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Clinical features of autoimmune autonomic ganglionopathy and the detection of subunit-specific autoantibodies to the ganglionic acetylcholine receptor in Japanese patients.

Nakane S, Higuchi O, Koga M, Kanda T, Murata K, Suzuki T, Kurono H, Kunimoto M, Kaida K, Mukaino A, Sakai W, Maeda Y, Matsuo H - PLoS ONE (2015)

Bottom Line: Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR.The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group.In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan; Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan.

ABSTRACT
Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG.

No MeSH data available.


Related in: MedlinePlus

LIPS for gAChR in the sera from patients with autoimmune autonomic ganglionopathy (AAG) and controls.We tested the sera from patients with AAG, disease controls (DC), and healthy controls (HC). a) Anti-gAChRα3 antibodies were detected in 23 samples. The mean anti-gAChRα3 antibody level in the HC was 0.305 antibody index (A.I.), which was significantly lower than in the AAG samples with a mean level of 1.210 A.I. (p < 0.001). b) Anti-gAChRβ4 antibodies were also detected in seven samples, as shown in Fig. 4B (p = 0.005). The mean anti-gAChRβ4 antibody level in the HC was 0.367 A.I., which was significantly lower than the measn level of 0.618 A.I. in the AAG samples (p < 0.001).
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pone.0118312.g004: LIPS for gAChR in the sera from patients with autoimmune autonomic ganglionopathy (AAG) and controls.We tested the sera from patients with AAG, disease controls (DC), and healthy controls (HC). a) Anti-gAChRα3 antibodies were detected in 23 samples. The mean anti-gAChRα3 antibody level in the HC was 0.305 antibody index (A.I.), which was significantly lower than in the AAG samples with a mean level of 1.210 A.I. (p < 0.001). b) Anti-gAChRβ4 antibodies were also detected in seven samples, as shown in Fig. 4B (p = 0.005). The mean anti-gAChRβ4 antibody level in the HC was 0.367 A.I., which was significantly lower than the measn level of 0.618 A.I. in the AAG samples (p < 0.001).

Mentions: Both the anti-gAChRα3 and anti-gAChRβ4 antibodies were determined by the LIPS assay to be present in 0.0% (0 of 73) of the HC. In contrast, 48% (24 of 50) of the sera from patients with AAG were positive for autoantibodies (p < 0.001, Fig. 4A). The anti-gAChRα3 antibodies were detected in 23 samples and the anti-gAChRβ4 antibodies were detected in seven samples (14.0%), as shown in Fig. 4B (p < 0.001). Both of the antibodies were detected in six samples. The mean anti-gAChRα3 antibody levels in the HC and the DC were 0.305 A.I. and 0.336 A.I., respectively. These levels were significantly lower than the mean level in the AAG samples with a mean level of 1.210 A.I. (p < 0.001, Fig. 4A). Similarly, the mean anti-gAChRβ4 antibody level in HC was 0.367 A.I. and DC was 0.302 A.I., respectively. Those were significantly lower than the AAG samples with a mean level of 0.618 A.I. (p < 0.001, Fig. 4B). In the DC group, we detected anti-gAChRα3 antibodies in the serum of the patient with the suspected case of amyloid neuropathy.


Clinical features of autoimmune autonomic ganglionopathy and the detection of subunit-specific autoantibodies to the ganglionic acetylcholine receptor in Japanese patients.

Nakane S, Higuchi O, Koga M, Kanda T, Murata K, Suzuki T, Kurono H, Kunimoto M, Kaida K, Mukaino A, Sakai W, Maeda Y, Matsuo H - PLoS ONE (2015)

LIPS for gAChR in the sera from patients with autoimmune autonomic ganglionopathy (AAG) and controls.We tested the sera from patients with AAG, disease controls (DC), and healthy controls (HC). a) Anti-gAChRα3 antibodies were detected in 23 samples. The mean anti-gAChRα3 antibody level in the HC was 0.305 antibody index (A.I.), which was significantly lower than in the AAG samples with a mean level of 1.210 A.I. (p < 0.001). b) Anti-gAChRβ4 antibodies were also detected in seven samples, as shown in Fig. 4B (p = 0.005). The mean anti-gAChRβ4 antibody level in the HC was 0.367 A.I., which was significantly lower than the measn level of 0.618 A.I. in the AAG samples (p < 0.001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4366081&req=5

pone.0118312.g004: LIPS for gAChR in the sera from patients with autoimmune autonomic ganglionopathy (AAG) and controls.We tested the sera from patients with AAG, disease controls (DC), and healthy controls (HC). a) Anti-gAChRα3 antibodies were detected in 23 samples. The mean anti-gAChRα3 antibody level in the HC was 0.305 antibody index (A.I.), which was significantly lower than in the AAG samples with a mean level of 1.210 A.I. (p < 0.001). b) Anti-gAChRβ4 antibodies were also detected in seven samples, as shown in Fig. 4B (p = 0.005). The mean anti-gAChRβ4 antibody level in the HC was 0.367 A.I., which was significantly lower than the measn level of 0.618 A.I. in the AAG samples (p < 0.001).
Mentions: Both the anti-gAChRα3 and anti-gAChRβ4 antibodies were determined by the LIPS assay to be present in 0.0% (0 of 73) of the HC. In contrast, 48% (24 of 50) of the sera from patients with AAG were positive for autoantibodies (p < 0.001, Fig. 4A). The anti-gAChRα3 antibodies were detected in 23 samples and the anti-gAChRβ4 antibodies were detected in seven samples (14.0%), as shown in Fig. 4B (p < 0.001). Both of the antibodies were detected in six samples. The mean anti-gAChRα3 antibody levels in the HC and the DC were 0.305 A.I. and 0.336 A.I., respectively. These levels were significantly lower than the mean level in the AAG samples with a mean level of 1.210 A.I. (p < 0.001, Fig. 4A). Similarly, the mean anti-gAChRβ4 antibody level in HC was 0.367 A.I. and DC was 0.302 A.I., respectively. Those were significantly lower than the AAG samples with a mean level of 0.618 A.I. (p < 0.001, Fig. 4B). In the DC group, we detected anti-gAChRα3 antibodies in the serum of the patient with the suspected case of amyloid neuropathy.

Bottom Line: Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR.The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group.In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan; Department of Neurology, Nagasaki Kawatana Medical Center, Nagasaki, Japan.

ABSTRACT
Autoimmune autonomic ganglionopathy (AAG) is a rare acquired channelopathy that is characterized by pandysautonomia, in which autoantibodies to ganglionic nicotinic acetylcholine receptors (gAChR) may play a central role. Radioimmunoprecipitation (RIP) assays have been used for the sensitive detection of autoantibodies to gAChR in the serum of patients with AAG. Here, we developed luciferase immunoprecipitation systems (LIPS) to diagnose AAG based on IgGs to both the α3 and β4 gAChR subunits in patient serum. We reviewed the serological and clinical data of 50 Japanese patients who were diagnosed with AAG. With the LIPS testing, we detected anti-α3 and -β4 gAChR antibodies in 48% (24/50) of the patients. A gradual mode of onset was more common in the seropositive group than in the seronegative group. Patients with AAG frequently have orthostatic hypotension and upper and lower gastrointestinal tract symptoms, with or without anti-gAChR. The occurrence of autonomic symptoms was not significantly different between the seropositive and seronegative group, with the exception of achalasia in three patients from the seropositive group. In addition, we found a significant overrepresentation of autoimmune diseases in the seropositive group and endocrinological abnormalities as an occasional complication of AAG. Our results demonstrated that the LIPS assay was a useful novel tool for detecting autoantibodies against gAChR in patients with AAG.

No MeSH data available.


Related in: MedlinePlus