1. Anti NXP2 myositis - A
review
RITASMAN BAISYA

2. Introduction
NXP-2 (anti-MJ) antibody targeting NXP2( nuclear matrix protein )
A myositis-specific antibody ( MSA )
Common in juvenile dermatomyositis patients, found in adults also
Association with calcinosis and malignancy
Severe muscle weakness and edema are important feature
Potential for gastrointestinal involvement

3. /
Aouizerate, J. et al. Muscle ischaemia associated with NXP2 autoantibodies: a severe subtype of juvenile
dermatomyositis. Rheumatology

4. Results
MSAs ( anti-NXP2 (9/23), anti-TIF1g (4/23), anti-MDA5 (2/23)) and no MSAs
(8/23) yielded two histopathological clusters.
Compared with cluster 2, patients in cluster 1 had-
1. Strikingly more often antiNXP2 antibodies (7/11 in cluster 1 vs 2/12 in cluster2 ),
2. More pronounced muscle weakness,
3. More gastrointestinal involvement
4. Required more aggressive treatment

5. Cluster 1 – more NXP2 positive patients , more severe disease
Cluster 1 (n = 11) with more NXP2 positivity showed a more severe and ischaemic pattern than
cluster 2 (n = 12) assessed by:
1. Total score severity > 20 (100.0% vs 25.0%);
2. Visual analogic score >6 (100.0% vs 25.0%);
3. The vascular domain score >1 (100.0% vs 41.7%);
4. Microinfarcts (100% vs 58.3%);
5. Ischaemic myofibrillary loss (focal punched-out vacuoles) (90.9 vs 25%) ,
6. Obvious capillary loss (81.8% vs 16.7)

6. Cluster 1 with more NXP2 positive
patients had more severe muscle
disease

7. D- CMAS (P = 0.003) and E- the % of patients in remission over a 1-year follow-up (P = 0.043). Dark blue
shading represents the NXP2+ group (9/23).
NXP2-positive subjects were more likely to present severe muscle involvement (MMT, P = 0.014; CMAS, P =
0.003) and required more treatment lines (P = 0.028)

8. Albayda J, Pinal-Fernandez I, Huang W, et al. Antinuclear Matrix Protein 2 Autoantibodies and Edema,
Muscle Disease, and Malignancy Risk in Dermatomyositis Patients. Arthritis Care Res (Hoboken).
2017;69(11):1771-1776. doi:10.1002/acr.23188

9. Results
In anti NXP2 group -
More severe muscle weakness .
More distal arm weakness (35% vs. 20%, p=0.02) & distal leg weakness
More neck weakness (48% vs. 23%, p<0.001)
More likely to present with myalgias (46% vs. 25%, p=0.002) and
develop dysphagia
No evidence for more diaphragmatic weakness
tMRIs showed increased muscle atrophy

10. Extramuscular features
Subcutaneous edema - 36% of patients with anti-NXP2 & 19% of anti-NXP-2-negative
patients
Calcinosis was more common in adult patients with anti-NXP-2 autoantibodies (30% vs
17%, p=0.02)
Patients with anti-NXP2 were found to have a 3.68-fold increased risk of cancer (95%CI
1.2-8.6).

11. Tansley et al , Juvenile Dermatomyositis Research Group. Calcinosis in juvenile dermatomyositis is influenced
by both anti-NXP2 autoantibody status and age at disease onset. Rheumatology (Oxford). 2014
Dec;53(12):2204-8.

12. Results
Anti-NXP2 autoantibodiess substantially increased the risk of calcinosis across all
ages (P = 0.025)
They were detectable prior to calcinosis development
Children with anti-NXP2 autoantibodies had a greater degree of weakness (median
lowest CMAS ever 29.6 vs 42)
They were less likely to be in remission at 2 years post-diagnosis.

13. Demographic data in NXP2 patients

14. • Anti-NXP2 seemed to be the most common antibody (30.6%) in the cohort
• Anti-NXP2 antibody-positive JDM of Chinese children was characterized by rash and
severe muscle weakness.
• Calcification high in NXP2 group .
• ILD in anti NXP2 is mild

15. Take home points
1. Anti-NXP2 autoantibodies ( originally called anti-MJ )were first reported in JDM cohort
2. They target NXP2 (MORC3), a protein involved in transcriptional regulation
3. First regarded as more specifically associated with calcinosis in JDM
4. They are also detected in adults & associated with malignancy
5. Muscle pain, subcutaneous edema, dysphagia, and both proximal and distal muscle
weakness
6. can be considered as complementary biomarkers associated with clinical severity and
poor prognosis