Beyond the skin: B cells in pemphigus vulgaris, tolerance and treatment.

ABSTRACT

Pemphigus vulgaris (PV) is a rare autoimmune bullous disease characterized by blistering of the skin and mucosa owing to the presence of autoantibodies against the desmosome proteins desmoglein 3 and occasionally in conjunction with desmoglein 1. Fundamental research into the pathogenesis of PV has revolutionized its treatment and outcome with rituximab, a B-cell-depleting therapy. The critical contribution of B cells to the pathogenesis of pemphigus is well accepted. However, the exact pathomechanism, mechanisms of onset, disease course and relapse remain unclear. In this narrative review, we provide an overview of the fundamental research progress that has unfolded over the past few centuries to give rise to current and emerging therapies. Furthermore, we summarize the multifaceted roles of B cells in PV, including their development, maturation and antibody activity. Finally, we explored how these various aspects of B-cell function contribute to disease pathogenesis and pave the way for innovative therapeutic interventions.

Pemphigus vulgaris (PV) is a rare autoimmune disease, in which the immune system attacks itself and causes blisters on the skin and inside the mouth. This happens because the body mistakenly attacks specific proteins (called desmosomes) that keep the skin together. Globally, this disease affects anywhere from 0.5 to 16.1 people per million, often older than 50 years. PV is life-threatening when left untreated. From carrying out research as far back as the 1700s, we have made significant strides in understanding PV. For example, research has led to a new treatment with the antibody rituximab, which works by eliminating the cells of the immune system that attack desmosomes (called B cells). However, after therapy is completed, the disease often returns because the same troublesome B cells reappear. There are multiple places that are involved when the body attacks desmosomes. The problems range from the bone marrow where the B cells are made and selected to the ways these cells change as they move around the body. It takes a rare combination of these changes to switch from a normal immune system to one that causes PV. Clinicians and researchers are currently developing new treatment options to better target this skin disease. We want to emphasize that research should continue to uncover how the disease works because a better understanding promotes the development of new therapies, and perhaps even a cure. This is vital, because PV can significantly lower the quality of life of people living with this skin disease.