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@ARTICLE{Li:281825,
author = {Li, Lucie Y and Höltje, Markus and Rasmussen, Helle
Foverskov and Halle, Lennard and Mayrhofer, Marie and
Blüthner, Martin and Prüss, Harald},
title = {{B}inding of established antinuclear antibodies to neurons
depends on tissue fixation and underlying autoantigens.},
journal = {Frontiers in immunology},
volume = {16},
issn = {1664-3224},
address = {Lausanne},
publisher = {Frontiers Media},
reportid = {DZNE-2025-01206},
pages = {1674907},
year = {2025},
abstract = {Antinuclear antibodies (ANAs) are central biomarkers in
rheumatological conditions and can drive disease pathology.
Much less is known about the role of ANAs in neurological
symptoms, although a number of experimental studies have
demonstrated direct effects on neuronal function, for
example in neuropsychiatric lupus erythematosus. Moreover,
it is unclear whether the ANAs detected in HEp-2 cell-based
assays, the gold standard for ANA diagnostics, can also be
recognized in modern screening assays for anti-neuronal
autoimmunity, such as staining on rodent brain sections or
neuronal cultures. In this study, we therefore conducted a
comparative mapping of ANA-positive sera with
well-characterized HEp-2 patterns to central nervous system
(CNS) tissue, utilizing fixed and unfixed murine brain
sections and primary murine neurons. We screened 74
ANA-positive sera classified into 14 individual patterns and
combinations thereof. Majority of the samples reacted with
fixed primary neurons $(99\%,$ 73/74 sera), followed by
fixed brain sections $(93\%,$ 69/74), but much less to
unfixed mouse brain $(54\%,$ 40/74). While the PM/SCL- and
RPOI-positive sera showed no binding to unfixed brain
sections, the U1RNP (U1 nuclear ribonucleoprotein particle)
and FBLN (fibrillarin) ANAs reacted strongly across all
assays, indicating differences in antigen accessibility.
These findings suggest that the majority of ANAs can
interact with neural components, which may obscure the
detection of other anti-neuronal autoantibodies. The
foundational mapping of ANA binding in CNS tissue provided
here can also facilitate recognition of 'CNS-specific ANAs,'
which bind to neuronal autoantigens but not to HEp-2 cells.
Future studies should explore the association with certain
neurological manifestations and the role of ANAs in neuronal
pathology.},
keywords = {Animals / Neurons: immunology / Neurons: metabolism /
Antibodies, Antinuclear: immunology / Antibodies,
Antinuclear: metabolism / Mice / Autoantigens: immunology /
Humans / Tissue Fixation / Brain: immunology / Brain:
metabolism / Female / Male / ANA (Other) / HEp-2 (Other) /
anti-neuronal antibodies (Other) / autoimmunity (Other) /
immunofluorescence (Other) / Antibodies, Antinuclear (NLM
Chemicals) / Autoantigens (NLM Chemicals)},
cin = {AG Prüß},
ddc = {610},
cid = {I:(DE-2719)1810003},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41142797},
pmc = {pmc:PMC12549672},
doi = {10.3389/fimmu.2025.1674907},
url = {https://pub.dzne.de/record/281825},
}