Jelena Eremija

Interests

No activities entered.

Courses

No activities entered.

Scholarly Contributions

Journals/Publications

• Eremija, J., Eremija, J., Carr, T., & Carr, T. (2023). New Evidence on the Development of Atopic Multimorbidity: Are Patients Marching to the Beat of Their Own Drum?. Journal of Allergy and Clinical Immunology: In Practice, 11(8). doi:10.1016/j.jaip.2023.05.032
• Eremija, J., Patel, S., Rice, S., & Daines, M. (2023). Intravenous immunoglobulin treatment improves multiple neuropsychiatric outcomes in patients with pediatric acute-onset neuropsychiatric syndrome. Frontiers in Pediatrics, 11. doi:10.3389/fped.2023.1229150
  More info

  Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) is defined by acute onset of diverse neuropsychiatric manifestations, presumably in the setting of underlying immune dysfunction. We used standardized neuropsychological testing to assess how intravenous immunoglobulins (IVIG) impact neurological and cognitive functions in PANS patients by comparing pretreatment with post-treatment scores. A 5-year retrospective study was undertaken in Children's Postinfectious Autoimmune Encephalopathy Center at University of Arizona. We identified 12 children diagnosed with PANS and treated with immunomodulatory IVIG doses, who also completed neuropsychological testing before and after treatment. We tracked multiple patient characteristics, type/timeline of testing, and number of IVIG courses. Score change of 1 standard deviation in any tested domain/subdomain was considered improvement. We further reviewed records for laboratory signs of triggering infection and immune dysfunction. Improvement occurred in 11/12 patients, in one or multiple domains/subdomains, independently of time between disease onset and IVIG initiation (0–7 years). Participants received 1–7 IVIG courses. Improvement was primarily seen in memory (58%), sensory-motor (37%) and visual-motor integration (30%). In 5/12 patients we detected hypogammaglobulinemia requiring ongoing IVIG replacement, one patient had isolated low IgA. Only one patient had to discontinue IVIG therapy due to severe adverse effects. Standardized neuropsychological testing represents an important tool to objectively measure improvement in PANS patients. IVIG was tolerated well and showed efficacy in the vast majority of participants, independently from timelapse since disease onset, emphasizing impact of immunomodulation in PANS. Significant presence of baseline hypogammaglobulinemia in children with PANS emphasizes the presumed role of immune dysfunction in disease pathogenesis.
• Eremija, J., & Carr, T. (2022). Immunotherapy for Asthma. Seminars in Respiratory and Critical Care Medicine, 43(5). doi:10.1055/s-0042-1749454
  More info

  Asthma represents one of the biggest global health concerns with increasing prevalence and influence on global health. Several distinct asthma phenotypes have been identified with one of the most common, earliest recognized, and described being the allergic asthma phenotype, in which allergens trigger asthma through mechanisms involving allergen-specific immunoglobulin E (IgE). Allergen-specific immunotherapy (AIT), in the forms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT), has been used for many decades as a tool for reducing IgE-mediated sensitization and controlling symptoms of allergic disease, most commonly for allergic rhinitis, and it remains the only currently available disease modifying therapy in atopic patients. AIT has been studied for use in mild to moderate allergic asthma. While the data are often inconsistent, and utilize a multitude of different methods, antigens, and outcome measures, in general, AIT may have several beneficial effects on asthma disease control, quality of life, and requirement for medication. These benefits are notable when immunotherapy is used as an adjunct to pharmacologic treatment in carefully selected and monitored patients with mild to moderate persistent asthma. Patients with severe asthma are excluded from these trials. Importantly, patients with asthma, and in particular severe asthma, may have a higher rate of systemic adverse reactions to SCIT, including anaphylaxis; however, these events are overall rare. Future research in the area is needed to definitively assess the benefit of SCIT and SLIT for patients with asthma, comparing outcomes with different methods, addressing the role of AIT in severe asthma, significance of multiallergen AIT in allergic asthma, and safety concerns in asthma.
• Molina, M., Stokes, J., Hoffman, E., Eremija, J., Zeng, Y., Simpson, R., & Katsanis, E. (2020). Bendamustine Conditioning Skews Murine Host DCs Toward Pre-cDC1s and Reduces GvHD Independently of Batf3. Frontiers in Immunology, 11. doi:10.3389/fimmu.2020.01410
  More info

  Graft-versus-host disease (GvHD) remains the second leading cause of death in allogeneic hematopoietic stem cell transplantation recipients, highlighting the need for improved preventative strategies. Our laboratory has previously demonstrated in an experimental bone marrow transplantation (BMT) model that bendamustine combined with total body irradiation (BEN+TBI) is a safer alternative to cyclophosphamide with TBI (CY+TBI). The biological mechanisms of action of BEN have not been fully elucidated and likely involve multiple cell populations. Host dendritic cells (DCs) can prime naïve donor T-cells immediately following transplantation, making host DCs critical for the initiation phase of GvHD. We hypothesized that BEN+TBI conditioning favorably alters host DC composition to reduce GvHD. We demonstrate that host DCs treated with BEN+TBI induce less allogeneic T-cell proliferation than those conditioned with CY+TBI. We further show that BEN+TBI conditioning results in greater total numbers of all host DC subsets but with a more favorable composition compared to CY+TBI with significantly larger proportions of type 1 conventional DCs (cDC1), a highly regulatory DC subset capable of suppressing GvHD. Our studies using recipient Batf3 KO mice indicate that CD8α+ cDC1s are largely dispensable for the reduced GvHD following BEN+TBI conditioning. We found a higher frequency of host pre-cDC1s with BEN+TBI conditioning in both wild-type (WT) and Batf3 KO mice, which was inversely associated with GvHD. Additionally, we observed that BEN treatment results in greater expression of Flt3 receptor (CD135) on host DCs compared to CY, potentially contributing to the skewing of host DCs toward cDC1s. Further, BEN+TBI conditioning results in host cDCs with greater expression of PIR-B, an inhibitory receptor capable of preventing lethal GvHD. We conclude that BEN+TBI is a safer alternative to CY+TBI, resulting in a greater frequency of host pre-cDC1s and limiting GvHD.
• Stokes, J., Hoffman, E., Molina, M., Eremija, J., Larmonier, N., Zeng, Y., & Katsanis, E. (2019). Bendamustine with Total Body Irradiation Limits Murine Graft-versus-Host Disease in Part Through Effects on Myeloid-Derived Suppressor Cells. Biology of Blood and Marrow Transplantation, 25(3). doi:10.1016/j.bbmt.2018.10.009
  More info

  Graft-versus-host disease (GVHD) remains a significant challenge in allogeneic hematopoietic cell transplantation (HCT). An underinvestigated strategy to reduce GVHD is the modification of the preparative conditioning regimen. In the present study, we aimed to evaluate GVHD associated with bendamustine (BEN) conditioning in conjunction with total body irradiation (TBI) as an alternative to the standard myeloablative regimen of cyclophosphamide (CY) and TBI. We demonstrate that BEN-TBI conditioning, although facilitating complete donor chimerism, results in significantly less GVHD compared with CY-TBI. In BEN-TBI-conditioned mice, suppressive CD11b + Gr-1 high myeloid cells are increased in the blood, bone marrow, spleen, and intestines. When Gr-1 high cells are depleted before transplantation, the beneficial effects of BEN-TBI are partially lost. Alternatively, administration of granulocyte colony-stimulating factor, which promotes CD11b + Gr-1 + myeloid cell expansion, is associated with a trend toward increased survival in BEN-TBI-conditioned mice. These findings indicate a potential role of myeloid-derived suppressor cells in the mechanism by which BEN allows engraftment with reduced GVHD. BEN-TBI conditioning may present a safer alternative to CY-TBI conditioning for allogeneic HCT.
• Molina, M. S., Stokes, J., Hoffman, E. A., Eremija, J., Zeng, Y. X., & Katsanis, E. (2018). Bendamustine Conditioning Induces Phenotypic and Functional Changes in Host Antigen-Presenting Cells Which May Confer Protection Against GvHD. The Journal of Immunology, 200(1_Supplement), 55.17-55.17. doi:10.4049/jimmunol.200.supp.55.17
• , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , ., , , ., et al. (2014). International Nosocomial Infection Control Consortiu (INICC) report, data summary of 43 countries for 2007-2012. Device-associated module. American Journal of Infection Control, 42(9). doi:10.1016/j.ajic.2014.05.029
  More info

  We report the results of an International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2007-December 2012 in 503 intensive care units (ICUs) in Latin America, Asia, Africa, and Europe. During the 6-year study using the Centers for Disease Control and Prevention's (CDC) U.S. National Healthcare Safety Network (NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 605,310 patients hospitalized in the INICC's ICUs for an aggregate of 3,338,396 days. Although device utilization in the INICC's ICUs was similar to that reported from ICUs in the U.S. in the CDC's NHSN, rates of device-associated nosocomial infection were higher in the ICUs of the INICC hospitals: the pooled rate of central line-associated bloodstream infection in the INICC's ICUs, 4.9 per 1,000 central line days, is nearly 5-fold higher than the 0.9 per 1,000 central line days reported from comparable U.S. ICUs. The overall rate of ventilator-associated pneumonia was also higher (16.8 vs 1.1 per 1,000 ventilator days) as was the rate of catheter-associated urinary tract infection (5.5 vs 1.3 per 1,000 catheter days). Frequencies of resistance of Pseudomonas isolates to amikacin (42.8% vs 10%) and imipenem (42.4% vs 26.1%) and Klebsiella pneumoniae isolates to ceftazidime (71.2% vs 28.8%) and imipenem (19.6% vs 12.8%) were also higher in the INICC's ICUs compared with the ICUs of the CDC's NHSN.
• Eremija, J., Milenković, T., Mitrović, K., Plavšić, L., Todorović, S., & Vuković, R. (2014). The first case of papillary thyroid carcinoma in an adolescent with congenital dyshormonogenetic hypothyroidism in Serbia. Vojnosanitetski Pregled, 71(11). doi:10.2298/VSP1411078E
  More info

  Introduction. Differentiated thyroid carcinoma (DTC) is a rare childhood malignancy, as it represents 0.3-0.4% of pediatric malignancies. Papillary carcinoma is the most common type of pediatric DTC and it represents about 90% of all DTC patients. Although rare, DTC arising from dyshormonogenetic goiter is the most serious complication of congenital hypothyroidism. Case report. We presented the development of thyroid papillary carcinoma in a 15-year-old girl diagnosed with congenital dyshormonogenetic hypothyroidism at neonatal age. Considering the early initiation and proper dosage of hormonal substitution, normal levels of thyreotropin and thyroid hormones were achieved quickly and maintained through a follow-up period. The girl remained euthyroid and asymptomatic until 13.8 years of age, when she presented with a large multinodular goiter. The patient underwent total thyroidectomy. Pathological examination revealed intrathyroid microcarcinoma in the right lobe. Conclusion. Although differentiated thyroid carcinoma is a rare pediatric malignancy, it is of great importance to have a certain degree of clinical caution and provide a multidisciplinary approach during the follow-up of patients with dyshormonogenetic hypothyroidism.

Poster Presentations

• Eremija, J., & Daines, M. O. (2023, spring). Neuropsychiatric Testing Provides Objective Insight Into Beneficial Effects Of Intravenous Immunoglobulins In Patients With Pediatric Acute-Onset Neuropsychiatric Syndrome. AAAAI.
  More info

  poster presentation
• Eremija, J. (2022, fall). Rare Cutaneous Adverse Reaction to Routine Immunizations Leading to Hyper IgE Syndrome (HIES) Diagnosis. ACAAI 2022.
• Eremija, J. (2022, fall). SARS-CoV-2 Infection associated with new severe hypereosinophilia and multiple organ damage. ACAAI 2022.