Table 2.

Summary of some known clinical and immunological features of MG

	AChR MG	MuSK MG	LRP4 MG
Clinical features	Incidence has 2 peaks: 3rd decade in women; 7th decade in men Prominent ocular muscle involvement Improved by ACheI Improved by IVIg, TPE Most patients respond to immunosuppression [40, 41] Somewhat variable response to RTX [42]	85% female Symptom onset peaks in 4th decade Bulbar and proximal weakness common Prominent muscle atrophy Crisis frequent early in clinical course Poor response to ACheI Excellent TPE response Often requires more aggressive immunosuppresion Frequently dramatic response to RTX [2, 3]	Female predominance Peak incidence in 4th–5th decade Most improved by ACheI Response to immunosuppression similar to AChR MG [43, 44]
HLA association	HLA-DR3, B8, DR9 (Asian): early onset [45–48] HLA-DR2, B7: late onset [49]	HLA-DR14, DQ5 [50, 51]	Unknown
Autoantibodies	IgG1, IgG3	Primarily IgG4 [29]	IgG1 [44]
T cells	CD4 T cells likely play a prominent role in disease proprogation [37, 52–54] Th1 proinflammatory pathway predominates [55, 56] CD8 T cells less important to disease pathophysiology [36, 57, 58]	Polyfunctional T cell responses Possible Th1, Th17 proinflammatory pathway	Unknown
B cells	Increased immunoglobulin secreting thymic B cells [59] Peripheral B cells are primed for AChR autoantibody production [60] Normal overall B cell numbers; fewer naïve B cells; increased memory B cells after immunosuppression; increased plasmablasts [61] Increased AChR-specific B cells [62]	Unknown	Unknown
Tregs	Normal or decreased peripheral Treg numbers [63–68] Reduced FOXP3 mRNA expression in PBMCs [69] Impaired Treg function [65, 70] Normal thymic Treg numbers [63] Impaired thymic CD4+CD25+ function , normal numbers [71] Reduced Tregs in thymoma [72, 73]	Normal Treg numbers Normal CD39 expression	Unknown
Bregs	Unknown	Unknown	Unknown
Cytokines	Increased Th1 associated cytokines IFN-γ, IL-10, and IL-2/sIL-2R [74–79] Increased peripheral Th2 associated cytokines IL-4, IL-6 [74, 80, 81] Increased peripheral TGF-β; TGF-β higher following thymectomy [74, 82] Elevated peripheral IL-17 [39] Elevated peripheral BAFF [83, 84]	Unknown	Unknown
Complement	C3 and C9 deposition on postsynaptic membrane [57, 85] Increased CD21 complement receptor on B cells [86]	Rare complement deposition on the postsynaptic membrane [32, 87]	Unknown, but IgG1 autoantibodies have potential to cause complement-mediated damage
Thymic changes	Frequent germinal centers, anti-AChR lymphocytes, and myoid cells expressing AChR [88–91] Thymoma in 10–15% of patients [92] Increased production of IL-6, IL-2, IL-1, IL-1β in hyperplastic thymus [93–96] Low AIRE expression in thymomas [72]	Rare lymphofollicular hyperplasia, germinal centers [4, 5] Very rare microscopic thymoma [2, 3]	Unknown

Abbreviations: AChR=acetylcholine receptor; ACheI= acetylcholine esterase inhibitor; AIRE=autoimmune regulator gene; BAFF=B-cell activating facor; HLA=human leukocyte antigen; IVIg=intravenous immunoglobulins; LRP= lipoprotein-related protein 4; MG=myasthenia gravis; MuSK=muscle specific kinase; RTX=rituximab; sIL-2R=soluble IL-2 receptor; TPE=therapeutic plasma exchange