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Background <p>Anti-survival of motor neuron (SMN) antibodies have recently been identified in rheumatic and musculoskeletal diseases (RMDs), notably mixed connective tissue disease (MCTD). However, their immunological characteristics, prevalence, and clinical relevance beyond MCTD remain poorly understood. This study aimed to elucidate the clinical significance of anti-SMN antibodies in a wide spectrum of RMDs.</p> Methods <p>We assessed anti-SMN antibodies and antibody-producing cells using Western blotting and immunofluorescence staining with recombinant SMN complexes. Serum anti-SMN antibody titers were measured using a recombinant SMN complex-bound magnetic bead assay in 906 serum samples from patients with 16 types of RMDs and healthy controls. Clinical associations and treatment responses were analyzed.</p> Results <p>Western blotting using patients’ sera confirmed SMN-specific antibodies. Immunofluorescence staining identified anti-SMN antibody-producing plasma cells in an MCTD patient’s lymph node. Anti-SMN antibodies were detected in 36.7% of MCTD, 10.6% of systemic lupus erythematosus (SLE), and 2.4% of systemic sclerosis patients, while none of the healthy controls were positive. Antibody titers were higher against the SMN complex than individual components, highlighting the importance of the complex structure. In MCTD, antibody positivity was strongly correlated with interstitial lung disease (90.9% vs. 36.8%, <i>P</i> = .013). In SLE, antibody-positive patients had significantly lower white blood cell counts and complement levels, higher anti-ds-DNA antibody titer, and higher prevalence of serositis (35.0% vs. 11.3%), gastrointestinal involvement (15.0% vs. 2.4%), nephritis (70.0% vs. 30.4%), and higher median SLE Disease Activity Index scores (19.5 vs. 5.0) compared to antibody-negative patients (all <i>P</i> &lt; .05). Antibody titers decreased after treatment (− 71.5% at 3 months, <i>P</i> = .010) and increased upon relapse.</p> Conclusions <p>Anti-SMN antibodies are prevalent in MCTD and SLE. Consistent with prior studies, their titers in MCTD were associated with distinct clinical features. Importantly, we newly demonstrate that in SLE, anti-SMN antibody levels correlate with immune complex–related manifestations and disease activity, providing a novel and clinically significant insight. These findings highlight their potential as biomarkers for disease stratification, organ involvement, and monitoring disease progression in RMDs.</p>

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Anti-survival of motor neuron antibodies in rheumatic and musculoskeletal diseases: prevalence, clinical associations, and biomarker potential, with novel insights into disease activity in SLE

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月2日

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  • Yuki Imai,
  • Masaru Takeshita,
  • Koji Suzuki,
  • Hiroyuki Fukui,
  • Kazunori Furuhashi,
  • Kotaro Matsumoto,
  • Jun Kikuchi,
  • Keiko Yoshimoto,
  • Yuko Kaneko

摘要

Background

Anti-survival of motor neuron (SMN) antibodies have recently been identified in rheumatic and musculoskeletal diseases (RMDs), notably mixed connective tissue disease (MCTD). However, their immunological characteristics, prevalence, and clinical relevance beyond MCTD remain poorly understood. This study aimed to elucidate the clinical significance of anti-SMN antibodies in a wide spectrum of RMDs.

Methods

We assessed anti-SMN antibodies and antibody-producing cells using Western blotting and immunofluorescence staining with recombinant SMN complexes. Serum anti-SMN antibody titers were measured using a recombinant SMN complex-bound magnetic bead assay in 906 serum samples from patients with 16 types of RMDs and healthy controls. Clinical associations and treatment responses were analyzed.

Results

Western blotting using patients’ sera confirmed SMN-specific antibodies. Immunofluorescence staining identified anti-SMN antibody-producing plasma cells in an MCTD patient’s lymph node. Anti-SMN antibodies were detected in 36.7% of MCTD, 10.6% of systemic lupus erythematosus (SLE), and 2.4% of systemic sclerosis patients, while none of the healthy controls were positive. Antibody titers were higher against the SMN complex than individual components, highlighting the importance of the complex structure. In MCTD, antibody positivity was strongly correlated with interstitial lung disease (90.9% vs. 36.8%, P = .013). In SLE, antibody-positive patients had significantly lower white blood cell counts and complement levels, higher anti-ds-DNA antibody titer, and higher prevalence of serositis (35.0% vs. 11.3%), gastrointestinal involvement (15.0% vs. 2.4%), nephritis (70.0% vs. 30.4%), and higher median SLE Disease Activity Index scores (19.5 vs. 5.0) compared to antibody-negative patients (all P < .05). Antibody titers decreased after treatment (− 71.5% at 3 months, P = .010) and increased upon relapse.

Conclusions

Anti-SMN antibodies are prevalent in MCTD and SLE. Consistent with prior studies, their titers in MCTD were associated with distinct clinical features. Importantly, we newly demonstrate that in SLE, anti-SMN antibody levels correlate with immune complex–related manifestations and disease activity, providing a novel and clinically significant insight. These findings highlight their potential as biomarkers for disease stratification, organ involvement, and monitoring disease progression in RMDs.