic disease. A major inflammatory component for chronic HIV is the gastrointestinal tract (GIT) which is a major site for HIV replication and persistence (5). However, few tools are currently available to assess the innate immune system (InImS) in HIV patients. In this study, we present data on InImS biomarkers in patients on cART showing that inflammation predicts mortality (1). Patients and Methods: From patients enrolled in a colorectal neoplasia prediction study (6) we followed 34 adult HIV positive Veterans on cART comparing colon InImS expression of a Paneth cell product, p87; the denominator) and blood ferritin (the numerator) to derive the FERAD ratio, and p87 expression by immunohistochemistry available in some of our HIV patients, and compare expression to 2,252 without HIV. Stool and colonoscopically-obtained tissue specimens were run in a p87 ELISA and immunohistochemistry for both fixed and native antigens, using the Adnab-9 antibody. Results: There were no significant differences in demographics aside from lower BMI in HIV patients (24.93±6.30 versus 28.0±6.13 kg/m2) p< 0.0001. HIV patients also had lower serum creatinine (0.99±0.23 versus 1.28±1.89; p< 0.0001) and were heavier smokers 88.9% vs 43.7% (OR 10.29[CI1.28-82.77];p< 0.008) and more frequent alcohol drinkers 71.4% vs 25.1% (OR 6.0 [CI1.7-20.9]) than controls. Native p87 antigen was elevated in HIV patients compared to controls in the ascending, transverse and descending colon (0.794±0.890 versus 0.170±0.201 respectively; p< 0.000004; 1.062±0.730 versus 0.202±0.377 respectively; p< 0.000003; and 0.611±0.182 versus 0.174±0.251 respectively; p< 0.0009), respectively; and Helicobacter pylori (H. pylori) detection was higher in HIV patients (84.6% versus 36%;p< 0.0002). We also ran these assays in cancer patients, for comparison. Conclusions: Colonic inflammation as expressed by p87, a Paneth cell product is significantly elevated in HIV patients and likely represents continued HIV activity leading to inflammation. Increased rates of smoking and drinking alcohol further contribute to inflammation, but there may be an ability to reduce p87 expression by intervention with folates (7) and manipulation of the abnormal HIV patient microbiome (8) may be effective therapies that warrant further study.

Secondary hemophagocytic lymphohistiocytosis (sHLH) is a severe hyperinflammatory syndrome characterized by excessive activation of the immune system, leading to multiorgan dysfunction and high mortality. This review explores the relationship between body mass index (BMI) and the risk of sHLH in leukemia patients living with human immunodeficiency virus (HIV). In this population, the compounded effects of immunosuppression and inflammatory conditions present unique challenges, making it crucial to understand the role of BMI in modulating these risks. Leukemia and HIV independently contribute to significant immune system dysregulation. When these conditions coexist, patients face increased susceptibility to infections and inflammatory disorders. BMI, an indicator of nutritional and metabolic status, can further influence immune responses. Low BMI, often associated with malnutrition, impairs immune function, while high BMI, linked to obesity, promotes chronic inflammation. Both extremes can exacerbate the cytokine storm characteristic of sHLH, leading to more severe clinical outcomes. Regular monitoring and addressing nutritional status through tailored interventions can potentially mitigate the risk of sHLH. A multidisciplinary approach, integrating the expertise of oncologists, infectious disease specialists, nutritionists, and immunologists, is essential for optimizing patient care and improving outcomes in this vulnerable population. Further research is necessary to deepen our understanding of the mechanisms linking BMI to sHLH and to develop evidence-based guidelines for clinical practice.

Sickle cell anemia (SCA) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin, leading to the formation of sickle-shaped red blood cells. While much research has focused on the molecular and cellular mechanisms underlying the pathophysiology of SCA, recent attention has turned to the role of apoptosis, or programmed cell death, in the disease progression. This review aims to elucidate the intricate mechanisms of apoptosis in SCA patients and explore its implications in disease severity, complications, and potential therapeutic interventions. Different research search engines such as PubMed central, Scopus, Web of Science, Google Scholar, ResearchGate, Academia Edu, etc were utilized in writing this paper. Apoptosis, a highly regulated cellular process, plays a crucial role in maintaining homeostasis by eliminating damaged or dysfunctional cells. In SCA, the imbalance between pro-apoptotic and anti-apoptotic signals contributes to increased erythrocyte apoptosis, exacerbating anemia and vaso-occlusive crises. Various factors, including oxidative stress, inflammation, and altered cell signaling pathways, converge to modulate the apoptotic response in SCA. Furthermore, the interaction between apoptotic cells and the vascular endothelium contributes to endothelial dysfunction, promoting the pathogenesis of vasculopathy and organ damage seen in SCA patients. In conclusion, unraveling the complexities of apoptosis in SCA provides valuable insights into the disease pathophysiology and offers novel avenues for therapeutic interventions.

Purpose: Children with cancer and survivors frequently report posttraumatic stress symptoms (PTSS), which are associated with volumetric changes in stress-sensitive brain regions, including the hippocampus. Methods: We examined the impact of a novel, 4-week martial-arts-based meditative intervention on cancer-related PTSS in 18 pediatric patients and survivors and whether baseline hippocampal volumes correlate with PTSS severity and/or PTSS changes over time. Results: Overall, PTSS did not significantly change from baseline to post-intervention. Smaller hippocampal volume was correlated with more severe re-experiencing PTSS at baseline, and greater reductions in PTSS post-intervention. Conclusions: Together, hippocampal volume may be a biomarker of PTSS severity and intervention response. Identifying hippocampal volume as a potential biomarker for PTSS severity and intervention response may allow for more informed psychosocial treatments.

SARS-CoV-2 severity predictions are feasible, though individual susceptibility is not. The latter prediction allows for planning vaccination strategies and the quarantine of vulnerable targets. Ironically, the innate immune response (InImS) is both an antiviral defense and the potential cause of adverse immune outcomes. The competition for iron has been recognized between both the immune system and invading pathogens and expressed in a ratio of ferritin divided by p87 (as defined by the Adnab-9 ELISA stool-binding optical density, minus the background), known as the FERAD ratio. Associations with the FERAD ratio may allow predictive modeling for the susceptibility and severity of disease. We evaluated other potential COVID-19 biomarkers prospectively. Patients with PCR+ COVID-19 tests (Group 1; n = 28) were compared to three other groups. In Group 2 (n = 36), and 13 patients displayed COVID-19-like symptoms but had negative PCR or negative antibody tests. Group 3 (n = 90) had no symptoms and were negative when routinely PCR-tested before medical procedures. Group 4 (n = 2129) comprised a pool of patients who had stool tests and symptoms, but their COVID-19 diagnoses were unknown; therefore, they were chosen to represent the general population. Twenty percent of the Group 4 patients (n = 432) had sufficient data to calculate their FERAD ratios, which were inversely correlated with the risk of COVID-19 in the future. In a case report of a neonate, we studied three biomarkers implicated in COVID-19, including p87, Src (cellular-p60-sarcoma antigen), and Abl (ABL-proto-oncogene 2). The InImS of the first two were positively correlated. An inverse correlation was found between ferritin and lysozyme in serum (p < 0.05), suggesting that iron could have impaired an important innate immune system anti-viral effector and could partially explain future COVID-19 susceptibility.

Background: We investigated the utility of an automated chemiluminescent SARS-CoV-2 IgG antibody assay platform in quantifying the amount of binding antibodies present in donated convalescent plasma. Methods: A total of 179 convalescent plasma units were analyzed for the presence of SARS-CoV-2 IgG antibodies using the Beckman-Coulter chemiluminescent immunoassay (CLIA) platform. The equipment-derived numerical values (S/Co ratio) were recorded. Aliquots from the same units were subjected to enzyme-linked immunosorbent assay (ELISA) that detects IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 S1 protein. The relationship between ELISA titers and CLIA S/Co values was analyzed using linear regression and receiver operating characteristics (ROC) curve. Results: Twenty-one samples (11.7%) had S/Co values of less than 1.0 and were deemed negative for antibodies and convalescent plasma had S/Co values between > 1.0 and 5.0 (70/179, 39.1%). Fifteen units (8.4%) had negative ELISA titer. The majority of the units (95/179. 53.1%) had titers ≥ 1:1024. The sensitivities of ELISA to CLIA were comparable (90.5% vs 88.3%, respectively; p=0.18). There was positive linear correlation between CLIA S/Co values and ELISA IgG titer (Rho = 0.75; Spearman’s rank = 0.82, p-value = < 0.0001). The agreement between the two methods was fair, with a κ index of 0.2741. Using the ROC analysis, we identified a CLIA S/Co cutoff value of 8.2, which gives a sensitivity of 90% and a specificity of 82% in predicting a titer dilution of ≥ 1:1024. Conclusion: The utility of automated antibody detection systems can be extended from simply a screening method to a semi-quantitative and quantitative functional antibody analysis. CLIA S/Co values can be used to reliably estimate the ELISA antibody titer. Incorporation of chemiluminescent-based methods can provide rapid, cost-effective means of identifying anti-SARS-CoV-2 antibody titers in donated plasma for use in the treatment of COVID-19 infection.