Abstract
In this concept paper, the authors present a unique and novel protocol to treat autoimmune diseases that may have the potential to reverse autoimmunity. It uses a combination of B cell depletion therapy (BDT), specifically rituximab (RTX) and intravenous immunoglobulin (IVIg), based on a specifically designed protocol (Ahmed Protocol). Twelve infusions of RTX are given in 6–14 months. Once the CD20+ B cells are depleted from the peripheral blood, IVIg is given monthly until B cells repopulation occurs. Six additional cycles are given to end the protocol. During the stages of B cell depletion, repopulation and after clinical recovery, IVIg is continued. Along with clinical recovery, significant reduction and eventual disappearance of pathogenic autoantibody occurs. Administration of IVIg in the post-clinical period is a crucial part of this protocol. This combination reduces and may eventually significantly eliminates inflammation in the microenvironment and facilitates restoring immune balance. Consequently, the process of autoimmunity and the phenomenon that lead to autoimmune disease are arrested, and a sustained and prolonged disease and drug-free remission is achieved. Data from seven published studies, in which this combination protocol was used, are presented. It is known that BDT does not affect check points. IVIg has functions that mimic checkpoints. Hence, when inflammation is reduced and the microenvironment is favorable, IVIg may restore tolerance. The authors provide relevant information, molecular mechanism of action of BDT, IVIg, autoimmunity, and autoimmune diseases. The focus of the manuscript is providing an explanation, using the current literature, to demonstrate possible pathways, used by the combination of BDT and IVIg in providing sustained, long-term, drug-free remissions of autoimmune diseases, and thus reversing autoimmunity, albeit for the duration of the observation.
Highlights
The treatment of autoimmune disease is a challenge and priority as they affect 50 million individuals in the United States, and currently they collectively are the third most common disease category [1, 2]
This study demonstrated that it was multiple infusions, at defined intervals, after clinical recovery that produced a sustained prolonged clinical remission [28]
Into October 2006, we reported successful clinical outcomes in 11 patients with severe widespread pemphigus vulgaris (PV) involving the skin and multiple mucosae [41]
Summary
The treatment of autoimmune disease is a challenge and priority as they affect 50 million individuals in the United States, and currently they collectively are the third most common disease category [1, 2]. Twelve patients with recalcitrant bullous pemphigoid (BP) who had failed CS and ISA, had multiple relapses on them, some had already received RTX by RA protocol, were treated by the combination of RTX and IVIg and followed for a mean of 73.8 months (6 years) post therapy were reported in 2015 [29]. Followed for 1-year post therapy [44] and for additional 8 years, these six patients with recalcitrant OCP, had complete clinical and serological remission, with normal levels of B cells, and a good quality of life and most importantly preventions of blindness. A British group in 2016 reported three patients with MMP and one with linear IgA bullous disease, non-responsive to conventional therapy, all four blind in one eye, treated with two cycles of RTX and 2–9 monthly infusions of IVIg [46].
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