Based on one of the largest primary immunodeficiency clinics in the Northeast (and possibly in the US) established by Charlotte Cunningham-Rundles, this program focuses on the mechanisms and treatment of primary human immune defects. The clinic referral population spans all age groups from infants to the elderly. A central research focus for some years has been on the pathogenesis and treatment of B cell defects, however due to the complex nature of B cell activation; the genetic causes of B cell failure are multiple and include defined molecular defects in the bone marrow, lymph node and cellular compartments. Using whole genomic sequencing we have now elucidated new causes of B cell failure, leading to unique clinical manifestations. Based on experience as an established program, Mount Sinai is also New York State referral center for infants identified by newborn screening, with suspected severe T cell defects. This program also reinforces the work of the Pediatric Hematology Division as infants with severe defects require stem cell transplantation.  

Another unique Immune deficiency program at the Icahn School of Medicine at Mount Sinai was established by Paula Busse for patients with genetic and acquired forms of C1 inhibitor deficiency. Also of the largest in the nation, this program had led to a number of clinical trials with novel agents designed to prevent the medical complications of this severe immune defect. Furthermore, several investigators joined the program recently, adding expertise in various areas of immune deficiency research. Dusan Bugonovic studies type I interferonopathies, Minji Byun investigates genetic causes of rare inflammatory disorders, Yuval Itan conducts research on large-scale computational discovery of genes and pathways causing immune deficiencies and PJ Maglione uses translational research in primary immunodeficiency to identify new therapeutic targets for immunological disease.

The Primary Immunodeficiency program has been supported by a long-running program grant and several R01s, a NIH supported national cooperative grant, industry funds, clinical trials, and substantial funding from the Jeffrey Model Foundation. More recently, additional outreach work will be funded by a new Clinical Sequencing Exploratory Research (CSER). The work with New York State (NYS) has led to a new NYS grant to Mount Sinai, from the Department of Health, and funded by the Center for Disease Control. 

A confounding feature of human immune deficiency is immune dysregulation. For this reason, patients with primary immune defects are likely to develop inflammatory and autoimmune diseases. One consequence of this has been the increasing use of targeted biologics in subjects with known gene defects. With the growth of selected and targeted therapies for immune based diseases as a whole, some years ago the Clinical Immunology team established a biologics infusion program. This has now grown to a new Non-Cancer Infusion Center, incorporating biologic treatments for an increasing number of immune based diseases referred from a number of other services within the Mount Sinai Health System.

The Clinical Immunology Division along with the Pediatric Division of Allergy and Clinical Immunology serves as a stellar teaching site for the Allergy and Clinical Immunology Fellowship program at the Icahn School of Medicine at Mount Sinai, Downstate Medical Center, and Winthrop University Hospital. With increasing focus on genetic diagnosis, the Immunodeficiency Program increasingly relies upon genetic testing for diagnosis and for design of best therapeutic strategies.

Investigators with a major focus in immunodeficiency include: Charlotte Cunningham-Rundles, Yizhou Dong, Rebecca Powell,