Anti-Myxovirus Resistance Protein 1: A Novel Biomarker for Autoimmune Myositis and Interstitial Lung Disease in Systemic Lupus Erythematosus

Eugene Krustev¹, Marvin Fritzler², Sasha Bernatsky³, Yvan St-Pierre⁴, Evelyne Vinet⁵, Christian Pineau⁶, Arielle Mendel⁷, Faras Kalache⁸, Louis-Pierre Grenier⁸, Thaisa Cotton⁸, Omid Zahedi⁹ and May Choi¹, ¹University of Calgary, Calgary, AB, Canada, ²Mitogen Diagnostics Corp, Calgary, AB, Canada, ³Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ⁴McGill University Health Center, Montreal, QC, Canada, ⁵McGill University Health Centre, Montreal, QC, Canada, ⁶McGill University, Montreal, QC, Canada, ⁷Division of Rheumatology, Department of Medicine, McGill University and Centre for Outcomes Research and Evaluation, McGill University Health Centre, Montreal, QC, Canada, ⁸Division of Rheumatology, Department of Medicine, McGill University, Montreal, QC, Canada, ⁹Division of Rheumatology, Department of Medicine, University of Alberta Hospital, Edmonton, AB, Canada

Meeting: ACR Convergence 2024

Keywords: Autoantibody(ies), Biomarkers, interstitial lung disease, Myositis, Systemic lupus erythematosus (SLE)

Session Information

Date: Saturday, November 16, 2024

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster I

Session Type: Poster Session A

Session Time: 10:30AM-12:30PM

Background/Purpose: Although autoimmune myositis (AIM) and interstitial lung disease (ILD) are uncommon in systemic lupus erythematosus (SLE), they are associated with worse outcomes. Myxovirus Resistance Protein 1 (MxA), is a type I interferon-induced GTPase that is sarcoplasm-expressed in muscle biopsies from patients with dermatomyositis and SLE-associated AIM [1]. Autoantibodies against MxA (anti-MxA) are expressed in idiopathic interstitial pneumonia [2]. We assessed the frequency of anti-MxA autoantibodies in SLE patients with AIM and/or ILD, and compared the diagnostic performance of anti-MxA to previously the identified biomarkers for SLE-associated AIM and ILD.

Methods: McGill Lupus Cohort participants (N=551, 2000-2017) without a history of AIM and/or ILD, meeting the 1997 American College of Rheumatology criteria [3], were followed at annual study visits from cohort enrolment until either the date of AIM and/or ILD diagnosis or December 31, 2017. A case-cohort analysis was performed, comparing all patients who developed AIM and/or ILD on follow-up with a randomly selected sub-cohort of SLE patients (N = 72). To determine how anti-MxA compares to previously identified biomarkers in this SLE cohort, we tested for anti-MxA by addressable laser bead immunoassay using full-length human recombinant protein on: 1) baseline samples (first visit starting from January 2000 or enrollment if after this date) and 2) one follow-up sample (randomly selected between baseline and end of follow-up). Follow-up ended at date of AIM and/or ILD diagnosis or death or last date seen or December 31, 2017, whichever came first.

Results: At baseline, there was a greater proportion of anti-MxA positivity among individuals with SLE who later developed AIM and/or ILD compared to those who did not (46.2% vs. 9.7%, respectively) (Figure 1A). Baseline anti-MxA titres were increased in individuals who later developed AIM and/or ILD compared to those who did not (Figure 1B). Considering anti-MxA autoantibodies assessed at baseline and follow-up, almost all AIM and/or ILD cases (12/13, 92.3%) were anti-MxA positive during their disease course (ILD alone 7/8, 87.5%; AIM alone 3/3, 100%; AIM and ILD 2/2, 100%;), while only 11.1% (8/72) of SLE patients without AIM or ILD expressed anti-MxA (Figure 2A). Anti-MxA positivity had high sensitivity (92.3%; 95% CI: 64.0%, 99.8%) and specificity (88.9%; 95% CI: 79.3%, 95.1%) for AIM and/or ILD, with a receiver-operating-characteristic area under the curve (ROC AUC) of 0.91 (95% CI: 0.83, 0.98), which outperformed the ROC AUC for previously identified biomarkers KL-6 (0.63; 95% CI: 0.52, 0.80), anti-Ku (0.57; 95% CI: 0.47, 0.67), and anti-Ro52/TRIM21 (0.62; 95% CI: 0.47,0.77) (Figure 2B).

Conclusion: These results suggest anti-MxA is an important biomarker for AIM and ILD in SLE. Anti-MxA outperformed previously identified biomarkers. A larger study is underway to confirm these findings and examine associations with other SLE features and in other connective tissue diseases.

References:
[1] Xing C, et al., Muscle Nerve. 2024; 69(5): 548-555.
[2] Hamano, Y., et al., Scientific Reports 2017; 7(1): 43201.
[3] Hochberg MC., Arthritis Rheum 1997; 40: 1725.

Figure 1: Baseline anti-MxA expression was predictive of the development of AIM and ILD in SLE (N= 551). A) Baseline anti-MxA expression was significantly more prevalent in SLE patients who developed AIM and/or ILD when compared those who did not develop AIM/ILD (46.2% vs. 9.7%,). B) Median baseline anti-MxA titres tended to be higher in SLE patient with AIM and/or ILD (161.0 MFU, IQR 108.0, 255.0) when compared to those who did not develop AIM/ILD (82.8 MFU, IQR, 64.3, 120.0). AIM, autoimmune myositis, ILD, interstitial lung disease; IQR, interquartile range; MxA, myxovirus resistance protein 1.

Figure 2: Anti-MxA expression studied over the disease course was highly associated with the development of AIM and ILD in SLE (N= 551). A) Almost all patients (12/13, 92.3%) who developed AIM and/or ILD were anti-MxA positive during their disease course (ILD alone 7/8, 87.5%; AIM alone 3/3, 100%; AIM and ILD 2/2, 100%), while only 11.1% (8/72) of SLE patients who did not develop AIM and/or ILD expressed anti-MxA. B) The receiver-operating-characteristic area under the curve (ROC AUC) for predicting the development of AIM and/or ILD for anti-MxA was 0.91 (95% CI: 0.83, 0.98), which was significantly higher than the ROC AUC for KL-6 (0.63 [95% CI: 0.52, 0.80]), anti-Ku (0.57 [95% CI: 0.47, 0.67]), and anti-Ro52/TRIM21 (0.62 [95% CI: 0.47,0.77]). AIM, autoimmune myositis, ILD, interstitial lung disease; KL-6, Krebs von den Lungen-6; MxA, myxovirus resistance protein 1; Ro52/TRIM21, Ro52/Tripartite motif containing_21.

Disclosures: E. Krustev: None; M. Fritzler: Mitogen Diagnostics Corporation, 8, 12, Medical Director, Werfen, 1, 2, 6; S. Bernatsky: None; Y. St-Pierre: None; E. Vinet: None; C. Pineau: None; A. Mendel: None; F. Kalache: None; L. Grenier: None; T. Cotton: None; O. Zahedi: None; M. Choi: AbbVie/Abbott, 2, 6, Amgen, 2, 6, AstraZeneca, 2, 6, Bristol-Myers Squibb(BMS), 2, 6, Celgene, 2, 6, Celltrion, 2, Eli Lilly, 2, 6, GlaxoSmithKlein(GSK), 2, Janssen, 2, 6, Mallinckrodt Pharmaceuticals, 2, Merck/MSD, 2, MitogenDx, 8, Organon, 2, Pfizer, 2, 6, Roche, 2, Werfen, 2.

To cite this abstract in AMA style:

Krustev E, Fritzler M, Bernatsky S, St-Pierre Y, Vinet E, Pineau C, Mendel A, Kalache F, Grenier L, Cotton T, Zahedi O, Choi M. Anti-Myxovirus Resistance Protein 1: A Novel Biomarker for Autoimmune Myositis and Interstitial Lung Disease in Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/anti-myxovirus-resistance-protein-1-a-novel-biomarker-for-autoimmune-myositis-and-interstitial-lung-disease-in-systemic-lupus-erythematosus/. Accessed .

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