Evan Maestri

All Publications

• Viral antibody response predicts morbidity and mortality in alcohol-associated hepatitis. Hepatology (Baltimore, Md.) Hsu, C. L., Wang, L., Maestri, E., Jacob, A. R., Do, W. L., Mayo, S., Bosques-Padilla, F., Verna, E. C., Abraldes, J. G., Brown, R. S., Vargas, V., Altamirano, J., Caballería, J., Shawcross, D. L., Louvet, A., Lucey, M. R., Mathurin, P., Garcia-Tsao, G., Stärkel, P., Bataller, R., Investigators, A., Wang, X. W., Schnabl, B. 2024

  Abstract

  Alcohol-associated hepatitis (AH) is associated with very high mortality despite abstinence from alcohol; up to 40% of patients die within 6 months of diagnosis. Patients with AH are especially prone to infections, which can lead to multiorgan dysfunction and poorer prognosis.We performed comprehensive serological profiling of the viral and bacterial infection history of 36 healthy controls, 48 patients with alcohol use disorder, and 224 patients with AH from 2 multicenter observational studies. We used systematic viral and bacterial epitope scanning by VirScan, a phage-display immunoprecipitation and sequencing technology that detects the peptides recognized by antibodies in patient sera, to comprehensively analyze antiviral and antibacterial antibodies and identify serologic biomarkers to predict patient outcomes. We found significant differences in the serological profiles of the 3 populations. The number of serum antibody epitopes in patients with alcohol use disorder during abstinence was increased compared with during active alcohol use. A decreased number and diversity of viral and bacterial antibody targets were detected in the sera of patients with AH, particularly those with a higher Child-Pugh score. In patients with AH, a decrease in the serum antiviral, but not antibacterial, antibody repertoire was associated with decompensation and mortality. Ninety-day mortality in AH could be predicted using a serum viral epitope signature.Abstinence from alcohol is associated with a significant increase in serum viral and bacterial antibody response. Decreased serum antiviral antibody repertoire is predictive of decompensation of liver disease and mortality in patients with AH.

  View details for DOI 10.1097/HEP.0000000000001046

  View details for PubMedID 39325984

• Spatial proximity of tumor-immune interactions predicts patient outcome in hepatocellular carcinoma. Hepatology (Baltimore, Md.) Maestri, E., Kedei, N., Khatib, S., Forgues, M., Ylaya, K., Hewitt, S. M., Wang, L., Chaisaingmongkol, J., Ruchirawat, M., Ma, L., Wang, X. W. 2024; 79 (4): 768-779

  Abstract

  The fitness and viability of a tumor ecosystem are influenced by the spatial organization of its cells. We aimed to study the structure, architecture, and cell-cell dynamics of the heterogeneous liver cancer tumor microenvironment using spatially resolved multiplexed imaging.We performed co-detection by indexing multiplexed immunofluorescence imaging on 68 HCC biopsies from Thai patients [(Thailand Initiative in Genomics and Expression Research for Liver Cancer (TIGER-LC)] as a discovery cohort, and then validated the results in an additional 190 HCC biopsies from Chinese patients [Liver Cancer Institute (LCI)]. We segmented and annotated 117,270 and 465,632 cells from the TIGER-LC and LCI cohorts, respectively. We observed 4 patient groups of TIGER-LC (IC1, IC2, IC3, and IC4) with distinct tumor-immune cellular interaction patterns. In addition, patients from IC2 and IC4 had much better overall survival than those from IC1 and IC3. Noticeably, tumor and CD8 + T-cell interactions were strongly enriched in IC2, the group with the best patient outcomes. The close proximity between the tumor and CD8 + T cells was a strong predictor of patient outcome in both the TIGER-LC and the LCI cohorts. Bulk transcriptomic data from 51 of the 68 HCC cases were used to determine tumor-specific gene expression features of our classified subtypes. Moreover, we observed that the presence of immune spatial neighborhoods in HCC as a measure of overall immune infiltration is linked to better patient prognosis.Highly multiplexed imaging analysis of liver cancer reveals tumor-immune cellular heterogeneity within spatial contexts, such as tumor and CD8 + T-cell interactions, which may predict patient survival.

  View details for DOI 10.1097/HEP.0000000000000600

  View details for PubMedID 37725716

  View details for PubMedCentralID PMC10948323

• A nondepleting anti-CD19 antibody impairs B cell function and inhibits autoimmune diseases JCI INSIGHT Boyles, J. S., Sadowski, D., Potter, S., Vukojicic, A., Parker, J., Chang, W. Y., Ma, Y. L., Chambers, M. G., Nelson, J., Barmettler, B., Smith, E. M., Kersjes, K., Himes, E. R., Lin, C., Lucchesi, J., Brahmbhatt, J., Sina, R., Martin, J. A., Maestri, E., Wiethoff, C. M., Dyas, G. L., Linnik, M. D., Na, S., Witcher, D. R., Budelsky, A., Rubtsova, K. 2023; 8 (13)

  Abstract

  B cells contribute to multiple aspects of autoimmune disorders, and B cell-targeting therapies, including B cell depletion, have been proven to be efficacious in treatment of multiple autoimmune diseases. However, the development of novel therapies targeting B cells with higher efficacy and a nondepleting mechanism of action is highly desirable. Here we describe a nondepleting, high-affinity anti-human CD19 antibody LY3541860 that exhibits potent B cell inhibitory activities. LY3541860 inhibits B cell activation, proliferation, and differentiation of primary human B cells with high potency. LY3541860 also inhibits human B cell activities in vivo in humanized mice. Similarly, our potent anti-mCD19 antibody also demonstrates improved efficacy over CD20 B cell depletion therapy in multiple B cell-dependent autoimmune disease models. Our data indicate that anti-CD19 antibody is a highly potent B cell inhibitor that may have potential to demonstrate improved efficacy over currently available B cell-targeting therapies in treatment of autoimmune conditions without causing B cell depletion.

  View details for DOI 10.1172/jci.insight.166137

  View details for Web of Science ID 001024358200001

  View details for PubMedID 37427592

  View details for PubMedCentralID PMC10371335