Effect of therapeutic plasma exchange on immunoglobulins in myasthenia gravis.
An integrated understanding of therapeutic plasma exchange (TPE) effects on immunoglobulins, autoantibodies, and natural or acquired (vaccine) protective antibodies in patients with autoimmune myasthenia gravis (MG) is lacking. Prior studies measured TPE effects in healthy volunteers or heterogeneous autoimmune disease populations. We prospectively profiled plasma IgA, IgM, IgG, IgG subclasses (IgG1-4), acetylcholine receptor autoantibodies (AChR+), and protective antibodies in patients with AChR + MG receiving TPE for an exacerbation. TPE was performed according to institutional practice and patients were profiled for up to 12 weeks. Ten patients were enrolled (median age = 72.9 years; baseline MG-Composite = 21; median TPE treatments = 6 during their first course) and all improved. The maximum decrease in all immunoglobulins, including AChR autoantibodies, was achieved on the final day of the first TPE course (∼60-70% reduction). Three weeks post-TPE, mean AChR autoantibody, total IgG, IgG1, and IgG2 titers were below the reference range and had not recovered within 20% of baseline, whereas other measured immunoglobulins approached baseline values. We did not generally observe an "overshoot" of immunoglobulins above pre-TPE levels or accelerated recovery of pathologic AChR autoantibodies. Protective antibody profiles showed similar patterns as other IgGs and were detectable at levels associated with protection from infection. A slow return to baseline for IgGs (except IgG3) was observed, and we did not observe any obvious effect of concomitant medications on this recovery. Collectively, these findings enhance our understanding of the immunological effects of TPE and further support the concept of rapid immunoglobulin depletion for the treatment of patients with MG.
a Division of Neuromuscular Disease, Department of Neurology , Duke University Medical Center , Durham , NC , USA.
Jeffrey T
JT
Guptill
a Division of Neuromuscular Disease, Department of Neurology , Duke University Medical Center , Durham , NC , USA.
Vern C
VC
Juel
a Division of Neuromuscular Disease, Department of Neurology , Duke University Medical Center , Durham , NC , USA.
Janice M
JM
Massey
a Division of Neuromuscular Disease, Department of Neurology , Duke University Medical Center , Durham , NC , USA.
Amanda C
AC
Anderson
b Neuromuscular Disorders Section, Department of Neurology , The University of North Carolina , Chapel Hill , NC , USA.
Manisha
M
Chopra
c Division of Surgical Sciences, Department of Surgery , Duke University Medical Center , Durham , NC , USA.
John S
JS
Yi
d Takeda TDC Europe , London , UK.
Ehsanollah
E
Esfandiari
e UCB Biosciences , Slough , UK , and.
Tim
T
Buchanan
e UCB Biosciences , Slough , UK , and.
Bryan
B
Smith
e UCB Biosciences , Slough , UK , and.
Paul
P
Atherfold
f Veramed Limited , West London , UK.
Emma
E
Jones
b Neuromuscular Disorders Section, Department of Neurology , The University of North Carolina , Chapel Hill , NC , USA.
James F
JF
Howard
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015415:Biomarkers; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007136:Immunoglobulins / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000097:blood* / Q000276:immunology / Q000628:therapy*; D010951:Plasma Exchange / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007136:Immunoglobulins
IgG; Myasthenia gravis; immunoglobulins; plasma exchange; plasmapheresis
Neurology. 2011 Jun 7;76(23):2017-23
21562253
J Lab Clin Med. 1984 Jul;104(1):35-43
6736750
Arch Neurol. 1981 Aug;38(8):478-81
7247783
Transfusion. 1982 Jan-Feb;22(1):54-8
7064208
Ann N Y Acad Sci. 2003 Sep;998:440-4
14592912
Continuum (Minneap Minn). 2014 Oct;20(5 Peripheral Nervous System Disorders):1413-25
25299290
Eur J Immunol. 2007 Mar;37(3):849-63
17323412
Curr Treat Options Neurol. 2005 Jan;7(1):3-14
15610702
Autoimmunity. 2010 Aug;43(5-6):436-45
20187712
Clin Exp Immunol. 1987 Jan;67(1):82-8
3621677
J Clin Apher. 1995;10(4):210-7
8770715
Blood Transfus. 2007 Jul;5(3):164-74
19204770
J Clin Invest. 2006 Nov;116(11):2843-54
17080188
Am J Kidney Dis. 2008 Dec;52(6):1180-96
18562061
MMWR Recomm Rep. 2011 Nov 25;60(RR-7):1-45
22108587
Neurology. 2010 May 4;74(18):1434-40
20439845
Annu Rev Microbiol. 1965;19:301-38
4157636
Neurology. 2000 Jul 12;55(1):16-23
10891897