This study aimed to evaluate the differences in the clinical significance of antinuclear antibody (ANA) according to their titers and patterns in the diagnosis of systemic autoimmune diseases (AiD) in pediatric patients. Of the 2442 children who had undergone an ANA test, 473 (19.4%) were positive for ANA, of whom 33 (7.0%) were diagnosed with significant AiD. The positive predictive value (PPV) for significant AiD was considerably high on application of an ANA titer of ≥1:640, and the PPV of a dense fine speckled (DFS) pattern was significantly lower compared with those of speckled and homogenous patterns. The diagnostic value of ANA positivity for AiD is limited, and the clinical significance of the DFS pattern is relatively lower compared with that of other patterns, such as homogenous and speckled patterns, in children. It is necessary to approach the significance of ANA in children individually depending on titers and patterns.
SolomonDHKavanaughAJSchurPH; American College of Rheumatology Ad Hoc Committee on Immunologic Testing Guidelines. Evidence-based guidelines for the use of immunologic tests: antinuclear antibody testing. Arthritis Rheum. 2002;47(4):434-444.
2.
WonDIParkJKimBSKimCEYoonHSJungJS. Stratification of nuclear homogeneous patterns on HEp-2 cells based on neutrophil nuclear staining. Chonnam Med J. 2021;57(1):51-57.
3.
MahlerMFritzlerMJ. The clinical significance of the dense fine speckled immunofluorescence pattern on HEp-2 cells for the diagnosis of systemic autoimmune diseases. Clin Dev Immunol. 2012;2012:494356.
4.
WiikASHøier-MadsenMForslidJCharlesPMeyrowitschJ. Antinuclear antibodies: a contemporary nomenclature using HEp-2 cells. J Autoimmun. 2010;35(3):276-290.
5.
ChudwinDSAmmannAJCowanMJWaraDW. Significance of a positive anti-nuclear antibody test in a pediatric population. Am J Dis Child. 1983;137(11):1103-1106.
6.
McGheeJLKickingbirdLMJarvisJN. Clinical utility of antinuclear antibody tests in children. BMC Pediatr. 2004;4(1):13.
7.
CabralDAPettyREFungMMallesonPN. Persistent antinuclear antibodies in children without identifiable inflammatory rheumatic or autoimmune disease. Pediatrics. 1992;89(3):441-444.
8.
DeanePMLiardGSiegelDMBaumJ. The outcome of children referred to a pediatric rheumatology clinic with a positive antinuclear antibody test but without an autoimmune disease. Pediatrics. 1995;95(6):892-895.
9.
ArkachaisriTLehmanTJ. Systemic lupus erythematosus and related disorders of childhood. Curr Opin Rheumatol. 1999;11(5):384-392.
10.
LevyDMKamphuisS. Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am. 2012;59(2):345-364.
11.
HirakiLTBenselerSMTyrrellPNHebertDHarveyESilvermanED. Clinical and laboratory characteristics and long-term outcome of pediatric systemic lupus erythematosus: a longitudinal study. J Pediatr. 2008;152(4):550-556.
12.
AllenRCDewezPStuartLGatenbyPASturgessA. Antinuclear antibodies using HEp-2 cells in normal children and in children with common infections. J Paediatr Child Health. 1991;27(1):39-42.
13.
MartiniALoriniRZanaboniDRavelliABurgioRG. Frequency of autoantibodies in normal children. Am J Dis Child. 1989;143(4):493-496.
14.
WananukulSVoramethkulWKaewopasYHanvivatvongO. Prevalence of positive antinuclear antibodies in healthy children. Asian Pac J Allergy Immunol. 2005;23(2-3):153-157.
15.
PashninaIAKrivolapovaIMFedotkinaTV, et al. Antinuclear autoantibodies in health: autoimmunity is not a synonym of autoimmune disease. Antibodies (Basel). 2021;10(1):9.
16.
NiwaYSakaneTKanohTShichijoSWiederholdMDYokoyamaMM. Transient autoantibodies with elevated complement levels in common viral diseases. J Clin Lab Immunol. 1984;13(4):183-188.
17.
HargravesMMRichmondHMortonR. Presentation of two bone marrow elements: the tart cell and the LE cell. Proc Staff Meet Mayo Clin. 1948;23(2):25-28.
18.
SurLMFlocaESurDGColceriuMCSamascaGSurG. Antinuclear antibodies: marker of diagnosis and evolution in autoimmune diseases. Lab Med. 2018;49(3):e62-e73.
19.
ForslidJHeiglZJonssonJScheyniusA. The prevalence of antinuclear antibodies in healthy young persons and adults, comparing rat liver tissue sections with HEp-2 cells as antigen substrate. Clin Exp Rheumatol. 1994;12(2):137-141.
20.
Agmon-LevinNDamoiseauxJKallenbergC, et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as antinuclear antibodies. Ann Rheum Dis. 2014;73(1):17-23.
21.
MeroniPLSchurPH. ANA screening: an old test with new recommendations. Ann Rheum Dis. 2010;69(8):1420-1422.
22.
ChanEKLvon MühlenCAFritzlerMJ, et al. The international consensus on ANA patterns (ICAP) in 2021—the 6th workshop and current perspectives. J App Lab Med. 2022;7(1):322-330.
23.
AbelesAMAbelesM. The clinical utility of a positive antinuclear antibody test result. Am J Med. 2013;126(4):342-348.
24.
TanEFeltkampTSmolenJ, et al. Range of anti-nuclear antibodies in “healthy” individuals. Arthritis Rheum. 1997;40(9):1601-1611.
25.
CraigWYLedueTBJohnsonAMRitchieRF. The distribution of antinuclear antibody titers in “normal” children and adults. J Rheumatol. 1999;26(4):914-919.
26.
LiQ-ZKarpDRQuanJ, et al. Risk factors for ANA positivity in healthy persons. Arthritis Res Ther. 2011;13(2):R38.
27.
SatohMChanEKHoLA, et al. Prevalence and sociodemographic correlates of antinuclear antibodies in the United States. Arthritis Rheum. 2012;64(7):2319-2327.
28.
HilárioMOLenCARojaSCTerreriMTAlmeidaGAndradeLE. Frequency of antinuclear antibodies in healthy children and adolescents. Clin Pediatr (Phila). 2004;43(7):637-642.
29.
ArbuckleMRMcClainMTRubertoneMV, et al. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med. 2003;349(16):1526-1533.
30.
KasapcopurOOzbakirFArisoyNIngölHYaziciHOzdoğanH. Frequency of anti-nuclear antibodies and rheumatoid factor in healthy Turkish children. Turk J Pediatr. 1999;41(1):67-71.
