Can certain antibody-based treatments be useful in autoimmune diseases and asthma?

     Recently published research from the University of Alabama at Birmingham suggests a role for never-before-considered drug classes in the treatment of autoimmune and allergic diseases.

     The results advance the current understanding of the way the body's initial, vague reaction to any invading organism expands into a precise and massive counterattack. That expansion starts when a dendritic (tree-like) cell swallows a piece of an encountered invader, passes it to the nearest lymph node, and presents it there for notice by lymphocytes, the workhorse cells of the immune system.

     According to the current model, the dendritic cells first must encounter T lymphocytes in the paracortex, or T cell zone, within the node. There the interaction enables the lymphocytes to expand into an army ready to attack the invader. The research team discovered that, although immune response works this way during viral flu infections, not always is it the case in other attacks. For example, when the body is infested with parasitic worms, dendritic cells link with T cells near B lymphocytes, under control of B cell-related signals and outside the T cell zone.

     Frances Lund, Ph.D., corresponding author of the study and chair of the University of Alabama at Birmingham School of Medicine's Department of Microbiology, says, "Considering that diseases from asthma to lupus can occur because the system mistakenly ramps up the same types of T cell responses it normally uses against worms, our finding that B lymphocytes control the T cell/dendritic cell interactions that trigger such responses has important, practical implications."

     The authors believe that some interactions trap T cells near the B cell area, and that proximity determines the kind of cells they become next. Those receiving the strongest signals become the T helper follicular cells with which B cells must partner to produce antibodies specific to the current organism capable of producing a disease. Those receiving weaker signals become the Th2 effectors that travel to the infection site to cause the histamine release and intestinal muscle contractions that help to expel worms. This is good. But on the negative side, sometimes T helper follicular cells help B cells produce high affinity autoantibodies that recognize the body's own cells as foreign and can destroy the kidneys of lupus patients and the joints of rheumatoid arthritis patients. Also, the cells may confuse allergens in the lung, like house dust mites, with worms. This mistake causes histamine release and bronchoconstriction in the lungs, major clinical symptoms of asthma.

     Dr. Lund says, "The field now has cause to look at several experimental and existing drugs known to interrupt B cell signals as potential treatments for diseases driven by T cells." He asks, "Could such antibody-based treatments be useful against some autoimmune diseases and asthma?" He suggests that "time and further studies will tell."

--Source: Adapted from "Discovery Expected to Shift Research Direction in Lupus and Asthma, " Science Daily, May 27, 2012, via Newswise