Abstract
BackgroundHigh doses of pooled polyclonal IgG are commonly used to treat numerous autoimmune diseases. Their mode of action nevertheless remains only partially explained. At the same time, until now, no early biological marker has been able to predict their efficacy.Methodology/Principal FindingsIn a first pilot retrospective analysis, we reviewed white blood cell counts and blood smears in consecutive patients with autoimmune disease (n = 202) and non-autoimmune disease (n = 104). Autoimmune patients received either intravenous immunoglobulin (IVIg, n = 103), plasma exchange (n = 78) or no specific treatment (n = 21). We then prospectively monitored consecutive autoimmune patients with IVIg injection (n = 67), or without any specific treatment (n = 10) using the same routine laboratory tests, as well as flow cytometry. Both retrospective and prospective analyses identified large plasma-cell mobilization exclusively in IVIg-treated autoimmune patients 7 days after initiation of treatment. The majority of IVIg-mobilized plasma cells were immature HLA-DRhigh/CD138low/CXCR4low plasma cells expressing intracellular immunoglobulin G which were neither IVIg- nor human IgG-specific. Importantly, we found a strong negative correlation between the absolute number of IVIg-mobilized plasma cells and time to improve neurological function in both retrospective and prospective studies of Guillain-Barré syndrome (GBS), (r = −0.52, p = 0.0031, n = 30, r = −0.47, p = 0.0028, n = 40, respectively).Conclusions/SignificanceIVIg promotes immature plasma-cell mobilization in patients with GBS, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis and inflammatory myopathy. Prominent day 7 plasma-cell mobilization is a favourable prognostic marker in patients with GBS receiving IVIg treatment.
Highlights
Polyclonal IgG pooled from the serum of thousands of donors is widely used to confer passive protection to immune deficient patients and as an anti-inflammatory agent [1]
We show that a prominent plasmacytosis was very frequently associated with administration of Intravenous immunoglobulin (IVIg) in autoimmune patients
These findings indicate that plasma cell count on the 7th day of IVIg will be useful to distinguish patients that have beneficial IVIg effects from those who would need more individualized treatment, and to reconsider the treatment regimen during the acute phase of GBS in the latter
Summary
Polyclonal IgG pooled from the serum of thousands of donors is widely used to confer passive protection to immune deficient patients and as an anti-inflammatory agent [1]. Intravenous immunoglobulin (IVIg) therapy is approved by Food and Drug Administration for the treatment of immune thrombocytopenic purpura, Kawasaki disease, primary immunodeficiency, bone marrow transplantation, chronic B-cell lymphocytic leukemia, and pediatric HIV infection [2]. There has existed no biological marker which may be used to evaluate the efficacy of this treatment. The lack of a biological marker is troublesome when trying to evaluate the efficacy of IVIg during the course of chronic autoimmune diseases such as CIDP, MG and IM. GBS is an autoimmune polyneuropathy, characterized by precedent infection and acutely progressive motor weakness. High doses of pooled polyclonal IgG are commonly used to treat numerous autoimmune diseases. Their mode of action remains only partially explained. Until now, no early biological marker has been able to predict their efficacy
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