title: Toll-like receptor 2 and -4 are involved in the pathogenesis of the Guillain-Barré syndrome.
abstract: Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system characterized by weakness in the limbs. To date, numerous hypotheses have been suggested to explain the pathogenesis of GBS; however, the pathogenesis of GBS remains to be elucidated. The aim of the present study was to investigate the association between Toll-like receptor (TLR) 2, TLR4 and GBS. Therefore, the mRNA of TLR2, TLR4, myeloid differentiation factor (MyD)88 and nuclear factor (NF)-κB of peripheral blood mononuclear cells (PBMCs) in patients with GBS and healthy controls was assessed. To confirm the function of TLR2 and TLR4 in the pathogenesis of GBS, PBMCs derived from patients with GBS and healthy controls were cultured with various TLR agonists. The levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1β were measured in the culture supernatant and fasting serum was obtained for the detection of anti-ganglioside antibodies. The results revealed that the mRNA levels of TLR2, TLR4, MyD88 and NF-κB were significantly increased in patients with GBS compared with those in healthy controls (P=0.003, 0.017, 0.032 and 0.015, respectively). PBMCs from patients with GBS secreted higher levels of TNF-α and IL-1β than those from control subjects. The positive rate of immunoglobulin (Ig)G and IgM anti-ganglioside antibodies in patients with severe GBS was 42.86%, which was markedly higher than rates found in patients with mild GBS (9.09 and 18.18%, respectively). The results of the present study demonstrated that TLR2 and TLR4 are involved in the pathogenesis of GBS and that they and their associated signaling pathways may be targets for the treatment of GBS.
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Yamei
authors.initials: Y
authors.lastname: Du
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Guojun
authors.initials: G
authors.lastname: Zhang
authors.affiliation: China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Zaiqiang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Ruimin
authors.initials: R
authors.lastname: Ma
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Fan
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Youran
authors.initials: Y
authors.lastname: Li
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Lv
authors.affiliation: Laboratory Diagnosis Center, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
authors.forename: Xixiong
authors.initials: X
authors.lastname: Kang
mesh_terms: D017152:Antibodies, Antiphospholipid / Q000097:blood*; D016022:Case-Control Studies; D018450:Disease Progression; D005786:Gene Expression Regulation; D020275:Guillain-Barre Syndrome / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology; D012720:Severity of Illness Index; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics* / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
chemical_list: D017152:Antibodies, Antiphospholipid; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D053583:Interleukin-1beta; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D012333:RNA, Messenger; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha