(NEW YORK -October 3, 2018) - In a study published today in Science Translational Medicine, Mount Sinai researchers describe for the first time a mechanism that may shrink collections of immune cells in the gastrointestinal (GI) tract, called lymphoid aggregates, where HIV may lay sequestered. These findings may be of interest to scientists who are involved in researching the cure for HIV infection in light of the strong role that the intestines play in it.
The study builds on research by the same team which found in 2004 that the intestines are specifically targeted by HIV at the earliest stage of infection. "We know from our earlier research that intestinal immune cells called CD4+ T cells are profoundly depleted during the earliest stages of HIV infection. Newer research from other groups has found that CD4 + T cells that migrate to the gut, and bear a receptor called a4b7, are highly susceptible to HIV," says Saurabh Mehandru, MD, Associate Professor of Medicine (Gastroenterology) at the Icahn School of Medicine at Mount Sinai and the senior author on this study. Dr. Mehandru directs an immunology lab, part of the Division of Gastroenterology at the Icahn School of Medicine. The Mehandru Lab studies mucosal immunology as it pertains to immune deficiency states such as HIV infection and inflammatory disorders, with inflammatory bowel disease (IBD) being a focal point.
"Now, 14 years later, we have discovered how anti-a4b7 therapy can significantly, and rather unexpectedly, lead to the attenuation of lymphoid aggregates," continues Dr. Mehandru. This is the first report of reduction in GI-associated lymphoid aggregates by a therapeutic intervention in patients with HIV-1 infection. "As such, these data describe a new mechanism of action of treatments targeting the a4b7 receptor and define a rational basis for the use of these treatments in HIV-1 infection and beyond," says Dr. Mehandru.
Study authors, led by PhD student Mathieu Uzzan, designed a study that involved a cohort of six individuals with mild IBD and concomitant HIV-1 infection receiving anti-a4b7 treatment, specifically vedolizumab (VDZ). VDZ has become a frontline strategy in the management of patients with IBD, in whom it has demonstrated strong efficacy and an excellent safety profile. The investigators studied immune cells in the blood and the intestines and describe the immunological and virological effects of VDZ therapy over a 30-week period.
"The therapy was tolerated well, with only minor adverse events reported. We were surprised by the impact of treatment on lymphoid aggregates in the GI tract of patients with HIV-1 infection. We believe these initial findings could have significant implications for HIV-1 infection, perhaps in combination with other agents such as broadly neutralizing anti-HIV antibodies," says Dr. Mehandru.
Research was facilitated by scientists at the University of Hawaii, the Wistar Institute, the University of Montreal, and the University of Minnesota.
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The Mount Sinai Health System is New York City's largest integrated delivery system encompassing seven hospital campuses, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai's vision is to produce the safest care, the highest quality, the highest satisfaction, the best access and the best value of any health system in the nation. The System includes approximately 6,600 primary and specialty care physicians; 11 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. The Icahn School of Medicine is one of three medical schools that have earned distinction by multiple indicators: ranked in the top 20 by U.S. News & World Report's "Best Medical Schools", aligned with a U.S. News & World Report's "Honor Roll" Hospital, it is ranked as a leading medical school for National Institutes of Health funding, and among the top 10 most innovative research institutions as ranked by the journal Nature in its Nature Innovation Index. This reflects a special level of excellence in education, clinical practice, and research. The Mount Sinai Hospital is ranked No. 18 on U.S. News & World Report's "Honor Roll" of top U.S. hospitals; it is one of the nation's top 20 hospitals in Cardiology/Heart Surgery, Gastroenterology/GI Surgery, Geriatrics, Nephrology, and Neurology/Neurosurgery, and in the top 50 in six other specialties in the 2018-2019 "Best Hospitals" issue. Mount Sinai's Kravis Children's Hospital also is ranked nationally in five out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology and 44th for Ear, Nose, and Throat, while Mount Sinai Beth Israel, Mount Sinai St. Luke's and Mount Sinai West are ranked regionally. For more information, visit http://www.mountsinai.org/, or find Mount Sinai on Facebook, Twitter and YouTube.
Journal
Science Translational Medicine