Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis

Jacqueline Koshorek; Chen Hu; Yujie Wang; Risto Grkovski; Doris Lin; Kathryn Fitzgerald; Scott D Newsome; Ellen M Mowry

doi:10.1016/j.msard.2024.105639

Relevance of antinuclear antibody in diagnosis and characteristics of multiple sclerosis

Mult Scler Relat Disord. 2024 May 4:87:105639. doi: 10.1016/j.msard.2024.105639. Online ahead of print.

Authors

Jacqueline Koshorek¹, Chen Hu², Yujie Wang³, Risto Grkovski⁴, Doris Lin⁵, Kathryn Fitzgerald², Scott D Newsome², Ellen M Mowry²

Affiliations

¹ Department of Neurology Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jkoshorek@honorhealth.com.
² Department of Neurology Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³ Department of Neurology Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA.
⁴ Department of Radiology Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Medicine, University of Ljubljana, Ljubljana, Slovenia.
⁵ Department of Radiology Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 38704876
DOI: 10.1016/j.msard.2024.105639

Abstract

Background: Criteria for multiple sclerosis (MS) diagnosis rely upon clinical and paraclinical data that are supportive of MS in the absence of a better explanation. Patients referred for consideration of a MS diagnosis often undergo an extensive serologic workup including antinuclear antibody (ANA) testing, even when an individual already meets diagnostic criteria for MS. It is unclear whether ANA serostatus is associated with clinical outcomes in MS. The present study aims to determine if ANA seropositivity in those referred with concern for MS differs in those who meet 2017 revised McDonald criteria compared to those who did not receive a diagnosis of MS. Associations between ANA seropositivity and clinical or radiological phenotype of MS patients are also explored.

Methods: The cohort included people at least 18 years old, referred to our tertiary care MS center with concern for MS (regardless of prior diagnosis) who had an ANA test with known titer completed within one year of first evaluation. Electronic health record (EHR) charts were manually reviewed, and MRIs underwent blinded review by a radiologist with training in neuroradiology. Diagnosis of MS was determined by a neuroimmunologist and was based on 2017 revised McDonald Criteria. Results are reported as odds ratios from multivariable logistic regression analyses adjusted for age, sex at birth, race, smoking history, personal history of comorbid autoimmune conditions, and family history of autoimmunity. Within the MS cohort, similar analytical models were performed to assess association between ANA and clinical and radiological characteristics.

Results: A final cohort of 258 patients was analyzed (out of 542 referrals): 106 nonMS and 152 with MS. There was no association between MS (vs. nonMS) diagnosis and ANA status (ANA positive n = 74) in the multivariable models (OR 1.5, 95 % CI 0.82, 2.72, p = 0.20). Among those with MS, there was no association of ANA seropositivity with the odds of atypical brain MRI features, number of cardinal MRI areas involved, location of MRI lesions, or of having an atypical presentation of first demyelinating event. Black race (OR 2.8, 95 % CI 1.27, 6.26, p = 0.01) and family history of autoimmunity (OR 2.1, 95 % CI 1.09, 3.98, p = 0.03) were independently associated with increased odds of ANA positivity. Within the MS cohort analysis, progressive MS (PMS; vs relapsing-remitting MS), a covariate in the model, appeared to be at higher odds of being ANA positive (OR 3.6, 95 % CI 1.03, 13.05, p = 0.046) but only when assessing mean area of cardinal MS locations.

Conclusions: While ANA testing does not appear to be useful in distinguishing MS from non-MS, it remains less clear as to whether it may be associated with differences in the clinical course of MS (relapsing-remitting vs progressive). Future studies should aim to systematically evaluate whether those who are ANA positive are more likely, in well-designed and representative prospective cohorts, to be diagnosed with or develop progressive MS. Whether a positive ANA early in MS is associated with increased risk over time of developing or diagnosing another systemic autoimmune disease would also be of interest.

Keywords: Antinuclear Antibody (ANA); Multiple sclerosis; Prognostic factors.