Autoantibodies in Juvenile Systemic Sclerosis

Katharine Moore^1,2, J. Lee Nelson^3,4, Marvin J. Fritzler⁵, Marisa S. Klein-Gitelman⁶, Ann M. Reed⁷, Tzielan C. Lee⁸ and Anne M. Stevens^1,9, ¹Pediatrics, University of Washington, Seattle, WA, ²Pediatric Rheumatology, Seattle Children's Hospital, Seattle, WA, ³University of Washington, Seattle, WA, ⁴Fred Hutchinson Cancer Research Center, Seattle, WA, ⁵Mitogen Advanced Diagnostics Laboratory, Faculty of Medicine, University of Calgary, Calgary, AB, Canada, ⁶Division of Rheumatology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL, ⁷Rheumatology, Mayo Clinic, Rochester, MN, ⁸Pediatric Rheumatology, Stanford University School of Medicine, Stanford, CA, ⁹Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, WA

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Antibodies, Pediatric rheumatology, pediatrics and systemic sclerosis

Session Information

Title: Pediatric Rheumatology - Pathogenesis and Genetics

Session Type: Abstract Submissions (ACR)

Background/Purpose: There are no known biomarkers for organ involvement, response to therapy, or prognosis in juvenile systemic sclerosis (jSSc). In adults with systemic sclerosis, a number of serum autoantibodies have been described, many of which have been associated with clinical phenotypes. Knowing the pattern of organ involvement associated with a particular autoantibody can be of benefit, with implications for both treatment and screening. The objective of this study was to determine the frequency and clinical significance of an extended panel of both scleroderma-specific and scleroderma-associated autoantibodies in patients with jSSc.

Methods: Stored plasma samples from 28 pediatric patients with systemic sclerosis, 26 with localized scleroderma and 35 age-matched healthy controls were tested for antinuclear antibodies (ANA) as well as antibodies against Ro52, platelet-derived growth factor receptor, Ku, PMScl-75, PMScl-100, Th/To, hUF/NOR-90, fibrillarin, RP155, RP11, centromere proteins A/B (CENP-A, CENP-B), and topoisomerase I/Scl-70 RNA. The majority of the stored samples were obtained after the initiation of treatment. Line immunoassay was used, with the exception of Th/To, which were assessed for by chemiluminescence.

Results: Of the 28 patients with jSSc, the most common antibodies detected were anti-PMScl-100 (17.9%), anti-Scl-70 (14.3%), anti-CENPB (10.7%) and anti-CENPA (7.1%). Anti-PMScl-75 and anti-RP155 were found in one patient each. By comparison, no autoantibodies were detected in the plasma from either healthy pediatric controls or juvenile localized scleroderma patients, except for ANA in five (17.9%) of the localized scleroderma samples and one control. Of the patients with jSSc, 15 (53.6%) were ANA positive but negative for both anti-Centromere (CENP-A /B) and Ant-Scl70. Of these, three carried antibodies to PMScl-100. There were no significant differences in antibody profile between limited and diffuse systemic disease, or with specific clinical disease manifestations.

Conclusion: In this cohort, the presence of autoantibodies targeting PMscl-100, Scl-70, and CENPA/B were highly specific for systemic sclerosis compared to localized scleroderma or controls. Testing for PMscl-100 helped capture additional patients who were ANA positive but anti-Centromere/anti-Scl70 negative, but there remained jSSc patients with ANA of unknown antigen specificity. Furthermore, the association of autoantibodies with systemic but not with localized scleroderma reinforces the concept of two distinct disease processes.

Disclosure:

K. Moore,
None;

J. L. Nelson,
None;

M. J. Fritzler,

Inova Diagnostics, Inc., San Diego, CA,

M. S. Klein-Gitelman,
None;

A. M. Reed,
None;

T. C. Lee,
None;

A. M. Stevens,
None.

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