# The Relationship Between Immune Semaphorins and Myasthenia Gravis

**Authors:** Dilcan Kotan, Esen Çiçekli, Özlem Aydemir

PMC · DOI: 10.1002/brb3.71291 · Brain and Behavior · 2026-02-27

## TL;DR

This study explores how immune semaphorins, specifically 4A and 7A, differ in patients with myasthenia gravis compared to healthy individuals, suggesting their potential as diagnostic and therapeutic targets.

## Contribution

The study identifies altered levels of semaphorins 4A and 7A in myasthenia gravis patients, offering new insights into immune regulation in the disease.

## Key findings

- Semaphorin 4A levels were significantly lower in MG patients compared to controls.
- Semaphorin 7A levels were significantly higher in MG patients compared to controls.
- No significant correlation was found between semaphorin levels and disease stage.

## Abstract

Myasthenia gravis (MG) is an autoimmune disease involving several immune mechanisms. Recently, semaphorins have emerged as potential diagnostic and prognostic biomarkers in autoimmune neurological and non‐neurological diseases. This study investigated the role of immune semaphorins, namely semaphorins 3A, 3F, 4A, 4D, and 7A, in the diagnosis and prognosis of MG and their potential as biomarkers.

Serum levels of semaphorin 3A, 3F, 4A, 4D, and 7A were compared between 41 patients with MG and 39 healthy controls. Patients were grouped according to the Myasthenia Gravis Activities of Daily Living scale, and differences in semaphorin levels between groups were analyzed.

Semaphorin 4A levels were significantly lower, whereas semaphorin 7A levels were higher in patients with MG than in controls. However, no significant correlation was found between the disease stage and semaphorin levels.

Our findings suggest that the levels of semaphorin 4A and 7A may not only support the diagnosis of MG and aid in differential diagnosis but also shed light on the development of future therapeutic protocols targeting semaphorin proteins and receptors in other autoimmune and inflammatory diseases.

Serum alterations of immune‐related semaphorins in myasthenia gravis. Patients exhibited decreased semaphorin 4A and increased semaphorin 7A levels compared with healthy controls. These changes highlight disturbed immune regulation in myasthenia gravis and support the involvement of semaphorin‐mediated pathways in autoimmune neuromuscular junction disorders.

## Linked entities

- **Proteins:** SEMA3A (semaphorin 3A), SEMA3F (semaphorin 3F)
- **Diseases:** myasthenia gravis (MONDO:0009688)

## Full-text entities

- **Genes:** NRP1 (neuropilin 1) [NCBI Gene 8829] {aka BDCA4, CD304, NP1, NRP, VEGF165R}, Sema4d (sema domain, immunoglobulin domain (Ig), transmembrane domain (TM) and short cytoplasmic domain, (semaphorin) 4D) [NCBI Gene 20354] {aka CD100, Semacl2, Semaj, Semcl2, coll-4}, AGRN (agrin) [NCBI Gene 375790] {aka AGRIN, CMS8, CMSPPD}, NRP2 (neuropilin 2) [NCBI Gene 8828] {aka NP2, NPN2, PRO2714, VEGF165R2}, SEMA7A (semaphorin 7A (JohnMiltonHagen blood group)) [NCBI Gene 8482] {aka CD108, CDw108, H-SEMA-K1, H-Sema-L, JMH, PFIC11}, MUSK (muscle associated receptor tyrosine kinase) [NCBI Gene 4593] {aka CMS9, FADS}, SEMA4A (semaphorin 4A) [NCBI Gene 64218] {aka CORD10, RP35, SEMAB, SEMB}, SEMA3F (semaphorin 3F) [NCBI Gene 6405] {aka SEMA-IV, SEMA4, SEMAK}, SEMA3A (semaphorin 3A) [NCBI Gene 10371] {aka COLL1, HH16, Hsema-I, Hsema-III, SEMA1, SEMAD}, LRP4 (LDL receptor related protein 4) [NCBI Gene 4038] {aka CLSS, CMS17, LRP-4, LRP10, MEGF7, SOST2}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}
- **Diseases:** CNS (MESH:D002493), neuroinflammation (MESH:D000090862), Huntington's (MESH:D006816), cerebral ischemia (MESH:D002545), cancers (MESH:D009369), Alzheimer's disease (MESH:D000544), peripheral nerve injury (MESH:D059348), autoimmune neurological and non-neurological diseases (MESH:D020274), diseases (MESH:D004194), autoimmune, demyelinating, and neurodegenerative diseases (MESH:D019636), Myasthenia (MESH:D020294), vasculitis (MESH:D014657), sarcopenia (MESH:D055948), muscle damage (MESH:D009133), autoimmune and inflammation- (MESH:D007249), Myasthenia Graves (MESH:D006111), coronary artery stenosis (MESH:D023921), spinal cord injuries (MESH:D013119), NMJ disorder (MESH:D020511), nematode (MESH:D009349), thymic hyperplasia (MESH:D013952), autoimmune activity (MESH:D001327), hypoxic (MESH:D002534), rheumatologic diseases (MESH:D012216), immune (MESH:D007154), cerebral infarction (MESH:D002544), infection (MESH:D007239), cardiovascular diseases (MESH:D002318), rheumatoid arthritis (MESH:D001172), ALS (MESH:D000690), MG (MESH:D009157), Lambert-Eaton myasthenic syndrome (MESH:D015624), NM disease (MESH:D009468), multiple sclerosis (MESH:D009103), Kawasaki disease (MESH:D009080), muscle injury (MESH:D009135), thymoma (MESH:D013945), EAE (MESH:D004681), axonal degeneration (MESH:D009410), musculoskeletal disorders (MESH:D009140)
- **Chemicals:** steroid (MESH:D013256)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

37 references — full list in the complete paper: https://tomesphere.com/paper/PMC12949199/full.md

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Source: https://tomesphere.com/paper/PMC12949199