SUMMARY
Keith Sacco, M.D., is an allergist-immunologist. Dr. Sacco studies immune imbalances across inflammatory syndromes, inborn errors of immunity, and postinfectious or posttreatment immune complications. He defines mechanistic immune endotypes that explain why certain patients develop persistent inflammation, vascular permeability or atypical immune responses despite otherwise unremarkable standard testing.
Dr. Sacco also studies conditions including idiopathic angioedema, clonal mast cell disorders, autoinflammatory diseases, and immune dysfunction following infections or cancer therapy.
Dr. Sacco integrates clinical immunology, high-dimensional immune profiling and genomic analysis to link immune phenotypes with underlying molecular mechanisms. His work from fellowship and subsequent studies has characterized cytokine networks, T-cell activation states and interferon signaling patterns across hyperinflammatory syndromes and primary immunodeficiencies. These approaches enable improved condition classification and risk stratification.
A central theme of Dr. Sacco's work is time-dependent and environmentally influenced immunity, including circadian biology, immunometabolism and environmental exposures. His approach combines clinical cohorts with systems-level data to identify applicable biomarkers and therapeutic targets that can guide precision diagnosis and treatment across heterogeneous immune-mediated diseases.
Focus areas
- Angioedema and vascular inflammation. Dr. Sacco investigates idiopathic and inflammatory angioedema as a heterogeneous syndrome driven by distinct biological pathways. He uses clinical phenotyping and genomic integration to define mechanistic endotypes, including overlap with autoimmune diseases such as Sjogren syndrome and systemic lupus erythematosus. The goal of Dr. Sacco's research is to enable targeted, mechanism-based therapies.
- Clonal mast cell disorders. Dr. Sacco studies systemic mastocytosis and related mast cell-driven diseases. He improves diagnostic accuracy and identifies biomarkers of mast cell activation. His work addresses gaps in distinguishing clonal from nonclonal disease and in predicting disease behavior and treatment response.
- Innate immune imbalance syndromes. Dr. Sacco examines autoinflammatory conditions and inborn errors of immunity characterized by changes in innate immune signaling. He combines functional immunophenotyping with genomic approaches to define pathways driving chronic inflammation and to refine genotype-phenotype correlations.
- Postinfectious and posttreatment immunity. Dr. Sacco explores immune imbalance following infections such as SARS-CoV-2 and after cancer therapies. His research includes characterization of interferon responses, immune cell activation states and long-term immune recovery patterns that influence susceptibility to complications.
- Environmental and temporal immunology. Dr. Sacco studies how circadian rhythms, metabolism, microbiome changes and environmental exposures — such as occupational agents and microplastics — influence immune cell behavior. Through his research, Dr. Sacco establishes clinically applicable frameworks for time-dependent immune regulation.
Significance to patient care
Many patients with swelling, ongoing inflammation or unusual immune system symptoms can go years without clear answers. Dr. Sacco's research helps find the root causes of these conditions by linking symptoms to the way the immune system works. By improving how these conditions are grouped, patients can get more-accurate diagnoses and treatments that fit their needs. His work also helps medical teams manage complications after infections or cancer treatment. Dr. Sacco's research aims to reduce diagnosis delays, improve treatment choices and help patients have better long-term health.
Professional highlights
- Reviewer, Journal of Allergy and Clinical Immunology: In Practice, 2022-present.
- Top 10% of reviewers, Journal of Allergy and Clinical Immunology: In Practice, 2025.
- American Academy of Allergy, Asthma and Immunology:
- Lead, Management of Neutrophil Disorders, Practice Parameter on Management of Inborn Errors of Immunity, 2022-2025.
- Faculty Development Award, 2021.
- Chrysalis Project Award, 2017.
- Reviewer, Frontiers in Allergy, 2022-2024.
- Research Award, Internal Medicine Residency Program, Mayo Clinic, 2018.