Session Information
Date: Monday, November 9, 2015
Title: Systemic Sclerosis, Fibrosing Syndromes and Raynaud's - Clinical Aspects and Therapeutics Poster II
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Systemic Sclerosis (SSc), Polymyositis (PM) and Dermatomyositis (DM) are characterized by the presence of serum autoantibodies (autoAbs) which are central in the diagnosis, predicting organ involvement, follow-up and therapy. However, patients can be negative for commercially available autoantibody tests such as anti-centromere (ACA), -topo I and RNA polymerase III in SSc and -Jo-1 in PM. Our aim is to apply immunoprecipitation (IP) to SSc and PM/DM patients to identify new and rare autoantibodies, to study their clinical association.
Methods: We investigated sera from consecutive patients with SSc (n=28, out of a total of 98 SSc patients attending our Unit in 2014-2015), PM (n=15) and DM (n=9) by protein-IP of 35S-methionine-labeled K562 cell extract followed by SDS-PAGE and autoradiography. Statistical analysis was performed by Prism (GraphPad Software 4.0) by Fisher exact test and statistical significance at p< 0.05.
Results: 28 SSc sera were tested by IP to identify rare autoAbs (see Table). A common set of several proteins of 140/40-25kD that needs further characterization for antigen identification was observed in 8 SSc cases. It is significantly associated with ACA positivity (50%, 8/16 ACA vs 0/12 others; p=0.008), and these patients have severe Raynaud’s with digital ulcers requiring IV prostacyclin (75%, 6/8 vs 7/54 ACA+, 13%; p=0.0006), with esophageal involvement in 4 cases. In 15 PM patients, one each of anti-TIF1 gamma/alpha, -PL-7 and -PL-12 were identified by IP. In 9 DM cases, IP identified 2 anti-Ro/SSA, 2 anti-Mi-2 and 1 anti-TIF1 gamma/alpha: this case had juvenile DM with Hodgkin’s lymphoma 3 years before the onset of DM symptoms.
|
Autoantibody |
Disease |
Sex |
ANA |
Disease manifestations |
Cancer |
|
Anti-Ku (n=1) |
Limited SSc |
Female |
Speckled |
Digital ulcers |
No |
|
Anti-replication protein A (n=1) |
Diffuse SSc |
Female |
ACA+ speckled |
Alveolitis, GI tract disease, fasciitis and digital ulcers |
No |
|
Anti-NOR90 (n=1) |
Limited SSc |
Male |
Speckled+ nucleolar |
Pulmonary fibrosis and pulmonary arterial hypertension |
Yes |
|
Anti-Ago2/Su (n=1) with anti-topo I |
Diffuse SSc |
Female |
Homogeneous+ nucleolar |
Alveolitis and digital ulcers |
No |
|
Anti-140/40-25k (n=8) |
Limited SSc |
Female |
ACA |
Digital ulcers (n=6), esophageal involvement (n=4) |
No |
|
Anti-TIF1 gamma/alpha (n=2) |
DM (n=1) PM (n=1) |
Female Male
|
Speckled |
High CPK at onset, no organ involved in both cases |
Yes in DM |
|
Anti-Mi-2 (n=2) |
DM |
Female |
Speckled |
Skin and muscle disease, no organ involvement |
Yes in 1 case |
|
Anti-PL-7 (n=1) |
PM |
Female |
Cytoplasmic |
Anti-synthetase syndrome |
No |
|
Anti-PL-12 (n=1) |
PM |
Female |
Nucleolar |
Anti-synthetase syndrome |
No |
Conclusion: Protein and RNA-IP can be used to identify rare and unknown autoantibodies in systemic autoimmune rheumatic diseases such as SSc and PM/DM and may identify new biomarkers for rare diseases.
To cite this abstract in AMA style:
Ceribelli A, Isailovic N, De Santis M, Generali E, Massarotti M, Satoh M, Selmi C. Identification and Clinical Correlations of Rare Autoantibodies in Systemic Sclerosis and Poly/Dermatomyositis Patients [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/identification-and-clinical-correlations-of-rare-autoantibodies-in-systemic-sclerosis-and-polydermatomyositis-patients/. Accessed .« Back to 2015 ACR/ARHP Annual Meeting
ACR Meeting Abstracts - https://acrabstracts.org/abstract/identification-and-clinical-correlations-of-rare-autoantibodies-in-systemic-sclerosis-and-polydermatomyositis-patients/