Throughout their evolution, the criteria for multiple sclerosis (MS) diagnosis have relied upon clinical and paraclinical data that are supportive of MS in the absence of a better explanation (McDonald et al., 2001; Polman et al., 2011, 2005; Thompson et al., 2018). Systemic autoimmune conditions can mimic or coexist with brain, optic nerve, and spinal cord presentations of MS (Pender and Chalk, 1989; Siva, 2018). An early study reported that 13 % of patients referred for symptoms suggestive of MS were instead found to have systemic lupus erythematous (SLE), Sjogren's syndrome (SS), or antiphospholipid syndrome (APLS); it was thus proposed that all individuals with MS should be screened with serological testing to exclude an alternate diagnosis (Pender and Chalk, 1989). As such, patients referred for consideration of a MS diagnosis often undergo an extensive serologic workup including antinuclear antibody (ANA) testing (Calabrese et al., 2019), to assess for systemic autoimmune conditions that mimic MS, even when an individual already meets diagnostic criteria for MS. Since ANA is sometimes positive in people with MS as well as apparently healthy individuals (Alnajashi and Alshamrani, 2021; Barned et al., 1995; Collard et al., 1997; Pender and Chalk, 1989; Pisetsky, 2017; Tourbah et al., 1998), the utility of screening all patients undergoing workup for MS is uncertain, and routine ANA testing in those that meet formal MS diagnostic criteria has been questioned (Alnajashi and Alshamrani, 2021; Solomon et al., 2023, 2013).

Since a positive ANA has been suggested to represent systemic immune dysregulation (Barned et al., 1995; Singh, 1982), it is also possible that people with definite MS who have this marker have differences with respect to clinical phenotype of their MS. The literature is uncertain as to whether ANA serostatus is associated with clinical outcomes in MS; some studies have found no difference (Barned et al., 1995; Collard et al., 1997; Solomon et al., 2013; Tourbah et al., 1998), while one showed that progressive MS patients were more likely to be ANA positive (Singh, 1982; Spadaro et al., 1999) and another showed that a positive ANA was associated with shorter disease duration and less disability (Szmyrka-Kaczmarek et al., 2012).

The present study aims to determine if ANA seropositivity in those referred with concern for MS is more common in those who meet 2017 revised McDonald criteria compared to those who did not receive a diagnosis of MS. We also evaluated if ANA seropositivity was associated with differences in clinical or radiological phenotype in patients who received a diagnosis of MS.