The Antinuclear Antibody Test in the Diagnosis of Antisynthetase Syndrome and Other Autoimmune Myopathies

Fritzler, Marvin J.; Choi, May Y.; Mähler, Michael

doi:10.3899/jrheum.170258

Cited by 17 publications

(13 citation statements)

References 19 publications

(21 reference statements)

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“…Screening for anti-NT5c1A antibodies in sIBM patients by ANA IIF will also be challenging. In keeping with many other autoantibodies described in IIM (32), anti-NT5c1A antibodies were not associated with a specific IIF staining pattern on HEp-2 cells at a 1/80 screening serum dilution. It has been suggested that the detection of some IIM-related autoantibodies can be improved by decreasing the serum dilution to 1/40 (33), although the decreased specificity at that dilution may not be an optimal approach either (32).…”

Section: Discussionsupporting

confidence: 83%

“…In keeping with many other autoantibodies described in IIM (32), anti-NT5c1A antibodies were not associated with a specific IIF staining pattern on HEp-2 cells at a 1/80 screening serum dilution. It has been suggested that the detection of some IIM-related autoantibodies can be improved by decreasing the serum dilution to 1/40 (33), although the decreased specificity at that dilution may not be an optimal approach either (32). Hence, the use of the IIF test on HEp-2 substrates as a screen for anti-NT5c1A antibodies is unlikely to be a useful serological screening test to detect the presence of these autoantibodies.…”

Section: Discussionsupporting

confidence: 83%

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Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis

et al. 2019

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Objective: Sporadic Inclusion Body Myositis (sIBM) is an inflammatory myopathy (IIM) without a specific diagnostic biomarker until autoantibodies to the cytosolic 5′-nucleotidase 1A ( NT5c1A /Mup44) were reported. The objectives of our study were to determine the sensitivity and specificity of anti-NT5c1A for sIBM, demonstrate demographic, clinical and serological predictors for anti-NT5c1A positivity and determine if anti-nuclear antibody (ANA) indirect immunofluorescence (IIF) staining on HEp-2 cells is a reliable screening method for anti-NT5c1A. Methods: Sera from sIBM patients and controls were stored at −80°C until required for analysis. IgG antibodies to NT5c1A were detected by an addressable laser bead immunoassay (ALBIA) using a full-length human recombinant protein. Autoantibodies to other autoimmune myopathy antigens (Jo-1, OJ, TIF1y, PL-12, SAE, EJ, MDA5, PL7, SRP, NXP2, MI-2) were detected by line immunoassay (LIA), chemiluminescence immunoassay (CIA) or enzyme linked immunosorbent assay (ELISA) and ANA detected by IIF on HEp-2 substrate. Demographic, clinical and serological data were obtained by chart review. Results: Forty-three patients with sIBM, 537 disease control patients with other autoimmune, degenerative and neuromuscular diseases, and 78 healthy controls were included. 48.8% (21/43) of sIBM patients were positive for anti-NT5c1A. The overall sensitivity, specificity, positive predictive value, and negative predictive value of anti-NT5c1A for sIBM were 0.49, 0.92, 0.29, and 0.96, respectively. Compared to sIBM, the frequency of anti-NT5c1A was lower in both the disease control group (8.8%, OR 0.10 [95%CI: 0.05–0.20], p < 0.0001) and in the apparently healthy control group (5.1%, OR 0.06 [95%CI: 0.02–0.18], p < 0.0001). In the univariable analysis, sIBM patients with more severe muscle weakness were more likely to be anti-NT5c1A positive (OR 4.10 [95% CI: 1.17, 14.33], p = 0.027), although this was not statistically significant (adjusted OR 4.30 [95% CI: 0.89, 20.76], p = 0.069) in the multivariable analysis. The ANA of sIBM sera did not demonstrate a consistent IIF pattern associated with anti-NT5c1A. Conclusions: Anti-NT5c1A has moderate sensitivity and high specificity for sIBM using ALBIA. The presence of anti-NT5c1A antibodies may be associated with muscle weakness. Anti-NT5c1A antibodies were not associated with a specific IIF staining pattern, hence screening using HEp-2 substrate is unlikely to be a useful predictor for presence of these autoantibodies.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 83%

Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis

et al. 2019

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“…Table 2 summarises the clinical relevance of the nine cytoplasmic HEp-2 IIFA patterns, that is, AC-15–AC-23 26 33 80–101. It is recognised that the distinction between AC-19 (dense fine speckled) and AC-20 (fine speckled) can be challenging.…”

Section: Resultsmentioning

confidence: 99%

Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective

Damoiseaux

Andrade

Carballo³

et al. 2019

Ann Rheum Dis

255

304

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The indirect immunofluorescence assay (IIFA) on HEp-2 cells is widely used for detection of antinuclear antibodies (ANA). The dichotomous outcome, negative or positive, is integrated in diagnostic and classification criteria for several systemic autoimmune diseases. However, the HEp-2 IIFA test has much more to offer: besides the titre or fluorescence intensity, it also provides fluorescence pattern(s). The latter include the nucleus and the cytoplasm of interphase cells as well as patterns associated with mitotic cells. The International Consensus on ANA Patterns (ICAP) initiative has previously reached consensus on the nomenclature and definitions of HEp-2 IIFA patterns. In the current paper, the ICAP consensus is presented on the clinical relevance of the 29 distinct HEp-2 IIFA patterns. This clinical relevance is primarily defined within the context of the suspected disease and includes recommendations for follow-up testing. The discussion includes how this information may benefit the clinicians in daily practice and how the knowledge can be used to further improve diagnostic and classification criteria.

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“…Myositis specific (MSA) and myositis associated antibodies (MAA) have been used as an aid in the diagnosis of idiopathic inflammatory myopathies (IIM) for decades [1]. Since many of the MSA (e.g., anti-synthetase antibodies), partly depending on the screening dilution, are accompanied by limited sensitivity of the indirect immunofluorescence (IIF) test on HEp-2 cells [2][3][4][5], confirmatory tests are used at screening level. At present, besides immunoprecipitation (IP), mostly line immunoassays (LIA) and dot blot (DB) assays are routinely used for the detection of MSA [6], which are convenient tools for the simultaneous detection of various antibodies, but are also accompanied by some limitations [7] including the lack of true quality controls [8], lack of sensitivity [9,10] and specificity (10) for some analytes and subjectivity in interpretation [10][11][12].…”

Section: Introductionmentioning

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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The Antinuclear Antibody Test in the Diagnosis of Antisynthetase Syndrome and Other Autoimmune Myopathies

Cited by 17 publications

References 19 publications

Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis

Anti-NT5c1A Autoantibodies as Biomarkers in Inclusion Body Myositis

Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective

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

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