Immune recognition of lysyl-tRNA synthetase and isoleucyl-tRNA synthetase by anti-OJ antibody-positive sera

Muro, Yoshinao; Yamano, Yasuhiko; Yoshida, Ken; Oto, Yohsuke; Nakajima, Kimiko; Mitsuma, Teruyuki; Kikuchi, Shiori; Matsumae, A; Ogawa‐Momohara, Mariko; Takeichi, Takuya; Kondoh, Yasuhiro; Kameyama, Masao; Todoroki, Yasuyuki; Tanaka, Yoshiya; Satoh, Minoru; Akiyama, Masashi

doi:10.1016/j.jaut.2021.102680

Cited by 20 publications

(12 citation statements)

References 45 publications

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“…As a matter of fact, 0/14 anti-OJ positive samples were detected using the most widely used LIA [ 6 ] in a comparison study with IP [ 10 ]. However, significant promise arose from a recent study showing that two components of the OJ complex [namely isoleucyl-tRNA synthetase (IARS) and lysyl-tRNA synthetase (KARS)], are likely sufficient for the effective detection of anti-OJ antibodies [ 50 ], a finding that yet has to be verified and transferred to the clinical setting. Antibodies to additional synthetases, once fully characterized [ 51 ], might help to further improve such models.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies

et al. 2021

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(1) Background: Myositis specific antibodies (MSA) represent important diagnostic and stratification tools in idiopathic inflammatory myositis (IIM) patients. Here we aimed to evaluate the clinical performance of MSA profiled by a novel particle based multi-analyte technology (PMAT) in IIM and subsets thereof. (2) Methods: 264 IIM patients and 200 controls were tested for MSA using PMAT (Inova Diagnostics, research use only). Diagnostic performance was analyzed and composite scores were generated. (3) Results: The sensitivity/specificity of the individual MSA were: 19.7%/100% (Jo-1), 7.2%/100.0% (Mi-2), 3.0%/99.0% (NXP2), 3.8%/100.0% (SAE), 2.7%/100.0% (PL-7), 1.9%/99.5 (PL-12), 1.1%/100.0% (EJ), 15.5%/99.5% (TIF1γ), 8.3%/98.5% (MDA5), 6.1%/99.0% (HMGCR) and 1.9%/98.5% (SRP). Of all IIM patients, 180/264 tested positive for at least one of the MSAs. In the individual control group, 12/200 (6.0%) tested positive for at least one MSA, most of which had levels close to the cut-off (except one SRP and one PL-12). Only 6/264 (2.3%) IIM patients were positive for more than one antibody (MDA5/HMGCR, EJ/PL-7, 2 x MDA5/TIF1γ, EJ/SAE, SAE/TIF1γ). The overall sensitivity was 68.2% paired with a specificity of 94.0%, leading to an odds ratio of 33.8. The composite scores showed good discrimination between subgroups (e.g., anti-synthetase syndrome). (4) Conclusion: MSA, especially when combined in composite scores (here measured by PMAT), provide value in stratification of patients with IIM.

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Section: Discussionmentioning

confidence: 99%

Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies

et al. 2021

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“…Since the sequence similarities between the aaRS proteins are low (Supplementary Table 3), it is unlikely that the multiple reactions are due to cross-reactivity [35, 36]. Nevertheless, studies have suggested that autoantibodies from the same individual could target several members of the multi-synthetase complex (MSC) [16, 17, 37]. Here, we found one patient, P67, with autoantibodies targeting three MSC members (ArgRS, GlnRS, and LysRS) corroborating this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…Currently, there is limited data available on the detection of these additional aaRS autoantigens. Moreover, anti-OJ autoantibodies targeting IleRS, one of the members of the intracellular multi-synthetase complex (MSC), have been suggested to potentially target several members of this complex [16, 17], which consists of eight aaRS and three scaffold proteins; aaRS complex interaction proteins (AIMP) 1, -2 and -3 [18].…”

Section: Introductionmentioning

confidence: 99%

Autoantigenic properties of the aminoacyl tRNA synthetase family in idiopathic inflammatory myopathies

Preger

Notarnicola

Hellström

et al. 2022

Preprint

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ObjectivesAutoantibodies are thought to play a key role in the pathogenesis of idiopathic inflammatory myopathies (IIM). However, up to 40% of IIM patients, even those with clinical manifestations of anti-synthetase syndrome (ASSD), test seronegative to all known myositis-specific autoantibodies (MSAs). We hypothesized the existence of new potential autoantigens among human cytoplasmic aminoacyl tRNA synthetases (aaRS) in patients with IIM.MethodsPlasma samples and clinical data from 217 patients with, 50 patients with ASSD, 165 without, and two with unknown ASSD status were included retrospectively, as well as serum from 156 age/sex-matched population controls. Samples were screened using a multiplex bead array assay for presence of autoantibodies against a panel of 118 recombinant protein variants, representing 33 myositis-related proteins, including all 19 cytoplasmic aaRS.ResultsWe identified reactivity towards 16 aaRS in 72 of the 217 patients. Twelve patients displayed reactivity against nine novel aaRS. The novel autoantibody specificities were detected in four patients previously seronegative for MSAs and in eight with previously detected MSAs. We also confirmed reactivity to four of the most common aaRS (Jo1, PL12, PL7, and EJ (n=45)) and identified patients positive for anti-Zo, -KS, and -HA (n=10) that were not previously tested. A low frequency of anti-aaRS autoantibodies was detected in controls.ConclusionOur results suggest that most, if not all, cytoplasmic aaRS may become autoantigenic. Autoantibodies against new aaRS may be found in plasma of patients previously classified as seronegative with potential high clinical relevance.

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“…This autoantibody subgroup was not assessed in our study and remains an important area for future evaluation. The detection of anti-OJ on ELISA has been reported to be problematic in the literature as there is still uncertainty regarding the best antigenic target ( 19 , 20 ). Another key MSA excluded from this analysis is anti-TIF1γ.…”

Section: Discussionmentioning

confidence: 99%

The use of ELISA is comparable to immunoprecipitation in the detection of selected myositis-specific autoantibodies in a European population

Loganathan

McMorrow

et al. 2022

Front. Immunol.

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BackgroundThe reliable detection of myositis-specific autoantibodies (MSA) provides valuable clinical information regarding prognosis, clinical progression and diagnostic confirmation.ObjectivesTo evaluate the reliability of a commercial ELISA immunoassay in detecting myositis-specific autoantibodies in comparison to immunoprecipitation as the reference standard.MethodsSerum samples were chosen from a biobank of more than 3000 samples. Samples with a confirmed MSA on Immunoprecipitation (n=116) were evaluated in duplicate by ELISA to detect Mi2, MDA5, Jo1, EJ, KS, PL-7 and PL-12 (Medical & Biological Laboratories Co. Ltd, Nagoya, Aichi, Japan). Healthy control samples (n=246) confirmed autoantibody negative by immunoprecipitation were similarly assessed.ResultsThere was a very good agreement between ELISA and immunoprecipitation for serum samples containing anti-Mi2, MDA5, Jo1, EJ, KS and PL-7 and PL-12 auto-antibodies. Cohen’s κ values ranged from 0.86-1 for the measured autoantibodies on ELISA.ConclusionELISA was an accurate method for detecting anti-synthetase, anti-Mi2 and anti-MDA5 autoantibodies.

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Immune recognition of lysyl-tRNA synthetase and isoleucyl-tRNA synthetase by anti-OJ antibody-positive sera

Cited by 20 publications

References 45 publications

Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies

Profiling of Myositis Specific Antibodies and Composite Scores as an Aid in the Differential Diagnosis of Autoimmune Myopathies

Autoantigenic properties of the aminoacyl tRNA synthetase family in idiopathic inflammatory myopathies

The use of ELISA is comparable to immunoprecipitation in the detection of selected myositis-specific autoantibodies in a European population

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