the role of antibodies in the diagnosis and risk-stratification of different types of inflammatory myopathies, focusing on Myositis-Specific Antibodies (MSA).

1. ROLE OF ANTIBODIES
IN MUSCLE DISEASES
MOHAMED E. ABD-ELHADY, MSC
APRIL 2023

2. MUSCLE’S
ANATOMY

6. (I) IDIOPATHIC INFLAMMATORY MYOPATHIES

8. INFLAMMATORY MYOPATHIES
• Dermatomyositis, Polymyositis, and Inclusion Body Myositis (IBM)
• Immune Mediated Necrotizing Myopathy (IMNM): AB against HMG-CoA
reductases.
• Systemic Autoimmune Rheumatic Diseases (SARD)
• Overlap Syndrome and ADM/CADM
• The main concern is their association with tumors and/or auto-autoimmune
disorders, which guides the investigations and management.

11. ANTIBODIES IN INFLAMMATORY MYOPATHIES
• Myositis-Specific Antibodies (MSA) and Myositis-Associated Antibodies (MAA).
• MSA: is defined as autoantibody specificities that are considered relatively specific for
PM/DM.
• MAA: autoantibody specificity found in PM/DM but not specific for this diagnosis and
may be found in other SARD

12. • Role of AB in inflammatory myopathies:
I) For associated autoimmune disease (MAA): ESR, RF, ANA, ANCA C & P, anti-
Ds-DNA, anti phospholipid AB, anti-PM-Scl, anti-Ku, anti-
U1ribonucleoprotein (RNP) U1/U2RNP, anti-Ro 60 and anti-La.
II) For associated malignancies: Tumor Markers

13. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-ARS (aminoacyl tRNA synthetases):
autoantibodies that recognize the cytoplasmic amino acid-charging enzymes,
aminoacyl tRNA synthetases. Eight of them including histidyl (Jo-1), threonyl (PL-7),
alanyl (PL-12), glycyl (EJ), isoleucyl (OJ), asparaginyl (KS), phenylalanyl (ZO), and
tyrosyl (YRS/HA) tRNA synthetases have been reported.
They can be further classified into either anti-Jo-1 or anti-non-Jo-1 Abs.
Anti-Jo-1 (anti-synthetase syndrome) is the 1st identified MSA and is associated
with ILD, polyarteritis, and Raynaud’s phenomenon.
Anti-Jo-1 antibodies, usually found in 15–25 % of PM/DM patients, are by far the
most common among anti-ARS antibodies; all others are usually found only in 0.5–
6 % of patients

14. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-ARS (aminoacyl tRNA synthetases):
anti-PL-7/PL-12 was associated with early and severe ILD and less myositis (CADM).
In summary, patients with any anti-ARS have a similar clinical syndrome known as
anti- synthetase syndrome; however, several recent studies suggest that antibodies
to non-Jo-1 ARS are associated with earlier and more severe ILD and poor
prognosis compared with anti-Jo-1 (+) patients. Also, non-Jo-1 anti-ARS (+)
patients are more likely to have ILD without typical myositis.

15. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-SRP (anti-signal recognition particle):
anti-SRP is associated with classic PM and some were unusually severe and/or rapid
onset, with low prevalence of ILD or Raynaud’s phenomenon.
The most common Ab in patients with necrotizing myopathy.
anti-SRP is specific for PM and associated with treatment-resistant severe myopathy,
which is histologically characterized by necrotizing myopathy

16. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-Mi-2
Anti-Mi-2 was associated with classic DM (classic features of DM including Gottron’s
papules, heliotrope rash, shawl sign, and V-sign), but a risk to develop clinically
significant ILD is low and cancer is uncommon, good response to steroids, and
good prognosis.

17. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-MDA5/CADM140 (anti-melanoma differentiation-associated gene 5):
A subset of DM patients may have typical DM skin rash but have little or no muscle
involvement (Amyopathic DM).
Anti-CADM 140: A subset of CADM may develop rapidly progressive interstitial lung
disease, resistant to treatment and with poor prognosis.

18. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-TIF1γ/α and β (Antibodies to transcription intermediary factor 1γ/α):
TIF1α, TIF1β, and TIF1γ belong to the TIF family of transcription cofactors
It has a striking association with cancer-associated DM (42–100 %).
Almost all anti-TIF1γ/α positive patients have DM with typical skin rash but a low
prevalence of ILD.

19. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-MJ/NXP-2
nuclear matrix protein. NXP-2 localizes in the promyelocytic leukemia (PML) nuclear
bodies, where it recruits and activates p53 to induce cellular senescence.
Anti-MJ/NXP-2-positive patients showed typical DM skin rash with a higher
prevalence of ILD, and was specifically associated with cancer in males.
Absent in PM.

20. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-SAE (small ubiquitin-like modifier-activating enzyme)
SAE-1: small ubiquitin-like modifier-activating enzyme A subunit
SAE-2: SUMO-1(small ubiquitin-like modifier-1) activating enzyme B subunit
Found in DM but not PM.
In patients with anti-SAE, a high frequency of cutaneous lesions including
heliotrope and Gottron rash were identified, patients with anti-SAE, a high
frequency of cutaneous lesions including heliotrope (82 %) and Gottron rash (82 %)
were identified

21. MYOSITIS-SPECIFIC ANTIBODIES
• Anti-Cn1A (antibody against cytosolic 5’nucleotidase 1A):
In IBM

28. (II) MUSCULAR DYSTROPHIES

30. • Addition of these new antibodies to clinical practice in the future will help in
making earlier and more accurate diagnoses and better management for patients.

31. IS IT APPLICABLE?

34. REFERENCES
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