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Anti-RNA polymerase III (RNAP III) antibodies are highly specific for scleroderma (SSc) and associated with diffuse SSc and renal crisis. Coexistence of anti-RNAP III and other SSc autoantibodies is rarely documented. We report three cases with coexisting anti-RNAP III and anti-U1RNP. Autoantibodies in 3829 sera from rheumatology clinics were screened by immunoprecipitation. Anti-RNAP III-positive sera were also examined by immunofluorescence and anti-RNAP III ELISA. In total, 35 anti-RNAP III-positive sera were identified by immunoprecipitation, in which three had coexisting anti-U1RNP. All three were anti-RNAP III ELISA positive. Two had anti-RNAP I dominant (vs. RNAP III) reactivity and showed strong nucleolar staining. A case with anti-U1/U2RNP (U2RNP dominant) had systemic lupus erythematosus (SLE)–SSc overlap syndrome; however, the remaining two cases had SLE without signs of SSc. All three cases of anti-RNAP III + U1RNP fulfilled ACR SLE criteria but none in the group with anti-RNAP III alone ( p = 0.0002). In contrast, only one case in the former group had sclerodermatous skin changes and Raynaud's phenomenon, vs. 92% with scleroderma in the latter ( p

The York Avenue (New York) ‘ecosystem’from the 1940s through the 1980s enabled Henry Kunkel to apply new scientific methodology to understandinghuman disease. Stephanie Smith, a young woman with lupus, was treated at the Rockefeller University Hospital in the 1960s. Studies of her antinuclear antibodies by Kunkel and Eng Tan led to the discovery of a precipitin line specific for lupus, and the responsible antigen was designated Sm (for ‘Smith’). This review outlines the history of Sm antigen from an interesting precipitin line to the identification of small nuclear RNA molecules and small nuclear ribonucleoproteins, and subsequently the discovery of RNA splicing. The story illustrates Henry Kunkel’s approach to science, emphasizing how ‘accidental’clinical observations, in the hands of skilled investigators, can have unexpectedand potentiallymomentous implications.

We report a woman with systemic lupus erythematosus (SLE) with diffuse proliferative glomerulonephritis and anti-dsDNA antibodies whose serum contained autoantibodies specific for the phosphorylated form of RNA polymerase II (RNAP IIO), Su and ribosomal P antigen, as well as anti-topoisomerase I antibodies, a marker for scleroderma (SSc). Over 6 years, the patient exhibited clinical manifestations consistent with SLE without clinical evidence of scleroderma. The reactivity of her serum autoantibodies with the phosphoproteins ribosomal P, topoisomerase I, and RNAP IIO is consistent with recognition of autoepitopes comprised in part of phosphate groups. This may explain the unexpected coexistence of marker autoantibodies for SLE and scleroderma, possibly with implications for the mechanisms of autoantibody generation.

Measurement of high sensitivity C-reactive protein (hs-CRP), has been used in the assessment of disease activity in numerous rheumatic conditions including systemic lupus erythematosus (SLE). However, the utility of hs-CRP measurement in patients with lupus is uncertain. This study examined if hs-CRP can be used to assess disease activity, severity and cardiovascular risk in SLE. Serum samples from 601 visits of 213 SLE patients and 134 controls were analysed for hs-CRP by nephelometry. Detailed demographic data were obtained from all subjects and medication history and key laboratory parameters were collected. Disease activity was assessed using the SLEDAI. High sensitivity CRP was not associated with disease activity (SLEDAI), number of ACR SLE criteria or presence of any particular organ involvement. hs-CRP levels were significantly correlated with standard cardiovascular risk factors including body weight ( P = 0.0002), hypertension ( P = 0.001), and apolipoprotein A-I ( P < 0.0001). Interestingly an inverse correlation was seen between hs-CRP levels and antimalarial use ( P = 0.0018). Our results suggest that measurement of hs-CRP, though not valuable as marker of disease activity in SLE may be of some use in the assessment of cardiovascular risk. We speculate that antimalarials may help to reduce cardiovascular risk in patients with SLE.

The frequent coexistence of anti-Ro and anti-La autoantibodies is well described, however, there is little evidence of sequential development of these two autoantibodies. We report a case of typical Sjogren's syndrome with high titer anti-Ro antibodies, who subsequently developed anti-La antibodies later in the course. This case suggests that the anti-La anti bodies may actually follow the anti-Ro antibodies in some cases as hypothesized in the concept of linked set of autoantibodies, analogous to development of anti-Sm in certain anti-nRNP antibody positive SLE patients and animal models.

Titers of anti-double-stranded (ds) DNA antibodies in sera from patients with systemic lupus erythematosus (SLE) using the Crithidia luciliae assay method were compared by conventional titration vs the titration emulation method (ImageTiter1) to evaluate whether the latter assay can replace manual titration. Titers by the two methods were identical or within one dilution in 98% (41=42) of samples. A single sample showed a two-dilution difference. Titration emulation showed a tendency to under-estimate the titer of high titer anti-dsDNA samples, although the difference was small. Titration emulation is a suitable alternative to the conventional titration method, offering an accurate and cost-effective approach to quantification of anti-dsDNA antibodies.