Evidence map›Paper›PMID 33773096›Full record

ArticleJournal of cachexia, sarcopenia and muscle2021

Autoantibody of NRIP, a novel AChR-interacting protein, plays a detrimental role in myasthenia gravis.

Li-Kai Tsai, I-Hsin Chen, Chi-Chao Chao, Hsueh-Wen Hsueh, Hsin-Hsiung Chen, Yun-Hsin Huang, Rong-Wei Weng, Tzu-Yun Lai, Yi-Chieh Tsai, Yeou-Ping Tsao and 1 more

Registry-linked trialOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cachexia, sarcopenia and muscle, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07726563 (Plasmapheresis in Amyotrophic Lateral Sclerosis With Autoantibody Against NRIP 2), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 35% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT07726563 narecruitingnot on this mapstarted 2026, after this paper: background citation

Plasmapheresis in Amyotrophic Lateral Sclerosis With Autoantibody Against NRIP 2 (PALADIN2)

TypeinterventionalSponsorNational Taiwan University HospitalRan2026 to 2029Enrolled20ConditionsAmyotrophic Lateral Sclerosis (ALS), Autoantibody, PlasmapheresisArmsplasmapheresis
3 · Its place in the literature

Who cites it

5 citing papers in PubMed, 4 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 3 institutions in 1 country.

Li-Kai TsaiDepartment of Neurology, National Taiwan University Hospital, Taipei, Taiwan.ORCID 0000-0001-8420-6951
I-Hsin ChenGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Chi-Chao ChaoDepartment of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Hsueh-Wen HsuehDepartment of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Hsin-Hsiung ChenGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yun-Hsin HuangGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Rong-Wei WengGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Tzu-Yun LaiGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Yi-Chieh TsaiDepartment of Neurology, National Taiwan University Hospital, Taipei, Taiwan.
Yeou-Ping TsaoDepartment of Ophthalmology, Mackay Memorial Hospital, Taipei, Taiwan.
Show-Li ChenGraduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
National Taiwan University · TWNational Taiwan University Hospital · TWMackay Memorial Hospital · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundNuclear receptor interaction protein (NRIP) co-localizes with acetylcholine receptor (AChR) at the neuromuscular junction (NMJ), and NRIP deficiency causes aberrant NMJ architecture. However, the normal physiological and pathophysiological roles of NRIP in NMJ are still unclear.

methodsWe investigated the co-localization and interaction of NRIP with AChR-associated proteins using immunofluorescence and immunoprecipitation assay, respectively. The binding affinity of AChR-associated proteins was analysed in muscle-restricted NRIP knockout mice and NRIP knockout muscle cells (C2C12). We further collected the sera from 43 patients with myasthenia gravis (MG), an NMJ disorder. The existence and features of anti-NRIP autoantibody in sera were studied using Western blot and epitope mapping.

resultsNRIP co-localized with AChR, rapsyn and α-actinin 2 (ACTN2) in gastrocnemius muscles of mice; and α-bungarotoxin (BTX) pull-down assay revealed NRIP with rapsyn and ACTN2 in complexes from muscle tissues and cells. NRIP directly binds with α subunit of AChR (AChRα) in vitro and in vivo to affect the binding affinity of AChR with rapsyn and rapsyn with ACTN2. In 43 patients with MG (age, 58.4 ± 14.5 years; female, 55.8%), we detected six of them (14.0%) having anti-NRIP autoantibody. The presence of anti-NRIP autoantibody correlated with a more severe type of MG when AChR autoantibody existed (P = 0.011). The higher the titre of anti-NRIP autoantibody, the more severe MG severity (P = 0.032). The main immunogenic region is likely on the IQ motif of NRIP. We also showed the IgG subclass of anti-NRIP autoantibody mainly to be IgG1.

conclusionsNRIP is a novel AChRα binding protein and involves structural NMJ formation, which acts as a scaffold to stabilize AChR-rapsyn-ACTN2 complexes. Anti-NRIP autoantibody is a novel autoantibody in MG and plays a detrimental role in MG with the coexistence of anti-AChR autoantibody.

Indexed as

AcetylcholineMyasthenia GravisAnimalsFemaleHumansMiceMuscle, SkeletalNeuromuscular JunctionReceptors, CholinergicAcetylcholineReceptors, CholinergicAutoantibody; Acetylcholine receptor; Myasthenia gravis; Neuromuscular junction; Nuclear receptor interaction protein

Identifiers

PMID33773096
PMCPMC8200423
OpenAlexW3147907850

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.