Is anti-SRP (signal recognition particle) antibody associated with interstitial lung disease (ILD)?

Anti-SRP Antibody and Interstitial Lung Disease Association

Anti-SRP antibodies are associated with interstitial lung disease (ILD), though this is not the primary or most characteristic manifestation of anti-SRP myopathy. The predominant clinical phenotype is severe necrotizing myopathy with acute onset, markedly elevated creatine kinase, and cardiac involvement, but ILD does occur in a subset of patients 1, 2.

Primary Clinical Associations of Anti-SRP

Anti-SRP antibodies target a 6-polypeptide complex and are found in approximately 5-10% of adult patients with idiopathic inflammatory myopathies 1. The hallmark features include:

• Necrotizing myopathy with acute onset and severe proximal muscle weakness 1, 2
• Markedly elevated muscle enzymes (creatine kinase levels) 1, 2
• Dilated cardiomyopathy and cardiac disease 1, 2, 3
• Poor response to standard immunosuppression 1, 2

Evidence for ILD Association

Prevalence and Clinical Significance

ILD occurs in approximately 50% of anti-SRP positive patients in some cohorts, representing a significant extramuscular manifestation 4. A Chinese cohort study found that ILD was present in 50% of anti-SRP IIM patients and served as a predictor of poor prognosis (odds ratio 3.8,95% CI: 1.0-6.8, p = 0.05) 4.

Case Reports and Clinical Observations

• Anti-SRP associated ILD has been documented in both pediatric and adult populations 3
• Severe cases requiring lung transplantation have been reported, though these are rare 5
• ILD may present with massive pleural effusion in some cases 6
• The presence of ILD appears more common in certain ethnic populations, with higher incidences reported in Chinese cohorts 4

Important Clinical Distinctions

Anti-SRP is NOT among the primary myositis-specific antibodies strongly associated with ILD, unlike the antisynthetase antibodies (anti-Jo-1, PL-7, PL-12, etc.) which are the hallmark of antisynthetase syndrome with ILD as a cardinal feature 1, 7. The antisynthetase antibodies are found in 30-40% of IIM patients and characteristically present with fever, mechanic's hands, Raynaud phenomenon, myositis, ILD, and arthritis 1, 7.

Comparison with Other Antibodies

• Antisynthetase antibodies: ILD is a defining feature, present in the majority of cases 1, 7
• Anti-MDA5 antibodies: Associated with aggressive ILD, particularly in Asian populations 1
• Anti-Ro-52 antibodies: Strongly associated with ILD in connective tissue diseases (sensitivity 96.2%, specificity 83.3%) 2
• Anti-SRP antibodies: ILD occurs but is not the predominant manifestation 1, 2, 4

Clinical Implications

When evaluating a patient with anti-SRP antibodies:

• Screen for ILD with pulmonary function tests (spirometry and DLCO) and high-resolution CT chest, as ILD occurs in up to 50% of cases 4
• Recognize that ILD presence may indicate worse prognosis and require more aggressive immunosuppression 4
• Prioritize cardiac evaluation given the strong association with dilated cardiomyopathy 1, 2, 3
• Expect treatment resistance as anti-SRP myopathy typically responds poorly to standard immunosuppression 1, 2

Common Pitfall

Do not assume that the absence of severe myopathy excludes anti-SRP disease—rare cases present with severe ILD and only mildly elevated creatine kinase without overt necrotizing myopathy on biopsy 5. Unexplained worsening interstitial infiltrates with persistent hypoxic respiratory failure and nonspecifically elevated creatine kinase should prompt consideration of anti-SRP antibody testing 5.