Background/Purpose: The idiopathic inflammatory myopathies (IIMs) are a heterogeneous group of autoimmune connective tissue diseases that often present with multisystem involvement. Autoantibodies such as myositis-specific autoantibodies (MSA) and myositis-associated autoantibodies (MAA) can now be identified in up to 70% of IIM patients. Clinical validation of multi-specific immunoassays, especially regarding the clinical relevance of low-titer positive MSA/MAA in the setting of a malignancy, remains to be determined.

Methods: Using an electronic database, we identified all patients for whom a myositis panel was assessed through the Eastern Ontario Regional Laboratory Association from June 2019 to October 2024. This myositis panel included 18 autoantibodies detected by a semi-quantitative (autoantibodies are reported in terms of low, moderate and high titers) immunoblot assay (EUROIMMUN Medizinische Labordiagnostika AG, Lübeck Germany). We performed a retrospective chart review examining clinical characteristics of the subset of patients with low titers of MSA/MAA and a history of malignancy.

Results: We identified 166 patients with low titer positive MSA or MAA antibodies from 1478 patients with a myositis panel result. In total, 38 patients had a history of malignancy and 7 patients (18%) were clinically true positives, meaning their positive MSA/MAA was clinically associated with a diagnosis of IIM [Table 1]. IIM diagnoses included cancer-associated (n=2), amyopathic dermatomyositis (n=1), dermatomyositis (n=2), antisynthetase syndrome (n=1), and immune mediated necrotizing myopathy (n=1). The majority (58%) of underlying malignancies in clinically false positives (n=31) were gastrointestinal (n=5), skin (n=7) and breast (n=6). Proximal weakness was present in 71% of clinically true positive cases, whereas interstitial lung disease presented most commonly (32%) among those with clinically false positives [Table 2]. A large proportion of clinically false positives were found to be anti-Mi2-alpha (3%) or -beta (19%) positive, anti-PL7 positive (23%), or anti-NXP2 positive (13%) [Table 3]. From the 11 patients (29%) identified with multiple positive MSA/MAA, 2 had clinically true positives.

Conclusion: In patients with an underlying malignancy, a positive MSA/MAA at low titer identified by multi-specific immunoassay had a corresponding clinical positive in only 18% (n=7/38) of cases, and 18% (n=2/11) of those with multiple positive MSA/MAA. The most common false positives identified were anti-Mi2-beta (19%), anti-PL7 (23%) and anti-NXP2 (13%). Further studies are needed to understand the clinical significance of low positive titer MSA/MAA in the setting of a past or present malignancy.

Table 1 | Demographics

Table 2 | Clinical Characteristics

Table 3 | Antibody Profile

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-relevance-of-low-titer-positive-myositis-specific-autoantibodies-and-myositis-associated-autoantibodies-in-patients-with-an-underlying-malignancy/