page 2985, Panigrahi et al. show that this genetic editing is faulty in patients with two kinds of autoimmune disease. The results could lead to new tests and refined treatments for these diseases.
During development in the bone marrow, maturing B cells reshuffle their antibody genes to fashion defenses against a wide variety of pathogens. But these rearrangements can also yield antibodies that target self antigens and provoke autoimmune diseases. To forestall misdirected attacks, self-targeting B cells often undergo further recombination, known as receptor editing, which reshapes their antibody genes.
But receptor editing seems to falter in B cells from patients with autoimmune diseases, Panigrahi et al. report. The researchers gauged the amount of rearrangement in a DNA segment called RS. Although RS doesn't code for part of the antibody, rearrangements there reflect the cell's attempts to fix potentially dangerous antibody genes by reshuffling nearby coding segments. About 30% of patients with lupus or type I diabetes exhibited abnormally low amounts of RS rearrangement, the researchers found. This reduced level of editing might allow self-reactive B cells to escape correction and lead to autoimmune attacks.
Immune tolerance can break down at several points, and reduced receptor editing points to a flaw that develops before B cells exit the bone marrow. Current autoimmune treatments that temporarily deplete B cells are less likely to work in patients with such early-arising problems, the researchers suggest, because the number of self-attacking B cells might quickly rebound. Thus, measuring levels of RS rearrangement might help doctors tailor treatments for patients and allow earlier identification of people prone to autoimmunity.