Abstract | BACKGROUND: METHODS: Patients with IBS met Rome III criteria were enrolled. Controls included healthy subjects (HS) and patients with slow transit functional constipation, inflammatory bowel disease, chronic intestinal pseudo-obstruction, and autoimmune diseases. Indirect immunofluorescence was used to detect AENA. Anti-enteric neuronal antibodies intensities were termed as "1" = weak fluorescence (mild positive); "2" = moderate fluorescence (moderate positive); "3" = very high fluorescence (intensive positive). Intensities of ≥1 were defined as positive and ≥2 were defined as obvious positive. Cultured myenteric neurons of small intestine from guinea pigs and human SH-Sy5Y cells were incubated with fetal bovine serum (FBS), HS sera, or IBS sera with or without AENA. Indirect immunofluorescence with anti-PGP9.5/ DAPI/anti-active caspase-3 or TUNEL, Western blot, and flow cytometry were used to detect apoptosis. KEY RESULTS: Overall, 293 patients with IBS were enrolled (41.7 ± 11.5 years). AENA-positive and obvious positive rates in IBS were higher than HS (76.8% vs 33%; 43.7% vs 7%; all P < 0.001). Myenteric neurons incubated with AENA moderate or intensive positive IBS sera showed higher rates of anti-active caspase-3 and TUNEL-positive cells than HS or FBS (20% ± 7.3% and 35% ± 13.3% vs 4.3% ± 1.5% and 0.9% ± 0.4%, respectively; 6.2% ± 2.0% and 10.2% ± 4.6% vs 1.3% ± 1.9% and 0.5%±0.5%, respectively; all P < 0.05). Human SH-Sy5Y cells incubated with AENA moderate or intensive positive IBS sera showed increased cleaved caspase-3 and Bax expression and decreased Bcl-2 expression. Flow cytometry showed apoptosis rates of these two groups were higher than that of AENA mild positive, negative, HS, and FBS (7.6%±0.8% and 10.7%±1.3% vs 5.0%±0.8%, 3.8%±0.3%, 3.4%±0.2% and, 2.8%±0.2%, P < 0.05). CONCLUSIONS AND INFERENCES: The AENA obvious positive rate in patients with IBS was higher than HS, and sera with higher levels of AENA promoted neuronal apoptosis. AENA-mediated neuropathy might exist in a subset of patients with IBS.
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Authors | Wenjuan Fan, Guijun Fei, Xiaoqing Li, Xiyu Wang, Chaojun Hu, Haiwei Xin, Xiaohong Sun, Yongzhe Li, Jackie D Wood, Xiucai Fang |
Journal | Neurogastroenterology and motility
(Neurogastroenterol Motil)
Vol. 30
Issue 12
Pg. e13457
(12 2018)
ISSN: 1365-2982 [Electronic] England |
PMID | 30230140
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2018 The Authors Neurogastroenterology & Motility Published by John Wiley & Sons, Ltd. |
Chemical References |
- Autoantibodies
- Autoantigens
|
Topics |
- Adult
- Animals
- Apoptosis
(immunology)
- Autoantibodies
(blood)
- Autoantigens
(immunology)
- Female
- Guinea Pigs
- Humans
- Irritable Bowel Syndrome
(blood, immunology)
- Male
- Middle Aged
- Myenteric Plexus
(immunology)
- Neurons
(immunology)
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