Autoantibodies Recognizing Cytosolic 5’-Nucleotidase 1A Are Associated with More Severe Disease in Patients with Juvenile Myositis

Richard Yeker¹, Iago Pinal-Fernandez², Takayuki Kishi³, Ira N. Targoff⁴, Frederick W Miller³, Lisa G Rider³ and Andrew Mammen⁵, ¹National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, ²NIAMS, NIH, Bethesda, MD, ³Environmental Autoimmunity Group, National Institute of Environmental Health Sciences, National Institutes of Health, Bethesda, MD, ⁴VA Medical Center, University of Oklahoma Health Sciences Center, Oklahoma Medical Research Foundation, Oklahoma City, OK, ⁵Muscle Diseases Unit, National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health, Bethesda, MD

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: autoantibodies, autoimmune diseases, juvenile dermatomyositis, juvenile idiopathic arthritis (JIA) and juvenile myositis

Session Information

Date: Tuesday, November 7, 2017

Title: Muscle Biology, Myositis and Myopathies Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose: Autoantibodies recognizing cytosolic 5’-nucleotidase 1A (NT5C1A) are present in the sera of adults with myositis and other autoimmune diseases. They are especially prevalent in adults with inclusion body myositis (IBM), where they are associated with more severe weakness. This study was undertaken to define the prevalence and clinical features associated with anti-NT5C1A autoantibodies in juvenile myositis.

Methods: We screened sera from 380 juvenile myositis patients, 30 patients with juvenile idiopathic arthritis (JIA), and 92 healthy control children for anti-NT5C1A. Clinical characteristics were compared between myositis patients with and without anti-NT5C1A.

Results: Anti-NT5C1A autoantibodies were present in the sera of 102 of 380 (27%) patients with juvenile myositis, 11 of 92 (12%) healthy control children (p=0.002) and 27% of children with JIA (p=0.05 vs. controls). Eighty-three of 307 (27%) juvenile dermatomyositis and 16 of 46 (35%) juvenile overlap myositis patients’ sera were anti-NT5C1A positive (p<0.01 vs. controls for each). Only 3 of 27 (11%) juvenile polymyositis patients were anti-NT5C1A positive. Juvenile myositis patients with and without anti-NT5C1A autoantibodies had similar phenotypes. However, anti-NT5C1A positive myositis patients had more frequent hospitalizations (p=0.007), required more medications (p<0.001), and had higher early total, skin and lung symptom scores (p≤0.05) (Table 1). The HLA alleles DRB1*07 (21% vs. 9%, p=0.04) and DQA1*0201 (22% vs. 6%, p=0.005) were more frequent in anti-NT5C1A negative patients.

Conclusion: Anti-NT5C1A autoantibodies are present in 27% of children with myositis, as is the case for JIA. As in adults with IBM, juvenile myositis patients with anti-NT5C1A autoantibodies have more severe disease.

Table 1. Disease outcomes and medications received per anti-NT5C1A status.


	NT5C1A + (n=102)	NT5C1A – (n=278)	multivariate p-value

Disease Course
Monocyclic course	16% (12/76)	23% (53/229)	0.2
Polycyclic course	18% (14/76)	24% (56/229)	0.3
Chronic continuous course	66% (50/76)	52% (120/229)	0.07
Steinbrocker functional class at final assessment
Functional class 1	64% (65/102)	72% (198/274)	0.06
Functional class 2	29% (30/102)	18% (50/274)	0.01
Functional class 3	2% (2/102)	4% (11/274)	0.3
Functional class 4	5% (5/102)	5% (15/274)	0.9
Muscle enzymes
Peak creatine kinase	1010 (296-3971)	672 (252-5460)	0.6
Peak aldolase	16.9 (23.9)	20.8 (37.2)	0.9
Severity at onset	2.1 (1.4)	2.2 (0.9)	0.3
Early total symptom score	0.27 (0.12)	0.23 (0.11)	0.02
Early muscle score	0.38 (0.19)	0.38 (0.20)	0.6
Early joint score	0.52 (0.41)	0.43 (0.42)	0.1
Early skin score	0.29 (0.15)	0.24 (0.13)	0.05
Early gastrointestinal score	0.09 (0.13)	0.07 (0.10)	0.09
Early lung score	0.13 (0.17)	0.08 (0.15)	0.003
Early cardiac score	0.03 (0.08)	0.03 (0.08)	0.9
Early constitutional symptoms score	0.41 (0.26)	0.39 (0.27)	0.4
Mortality	4% (4/102)	3% (9/278)	0.6
Hospitalized	65% (62/96)	55% (148/268)	0.1
Number of hospitalizations	1.6 (2.3)	1.1 (1.7)	0.007
Need for wheelchair	21% (21/100)	18% (47/268)	0.07
Response to treatment
Complete clinical response	22% (19/87)	33% (74/225)	0.1
Remission	15% (13/88)	27% (63/232)	0.2
Total number of medications used	4.8 (2.0)	3.6 (2.0)	< 0.001
Treatment trials per year	3.0 (2.7)	2.1 (2.7)	0.10
Medications received
Oral steroids	99% (87/88)	99% (230/232)	0.8
Intravenous pulsed steroids	78% (69/88)	47% (110/232)	< 0.001
Methotrexate	83% (73/88)	71% (164/232)	0.03
Intravenous immunoglobulin	67% (59/88)	24% (55/232)	< 0.001
Other DMARDs	33% (29/88)	20% (46/232)	0.01

Dichotomous variables were represented as percentage (count/total), continuous variables as mean (SD) and the creatine kinase was presented as median (Q1-Q3). Multivariate analysis used linear or logistic regression adjusted for time of follow-up, autoantibodies and clinical groups. Creatine kinase was log-transformed prior to statistical analysis.

Disclosure: R. Yeker, None; I. Pinal-Fernandez, None; T. Kishi, The Myositis Association, 2; I. N. Targoff, Oklahoma Medical Research Foundation Clinical Immunology Laboratory, 6; F. W. Miller, None; L. G. Rider, None; A. Mammen, None.

To cite this abstract in AMA style:

Yeker R, Pinal-Fernandez I, Kishi T, Targoff IN, Miller FW, Rider LG, Mammen A. Autoantibodies Recognizing Cytosolic 5’-Nucleotidase 1A Are Associated with More Severe Disease in Patients with Juvenile Myositis [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/autoantibodies-recognizing-cytosolic-5-nucleotidase-1a-are-associated-with-more-severe-disease-in-patients-with-juvenile-myositis/. Accessed .

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