Antimicrobial Peptide LL-37 May Trigger Autoimmune Muscle Disease Through Interferon Activation

The antimicrobial peptide LL-37 was elevated in muscle tissue of patients with polymyositis (PM) and dermatomyositis (DM) compared to healthy controls, primarily released by infiltrating neutrophils. Plasmacytoid dendritic cells (BDCA-2+, the main type I interferon producers) and the interferon marker MxA were also elevated in affected muscle. All PM/DM patients with short disease duration had low vitamin D levels. The findings support the hypothesis that LL-37 may trigger the type I interferon system in these autoimmune muscle diseases, similar to its known role in lupus (SLE).

Case-control study comparing tissue biopsies from PM and DM patients with SLE patients and healthy controls. Muscle and skin biopsies were immunohistochemically stained for LL-37, neutrophils (CD66b), plasmacytoid dendritic cells (BDCA-2), MxA (interferon marker), and macrophages (CD68, CD163). Double staining confirmed LL-37 expression in neutrophils. Serum vitamin D (25(OH)D3) levels measured in 8 myositis patients and 40 healthy controls.

LL-37 is normally a protective antimicrobial peptide, but this study reveals its darker side: in autoimmune diseases, it may trigger harmful immune responses. The finding that LL-37 activates the same interferon pathway in myositis as it does in lupus suggests a common peptide-driven mechanism across multiple autoimmune diseases. The vitamin D connection is also notable, since vitamin D regulates LL-37 expression.

LL-37's role in autoimmunity is a double-edged sword story: the same peptide that protects against infections can, under certain conditions, trigger harmful immune responses. Its involvement has already been established in lupus and psoriasis. This study extends the pattern to autoimmune myositis, suggesting LL-37 may be a common pathogenic factor across multiple autoimmune diseases. The vitamin D connection raises the intriguing possibility that vitamin D deficiency could worsen autoimmunity by dysregulating LL-37.

Very small sample sizes (3-5 patients per group) limit statistical power and generalizability. Cross-sectional design cannot establish whether LL-37 elevation is a cause or consequence of the inflammatory process. The study cannot prove that LL-37 triggers myositis — only that it's present at higher levels and correlates with interferon markers.