Uncommon patterns of antinuclear antibodies recognizing mitotic spindle apparatus antigens and clinical associations

Betancur, Juan Felipe; Londoño, A; Estrada, Victoria Eugenia; Puerta, Sandra Liliana; Osorno, S.M.; Loaiza, Angela; Carmona, Jenny Andrea; Gómez-Puerta, José A.

doi:10.1097/md.0000000000011727

Cited by 15 publications

(14 citation statements)

References 35 publications

(50 reference statements)

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“…Even though the work of Betancur et al aimed to have a prospective correlational design and included a large number of subjects (113, 491), a retrospective design was used, with limited or no access to all clinical data, and it was not clear how geographical and racial differences in the prevalence of rare ANA patterns were balanced [ 41 ]. A possibility of misclassification exists, as a specialist was not always involved in the diagnostic process.…”

Section: Resultsmentioning

confidence: 99%

Biomarkers for Inner Ear Disorders: Scoping Review on the Role of Biomarkers in Hearing and Balance Disorders

et al. 2020

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The diagnostics of inner ear diseases are primarily functional, but there is a growing interest in inner ear biomarkers. The present scoping review aimed to elucidate gaps in the literature regarding the definition, classification system, and an overview of the potential uses of inner ear biomarkers. Relevant biomarkers were categorized, and their possible benefits were evaluated. The databases OVID Medline, EMBASE, EBSCO COINAHL, CA PLUS, WOS BIOSIS, WOS Core Collection, Proquest Dissertations, Theses Global, PROSPERO, Cochrane Library, and BASE were searched using the keywords “biomarker” and “inner ear”. Of the initially identified 1502 studies, 34 met the inclusion criteria. The identified biomarkers were classified into diagnostic, prognostic, therapeutic, and pathognomonic; many were detected only in the inner ear or temporal bone. The inner-ear-specific biomarkers detected in peripheral blood included otolin-1, prestin, and matrilin-1. Various serum antibodies correlated with inner ear diseases (e.g., anti-type II collagen, antinuclear antibodies, antibodies against cytomegalovirus). Further studies are advised to elucidate the clinical significance and diagnostic or prognostic usage of peripheral biomarkers for inner ear disorders, filling in the literature gaps with biomarkers pertinent to the otology clinical practice and integrating functional and molecular biomarkers. These may be the building blocks toward a well-structured guideline for diagnosing and managing some audio-vestibular disorders.

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Section: Resultsmentioning

confidence: 99%

Biomarkers for Inner Ear Disorders: Scoping Review on the Role of Biomarkers in Hearing and Balance Disorders

et al. 2020

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“…NuMA/ centrophilin is an abundant 236 kDa protein, which plays a critical role in mitotic spindle formation, chromosome separation, and nuclear reassembly [31]. Although anti-NuMA has an estimated prevalence of <1% among sera screened for HEp-2 IFA [31][32][33][34], it has strong clinical associations with systemic autoimmune diseases. Anti-NuMA autoantibodies are more commonly associated with SjS and SLE, but may also be present in patients with rheumatoid arthritis (RA), undifferentiated connective tissue disease, mixed connective tissue disease, and in nonautoimmune conditions such as infections or malignancies [31,34].…”

Section: Introductionmentioning

confidence: 99%

“…Although anti-NuMA has an estimated prevalence of <1% among sera screened for HEp-2 IFA [31][32][33][34], it has strong clinical associations with systemic autoimmune diseases. Anti-NuMA autoantibodies are more commonly associated with SjS and SLE, but may also be present in patients with rheumatoid arthritis (RA), undifferentiated connective tissue disease, mixed connective tissue disease, and in nonautoimmune conditions such as infections or malignancies [31,34]. Although AC-6, AC-18, and AC-26 patterns are among the lower prevalent AC patterns in populations studied and ICAP has classified these patterns at the "expert reporting level"more challenging and reportable only when observers or technologists have attained the experiencethere is a critical need to have reliable and accessible reference materials to facilitate identification of these patterns.…”

Section: Introductionmentioning

confidence: 99%

Establishment of international autoantibody reference standards for the detection of autoantibodies directed against PML bodies, GW bodies, and NuMA protein

Zheng

Mora

Fritzler

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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ObjectivesReference materials are important in the standardization of autoantibody testing and only a few are freely available for many known autoantibodies. Our goal was to develop three reference materials for antibodies to PML bodies/multiple nuclear dots (MND), antibodies to GW bodies (GWB), and antibodies to the nuclear mitotic apparatus (NuMA).MethodsReference materials for identifying autoantibodies to MND (MND-REF), GWB (GWB-REF), and NuMA (NuMA-REF) were obtained from three donors and validated independently by seven laboratories. The sera were characterized using indirect immunofluorescence assay (IFA) on HEp-2 cell substrates including two-color immunofluorescence using antigen-specific markers, western blot (WB), immunoprecipitation (IP), line immunoassay (LIA), addressable laser bead immunoassay (ALBIA), enzyme-linked immunosorbent assay (ELISA), and immunoprecipitation–mass spectrometry (IP-MS).ResultsMND-REF stained 6–20 discrete nuclear dots that colocalized with PML bodies. Antibodies to Sp100 and PML were detected by LIA and antibodies to Sp100 were also detected by ELISA. GWB-REF stained discrete cytoplasmic dots in interphase cells, which were confirmed to be GWB using two-color immunofluorescence. Anti-Ge-1 antibodies were identified in GWB-REF by ALBIA, IP, and IP-MS. All reference materials produced patterns at dilutions of 1:160 or greater. NuMA-REF produced fine speckled nuclear staining in interphase cells and staining of spindle fibers and spindle poles. The presence of antibodies to NuMA was verified by IP, WB, ALBIA, and IP-MS.ConclusionsMND-REF, GWB-REF, and NuMA-REF are suitable reference materials for the corresponding antinuclear antibodies staining patterns and will be accessible to qualified laboratories.

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“…This harmonisation is crucial in eventually finding clinical associations of rare patterns. The original study of Betancur et al ,7 unfortunately, does not follow the international consensus. While nuclear and cytoplasmic patterns are equally identified, Betancur et al utilise a cell-cycle related or mitotic spindle apparatus (MSA) category instead of mitotic patterns.…”

mentioning

confidence: 99%

Response to: ‘Antinuclear antibodies: mitotic patterns and their clinical associations’ by Betancur and Gómez-Puerta

Damoiseaux

Andrade

2019

Ann Rheum Dis

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Uncommon patterns of antinuclear antibodies recognizing mitotic spindle apparatus antigens and clinical associations

Abstract: Supplemental Digital Content is available in the text

Cited by 15 publications

References 35 publications

Biomarkers for Inner Ear Disorders: Scoping Review on the Role of Biomarkers in Hearing and Balance Disorders

Biomarkers for Inner Ear Disorders: Scoping Review on the Role of Biomarkers in Hearing and Balance Disorders

Establishment of international autoantibody reference standards for the detection of autoantibodies directed against PML bodies, GW bodies, and NuMA protein

Response to: ‘Antinuclear antibodies: mitotic patterns and their clinical associations’ by Betancur and Gómez-Puerta

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