Uncommon patterns of antinuclear antibodies recognizing mitotic spindle apparatus antigens and clinical associations

Antinuclear antibodies (ANA) are key biomarkers in the evaluation of rheumatic diseases. The prevalence and clinical significance of uncommon or rare patterns, particularly those directed at the mitotic spindle apparatus (MSA), are not well understood. We aimed to investigate the prevalence and clinical significance of anti-MSA patterns in a Colombian population. During 2013 and 2014, 113,491 consecutive determinations of ANA were studied for the presence of uncommon patterns. Clinical and laboratory data of anti-MSA positive patients were retrospectively collected and analyzed. Of the 113,491 patients tested, 60,501 (53%) were positive for ANA, of which 834 (1.3%) were positive for uncommon/rare patterns of ANA (anti-MSA in 592 cases). Of these 592 cases, complete data were available in 329 patients, of whom 116 had an established diagnosis. Anti-MSA antibodies were the only ANA positive test in 81% patients. At least one fine reactivity was identified in 19/116 (16.3%) of ANA-positive patients, of which anti-Ro was the most prevalent (18/116, 15.5%). The most frequent patterns were nuclear mitotic apparatus (NuMA) (56%) and MSA-2 (25%). The NuMA pattern had the highest ANA titers: mean 320 (range 80–2560) and behaved as monospecific antibodies. The most frequent systemic autoimmune diseases were Sjögren syndrome (SS) (18.1%), rheumatoid arthritis (RA) (13.8%), and systemic lupus erythematosus (SLE) (11%). Undifferentiated connective tissue disease (UCTD) was associated with the centrosome (P < .001), NuMA (P < .02) and MSA-2 (P < .45) patterns. Chronic idiopathic urticaria (CIU) was associated with the NuMA pattern (P < .02) and sensorineural hearing loss (SNHL) was associated with the MSA-2 (P < .001), centrosome (P < .68) and CENP-F (P < .38) patterns, previously unreported findings. Malignancies were found in 8 patients (50% were papillary thyroid cancer). In a large cohort of ANA determinations, uncommon patterns were found in around 1% of cases. The most frequent anti-MSA patterns found were NuMA and MSA-2. More than 50% of patients with anti-MSA had an associated CTD, mainly SS, RA and SLE, and anti-MSA behaved as monospecific antibodies. Other entities of presumed autoimmune origin, like CIU and SNHL, might be associated with these patterns. Abbreviations: ACR = American College of Rheumatology, AIED = autoimmune inner ear disease, ANA = antinuclear antibodies, ANCA = antineutrophil cytoplasmatic antibodies, anti-CCP = anticyclic citrullinated peptide, anti-dsDNA = anti-double-stranded DNA, aPL = antiphospholipid antibodies, APS = antiphospholipid syndrome, CIU = chronic idiopathic urticaria, CTD = connective tissue disease, ENA = antiextractable nuclear antigen antibodies, EULAR = European League Against Rheumatism, ICAP = International Consensus on ANA Pattern, IIF = indirect immunofluorescence, MCTD = mixed connective tissue disease, MD = Meniere’s disease, MSA = mitotic spindle apparatus, NuMA = nuclear mitotic apparatus, PCNA = proliferating cell nuclear antigen, RA = rheumatoid arthritis, RF = rheumatoid factor, RNP = ribonucleoprotein, SLE = systemic lupus erythematosus, SNHL = sensorineural hearing loss, SS = Sjögren syndrome, SSc = systemic sclerosis, UCTD = undifferentiated connective tissue disease.