Background/Purpose:

Autoantibodies in scleroderma (systemic sclerosis, SSc) such as anti-topoisomerase I (Scl-70), RNA polymerase III, centromere, U3RNP/fibrillarin, and Th/To are associated with a unique subset of the disease and useful biomarkers in diagnosis and management. Among these, anti-Th/To is found in 4-13% of SSc patients and believed to be relatively specific for SSc, however, some reports show the detection of anti-Th/To in patients without SSc or some specific features such as interstitial lung disease (ILD). We sought to further characterize the clinical significance of anti-Th/To by focusing on non-SSc patients in an unselected cohort of rheumatology patients. 

Methods:

Patients enrolled in the registry from 2000 to 2012 were studied.  All sera collected at the initial visit of each patient were tested by immunoprecipitation of ³⁵S-methionine-labeled K562 cell extracts. In addition, 132 SSc and 45 non-SSc sera that had predominant nucleolar staining reported from diagnostic laboratories were tested by urea-PAGE and silver staining for RNA component analysis. Anti-Th/To was defined based on detection of 7-2 and 8-2 RNA in the immunoprecipitates. The clinical information of anti-Th/To positive patients were collected from the database and analyzed.

Results:

Overall, 16 patients were found to have anti-Th/To; 7 had sclerodermatous skin changes (SSc group) while 9 patients had neither sclerodermatous skin changes nor a diagnosis of SSc (non-SSc group). All except one in the non-SSc group were female and 7/7 SSc and 7/9 non-SSc were Caucasians (2 in non-SSc were African Americans). In the SSc group, 5 had limited cutaneous (lcSSc) disease and 2 had the diffuse cutaneous (dcSSc) variant. In the non-SSc group, there was 1 SLE with Sjogren’s (SjS), 1 with polymyositis (PM) and 2 with primary SjS. Other patients had a diagnosis based on organ involvement or symptoms, such as ILD, pulmonary hypertension (PH), and/or Raynaud’s phenomenon (RP). Most non-SSc group patients had features typically associated with SSc: 5/9 RP, 2/9 pitting scars, 3/9 telangiectasias, 3/9 ILD, 2/9 PH. No SSc patients had ILD or PH.  4/9 patients in the non-SSc group may be considered sine scleroderma; 2 with ILD and RP (one also with PH) and 1 with PH and telangiectasias. Another patient had SjS, Hashimoto’s thyroiditis and ILD complicated by diffuse alveolar hemorrhage that resulted in his death.

	Scleroderma (n = 7)	No scleroderma (n = 9)
Female, Caucasian	7/7, 7/7	8/9, 7/9
Age (mean)	48	48
Raynaud’s	86% (6/7)	56% (5/9)
Pitting scars	0% (0/7)	22% (2/9)
Telangiectasia	71% (5/7)	33% (3/9)
Interstitial Lung Disease	0% (0/7)	33% (3/9)
Pulmonary Hypertension	0% (0/7)	22% (2/9)
Esophageal Dysmotility	43% (3/7)	0% (0/9)
Pericardial effusion	14% (1/7)	22% (2/9)

Conclusion:

A significant number of patients with anti-Th/To did not have a diagnosis of SSc. However, most of these patients were found to have other features associated with SSc, many of which may be considered the sine scleroderma variant. In particular, non-SSc patients with anti-Th/To were found to be enriched for ILD and PH when compared to SSc patients with anti-Th/To. It may be worth testing for anti-Th/To in patients with ILD or PH and anti-nucleolar antibodies. Further studies on the clinical significance of anti-Th/To in non-SSc patients are warranted.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-features-associated-with-anti-thto-in-non-scleroderma-patients-sine-scleroderma/