1658: Association Between Anti-Sjögren Syndrome/Scleroderma Autoantigen 1 (SSSCA1) Antibodies and Cancer in Systemic Sclerosis

Rachel Wallwork¹, Livia Casciola-Rosen¹ and Ami Shah², ¹Johns Hopkins University, Baltimore, MD, ²Johns Hopkins Rheumatology, Baltimore, MD

Background/Purpose: We sought to examine the association between anti-Sjögren syndrome/scleroderma autoantigen 1 (SSSCA1) antibody and cancer in systemic sclerosis (SSc). We also describe the frequency of anti-SSSCA1 antibody positivity and associated clinical phenotype in patients with SSc.

Methods: We conducted a case-control study using data from 210 patients with SSc and cancer, and 205 SSc patients without cancer. All were randomly selected from the Johns Hopkins Scleroderma Center Research Registry. Antibodies against SSSCA1 were assayed by immunoprecipitation of ³⁵S-methionine-labeled protein generated by in vitro transcription and translation. We performed logistic regression analysis to examine the relationship between anti-SSSCA1 antibodies and cancer.

Results: Among the 415 study patients, 31 (7%) were anti-SSSCA1-antibody positive. Patients with cancer were significantly more likely to be anti-SSSCA1 positive compared to those without cancer (22/210 [10%] vs. 9/205 [4%], respectively; p=0.018). After adjusting for age at SSc onset, sex, race, cutaneous subtype, follow up time and a history of smoking, patients with anti-SSSCA1 antibodies had an increased risk of cancer (OR 2.37, 95% CI 1.03, 5.46) compared to anti-SSSCA1-negative patients. Antibody-positive patients were more likely to have severe Raynaud's phenomenon, a lower minimum ejection fraction, a trend toward more severe heart involvement (defined by arrhythmia, left ventricular EF< 45% or clinical signs of heart failure), and a lower baseline DLCO percent predicted than anti-SSSCA1-negative patients.

Conclusion: These data suggest anti-SSSCA1 antibody status serves as a biomarker for cancer in patients with SSc. Anti-SSSCA1 positive patients with SSc may be more likely to have severe Raynaud's and cardiac involvement.


Categorical variables are presented as no. (%), continuous variables are presented as mean (SD) unless otherwise noted.
A p-value in bold indicates a statistically significant difference between anti-SSSCA1+ and anti-SSSCA1-

Unless otherwise stated, values represent whether the manifestation has ever emerged or maximal disease severity over the course of follow up.
Abbreviations: ACR: American College of Rheumatology; DLCO: diffusing capacity of the lungs for carbon monoxide; FVC= forced vital capacity; GI = gastrointestinal; IQR = interquartile range; mRSS = modified Rodnan skin score; no. = number; pred = predicted; RP=Raynaud’s phenomenon; SD = standard deviation; SSc = systemic sclerosis; sx: symptom

Explanations:
*Pulmonary hypertension defined by estimated right ventricular systolic pressure (RVSP) ≥45 mmHg on echocardiogram.

^ Moderate-severe disease: weight loss/anemia = weight loss ≥ 10.0 kg or hematocrit ≤ 32.9; Raynaud’s syndrome = digital pits, ulceration or gangrene; lung = FVC and/or DLCO < 70% predicted, mild-severe PH or oxygen dependence; heart = left ventricular ejection fraction < 45%, clinical signs of left or right heart failure or sustained clinically important arrhythmia; GI = high dose acid reflux medications, antibiotics for bacterial overgrowth, malabsorption syndrome, episodes of pseudo-obstruction or total parental nutrition requirement; kidney = serum creatinine ≥ 1.7 mg/dL, or at least 2+ urine protein; muscle = strength of ≤ 3/5 in upper or lower extremities, or requirement of ambulatory aids.

†SSc onset is defined as date of Raynaud’s phenomenon or non-Raynaud’s phenomenon symptom, whichever was first. Positive values denote cancer diagnosis after SSc onset, and negative values indicate cancer preceding SSc onset.
Disclosures: R. Wallwork, Intellia Therapeutics, EDITAS MEDICINE INC COM; L. Casciola-Rosen, None; A. Shah, Arena Pharmaceuticals, Medpace/Eicos, Kadmon Corporation.