Abstract
Nucleolar staining is one of the standard patterns in immunofluorescence antinuclear antibodies (ANA), seen in 5–9% of ANA in various conditions. Antinucleolar antibodies (ANoA) are classified into 3 patterns in the International Consensus on ANA Patterns (ICAP) classification; AC-8 homogeneous pattern, AC-9 clumpy pattern, and AC-10 punctate pattern. Specificities known to show AC-8 include anti-Th/To, -PM-Scl, -nucleophosmin/B23, -nucleolin/C23, -No55, and others. AC-9 is seen by anti-fibrillarin/U3RNP and AC-10 by anti-RNA polymerase I and hUBF/NOR-90. ANoA has been classically known to be associated with scleroderma (SSc) and the characterization of nucleolar antigens identified several autoantigens recognized by SSc autoantibodies. The clinical association of anti-Th/To, PM-Scl, fibrillarin/U3RNP, and RNA polymerase I with SSc or SSc-overlap syndrome is well established, and commercial assays are developed. Anti-hUBF/NOR90, nucleophosmin/B23, and nucleolin/C23 are known for decades and reported in systemic autoimmune rheumatic diseases (SARDs), malignancies, graft versus host disease (GVHD), and others; however, their clinical significance remains to be established.
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Abbreviations
- ACA:
-
Anticentromere antibodies
- AFP:
-
Alpha fetoprotein
- AH:
-
Autoimmune hepatitis
- ALCL:
-
Anaplastic large cell lymphoma
- ALK:
-
Anaplastic lymphoma kinase
- AMA:
-
Anti-mitochondria antibodies
- ANA:
-
Antinuclear antibodies
- ANoA:
-
Antinucleolar antibodies
- APS:
-
Antiphospholipid syndrome
- BC:
-
Breast cancer
- BMT:
-
Bone marrow transplant
- BPH:
-
Benign prostatic hypertrophy
- CADM:
-
Clinically amyopathic dermatomyositis
- cGVHD:
-
Chronic graft versus host disease
- CH:
-
Chronic hepatitis
- CI:
-
Confidence interval
- CIA:
-
Chemiluminescence immunoassay
- CL:
-
Cardiolipin
- CLD:
-
Chronic liver disease
- CTDs:
-
Connective tissue diseases
- CTNE:
-
Calf thymus nuclear extract
- dcSSc:
-
Diffuse cutaneous SSc
- DB:
-
Dot blot
- DID:
-
Double immunodiffusion
- DLE:
-
Discoid lupus erythematosus
- DM:
-
Dermatomyositis
- ELISA:
-
Enzyme-linked immunosorbent assay
- ENA:
-
Extractable nuclear antigen
- GAVE:
-
Gastric antral vascular ectasia
- GVHD:
-
Graft versus host disease
- HCC:
-
Hepatocellular carcinoma
- HR:
-
Hazard ratio
- hUBF:
-
Human upstream binding factor
- ICAP:
-
International Consensus on Antinuclear Antibody Patterns
- IIF:
-
Indirect immunofluorescence
- IIM:
-
Idiopathic inflammatory myopathy
- ILD:
-
Interstitial lung disease
- IP:
-
Immunoprecipitation
- IP-NB:
-
Immunoprecipitation-northern blot
- IPF:
-
Idiopathic pulmonary fibrosis
- ITP:
-
Idiopathic thrombocytopenic purpura
- lcSSc:
-
Limited cutaneous SSc
- LC:
-
Liver cirrhosis
- LIA:
-
Line immunoassay
- mAbs:
-
Monoclonal antibodies
- MCTD:
-
Mixed connective tissue disease
- NCM:
-
Nailfold capillary microscopy
- NHANES:
-
National Health and Nutrition Examination Survey
- NHC:
-
Normal human controls
- NHS:
-
Normal human serum
- NOR:
-
Nucleolar organizer regions
- NPM:
-
Nucleophosmin
- NSCLC:
-
Non-small cell lung cancer
- OA:
-
Osteoarthritis
- OL:
-
Overlap syndrome
- PAH:
-
Pulmonary arterial hypertension
- PCa:
-
Prostatic carcinoma
- PH:
-
Pulmonary hypertension
- PM:
-
Polymyositis
- PMR:
-
Polymyalgia rheumatica
- PSA:
-
Prostate-specific antigen
- RA:
-
Rheumatoid arthritis
- RD:
-
Rheumatic diseases
- RHA II:
-
Nucleolar RNA helicase II
- RIA:
-
Radioimmunoassay
- RNAP:
-
RNA polymerases
- RNP:
-
Ribonucleoproteins
- RP:
-
Raynaud’s phenomenon
- SARDs:
-
Systemic autoimmune rheumatic diseases
- SclMy:
-
Scleromyositis
- SjS:
-
Sjӧgren’s syndrome
- SLE:
-
Systemic lupus erythematosus
- snoRNP:
-
Small nucleolar RNP
- SRC:
-
Scleroderma renal crisis
- SRD:
-
Systemic rheumatic diseases
- SSc:
-
Scleroderma, systemic sclerosis
- ssSSc:
-
Systemic sclerosis sine scleroderma
- TCAD:
-
Transplant-related coronary disease
- TnT:
-
In vitro transcription and translation
- TSS:
-
Total skin score
- UCTD:
-
Undifferentiated connective tissue disease
- WB mice:
-
(NZW × BXSB) F1 mice
- WB:
-
Western blot
- β2GPI:
-
Beta2 glycoprotein I
- 2D-WB:
-
Two-dimensional western blot
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This work was supported by JSPS KAKENHI (Grants-in-Aid for Scientific Research) grant number 19K08617 (for MS).
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Satoh, M., Ceribelli, A., Hasegawa, T. et al. Clinical Significance of Antinucleolar Antibodies: Biomarkers for Autoimmune Diseases, Malignancies, and others. Clinic Rev Allerg Immunol 63, 210–239 (2022). https://doi.org/10.1007/s12016-022-08931-3
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DOI: https://doi.org/10.1007/s12016-022-08931-3