Background/Purpose:

Systemic Sclerosis (SSc) is an autoimmune disease characterized by inflammation, fibrosis, and vasculopathy. Historical data indicates approximately 90% of patients with SSc test positive for anti-nuclear antibodies using immunofluorescence (IF-ANA) as well as for scleroderma specific extractable nuclear antibodies such as topoisomerase (Scl-70), centromere, THTO, U3RNP, U1RNP and RNA Polymerase III. However, a small subset of scleroderma patients test negative for anti-nuclear antibodies. The purpose of this study was to investigate whether scleroderma patients with negative IF-ANA had different characteristics when compared to scleroderma patients with positive IF-ANA.

Methods:

This study was IRB approved and all patients consented to be included in the study. At the time of data lock, 68 patients fulfilled diagnostic criteria for systemic sclerosis. Data was collected on patient demographics, autoantibody profile, clinical findings, internal organ involvement, modified Rodnan Skin Score (mRSS) and Medsger Severity Scale. IF-ANA testing was performed using the Hep-2 cell line through Laboratory Corporation of America (LabCorp, Burlington, NC).

Results:

Of the 68 patients, 54 had positive IF-ANA and 14 had negative IF-ANA. There was no significant difference in age, sex, race or scleroderma subtype (sine, limited, diffuse, or localized) between the IF-ANA positive and negative groups. There was no significant difference in mRSS at baseline between the IF-ANA positive and negative groups. However, patients in the IF-ANA negative group had a significantly lower mRSS at follow-up (p=0.02). This significant improvement was driven both by patients treated with immunosuppression and a small number of patients who were found to have underlying malignancy and whose scleroderma went into remission with treatment of the malignancy. Notably however, the IF-ANA negative group was also more likely to have positive U3RNP (p=0.009) indicating that this antibody may be missed using IF-ANA.

Conclusion:

Scleroderma patients with negative IF-ANA testing appeared to have milder progression of mRSS with therapy at follow-up indicating that this subgroup of patients may have a relatively better prognosis. Additionally, this study found that U3RNP antibody was more commonly seen in the IF-ANA negative subgroup indicating that this  antibody subtype may be missed using commercially available IF-ANA testing. This is an important finding since scleroderma patients with U3RNP are at higher risk for life threatening complications of scleroderma, including pulmonary hypertension and pulmonary fibrosis.