Title : Potentially curative treatment of pemphigus and pemphigoid
Abstract:
A cure from pemphigus and pemphigoid, like any other autoan1body-mediated autoimmune disease, should commence when the cri1cal mass of autoreac1ve plasma cells dies off. Since the life span of autoan1body-secre1ng plasma cells is shorter than that of the classically long-lived plasma cells producing protec1ve (normal) IgG an1bodies, the pa1ent should be kept in clinical remission for at least 2 years, in expecta1on that the cri1cal mass of autoreac1ve plasma cells dies off during this 1me-frame. Pemphigus and pemphigoid usually flare during the first 2 years, especially when treatment is discon1nued aZer 1 year. Each relapse may aggravate autoimmunity to already targeted self-an1gens, and also induce new autoan1bodies, due to self-immuniza1on with sequestered an1gens released from damaged kera1nocytes and/or intramolecular epitope spreading. A complete and stable clinical remission of pemphigus and pemphigoid can be achieved using the mul1drug treatment approach that: i) protects kera1nocytes from autoan1body aIack and allows rapid healing of erosions by a brief course of systemic cor1costeroids and mitochondrion-protec1ng drugs; ii) selec1vely eliminates pathogenic autoan1bodies by intravenous immunoglobulin (IVIg); and iii) inhibits autoan1body produc1on by cytotoxic immunosuppressors (PMID: 30047585). This regimen offers a lower relapse rate compared to the FDA-approved prednisone/rituximab regime. Rituximab does not target the autoan1body-secre1ng plasma cells. Instead, it targets the CD20 posi1ve precursor B cells regardless of their relevance to the disease, whereas the majority of B cell popula1ons repopulate aZer treatment. In contrast, IVIg selec1vely and predictably eliminates pathogenic an1bodies. While both normal and pathogenic an1bodies are cleared at the same rate, normal an1bodies are replenished by donors’ IgGs. Therefore, not surprisingly, treatment with the mul1-drug protocol incorpora1ng IVIg leads to a stable remission off drugs for longer than 5 years in 88% of pa1ents, whereas 32% of pemphigus pa1ents who were in clinical remission off prednisone/rituximab therapy relapse within 5 years aZer treatment. Overall, treatment of pemphigus and pemphigoid pa1ents with the mul1-drug protocol provides for the following clinical outcomes: i) abrupt cessa1on of development of new and rapid healing of exis1ng lesions; ii) prompt disappearance of the func1onal impairment associated with the disease; iii) complete clinical remission; iv) preven1on of flares; and v) lack of serious side effects.
