Rare ANA patterns and their clinical correlates: a retrospective large-cohort study

To determine the prevalence and clinical associations of rare HEp 2 indirect immunofluorescence ANA patterns and to evaluate their relationships with disease categories, ANA titers, and expression form.

We retrospectively analyzed 366,524 ANA tests performed between 2018 and 2024 using pattern definitions based on the 2018 ICAP update. Rare patterns were defined as those occurring in less than 1 % of ANA positive cases and represented by more than 30 samples. Clinical diagnoses were categorized as autoimmune, metabolic, infectious, neoplastic, or unclassified.

Among 81,860 ANA positive cases (22.3 %), 1,769 (2.2 %) showed rare patterns. The most frequent rare patterns were AC-22 (0.7 %), AC-23 (0.41 %), AC-25 (0.25 %), AC-26 (0.23 %) and AC-29 (0.16 %). AC-29 was largely confined to autoimmune diseases, particularly systemic sclerosis, and was often observed at high titers. For AC-26, higher titers were more frequently observed among autoimmune disease cases, suggesting titer dependent enrichment. By contrast, AC-22 and AC-23 were more frequently observed in metabolic or infectious diseases and were mainly characterized by low titers (≤1:320). Cytoplasmic and mitotic patterns more commonly appeared as mixed patterns and showed broader distributions across disease categories. Among patients with systemic sclerosis exhibiting the AC-29 pattern, 96.2 % were positive for anti-Scl-70 antibodies.

Rare ANA patterns show distinct disease and titer profiles. Recognition of these patterns may enhance diagnostic accuracy when interpreted in conjunction with clinical and serological findings.