Background/Purpose:

Antinuclear antibodies (ANA) in a nucleolar pattern (antinucleolar antibodies, ANoA) by indirect immunofluorescence technique correlate with several autoantibody specificities and clinical manifestations in scleroderma (systemic sclerosis, SSc). However, the full repertoire of this autoantibody diversity is not completely defined. In this study, we investigated the breadth of antibody specificities by radioimmunoprecipitation (IP) assay in a subset of SSc patients with ANoA but negative for three main disease markers [topoisomerase-I (topo-1/Scl-70), centromere (ACA) and RNA polymerase III (RNAP III)].

Methods:

In a cohort of 1000 patients with SSc, we identified 160 individuals with a positive ANoA and negative for ACA by immunofluorescence and topo-1 and RNAP III by ELISA. All 160-serum samples were further evaluated by IP using ³⁵S-methionine labeled K562 cell extract to identify specificities of ANoA in the sera.

Results:

Of the 160 patient specimens investigated, 152 (95%) had antibodies previously reported in SSc. No known antibodies were identified in 8 patients (5%). The repertoire of identifiable autoantibodies included scleroderma specific (U3-RNP, Th/To, PM/Scl, topo I, RNAP III) and non-specific (NOR90, U1-RNP, Su, and Ro60) autoantibodies. The distribution of the specific antibodies based on clinical manifestations and ethnicity is summarized in Table 1. The anti-U3RNP antibody was the most prevalent (49%; 78/160) and occurred predominantly in individuals of African American descent (68%; 53/78) with diffuse SSc (72%; 38/53). Although less prevalent in Caucasians and Hispanics, anti-U3-RNP also correlated with diffuse SSc in these groups. Of note, anti-Th/To autoantibodies were found mainly in limited SSc in Caucasians (85%; 22/26) and Hispanics (70%; 7/10). Anti-PM/Scl antibodies were primarily observed in Caucasians (70%; 16/23) and mostly in patients with limited (62%; 10/16) versus diffuse (38%; 6/16) disease.

Conclusion:

Among AnoA positive SSc patients, anti-U3RNP is the most common specificity (85%, 53/62) in African American and Hispanic (36%, 12/33) whereas anti-Th/To is the most prevalent in Caucasians (40%, 26/65). This study further highlights the relevance of autoantibody diversity and ethnicity in the stratification of SSc patients for management. 

Table 1. Scleroderma-specific Autoantibody profile based on race and clinical manifestations in antinucleolar antibody-positive patients