The role of autoantibodies in the syndromes of orthostatic intolerance: a systematic review

Figures & data

Table 1. Alpha and beta adrenergic receptors and their main physiological effects.

Receptor	Location	Physiological activity upon stimulation
α1A	Blood vessels mainly skin and GI tract	Smooth muscle contraction leading to vasoconstriction
α2A	Brain, presynaptic sympathetic nerves	Decrease blood pressure and lower plasma norepinephrine
α2B	Kidney	Water retention and vasoconstriction
α2C	Skin vasculature	Cold induced vasoconstriction
β1AR	Heart	Increase heart rate and stroke volume
	Juxtaglomerular cells of the kidney	Increase renin release causing fluid retention and water restriction
β2AR	Heart	Increase heart rate and stroke volume
	Blood vessels mainly skeletal muscles	Smooth muscle relaxation leading to vasodilation

Table 2. Adrenergic antibodies in patients with orthostatic hypotension and POTS.

Author	Year	Group of patients tested	Receptor associated Autoantibodies	No. of patients with positive antibody/No. Of total patients, No. of controls with positive antibodies/No. of total control
Yu et al [15]	2012	Idiopathic OH	(β1/2AR)	5/6, 0/10
Li et al [24]	2012	10 idiopathic OH and 10diabetics with OH	β2AR	7/20, 0/10
Li et al [3]	2014	POTS	β1AR	14/14, 0/10
		POTS	β2AR	7/14, 0/10
		POTS	α1AR	14/14, 0/10
Fedorowski [25]	2016	POTS	α1AR	8/17, 0/11
		POTS	β1AR	11/17, 0/11
		POTS	β2AR	12/17, 0/11

Table 3. Cholinergic antibodies in patients with dysautonomia.

Author	Year	Receptor	Patient’s population	No. of patients with positive antibody/No. Of total patients, No. of controls with positive antibodies/No. of total control	Comments
Vernino [11]	2000	α3-AChR Ab	POTS	6/67, N/A
Sandroni [28]	2004	ganglionic AChR	Orthostatic intolerance, autonomic neuropathy	Compared 19 seropositive with 87 seronegative patients	Seropositive patients are more likely to have orthostatic hypotension with other cholinergic symptoms like sicca complex or GI symptoms.
Gibbons [42]	2008	AChR	Autoimmune autonomic ganglionopathy	3/3, N/A	Three patients with dysautonomia and nicotine receptor antibody refractory to medical treatment who responded to immunomodulatory therapy
Mckeon [13]	2009	α3-AChR Ab	Paraneoplastic neurological autoimmunity	155/15,000 (1%) with positive titers were examined. 13 had pandysautonomia, 5 had orthostatic hypotension only.	High antibody values ≥1.00 nmol/L, were associated with pandysautonomia
Gibbons [29]	2009	AChR	Autoimmune autonomic ganglionopathy	8/8, N/A	Higher antibody titers were associated with more severe orthostatic hypotension
Yu [15]	2012	M2/M3 receptor Ab	Idiopathic OH	6/6, 0/10	Serum from patients caused dose-dependent vasodilation in rat cremaster arteriole.
Li [24]	2012	M3R	10 idiopathic OH and 10 diabetics with OH	13/20, 0/10	Serum from patients caused vasodilation in rat cremaster arteriole. Their effect was dose-dependent and inhibited by adding atropine

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