A cross-sectional study of autoantibody profiles in the Waikato systemic sclerosis cohort, New Zealand.

The autoantibody profiles in New Zealand systemic sclerosis patients have not previously been reported. The aim of this study was to evaluate the autoantibody profiles of patients in the Waikato Hospital Systemic Sclerosis Clinic cohort. The EUROLINE (IgG) Systemic Sclerosis panel test kit (which tests for Scl-70, CENP-A, CENP-B, RP11, RP155, Fib, NOR90, Th/To, PM100, PM75, Ku, PDGFR and Ro-52) was selected for the purpose of this study. All patients attending the Waikato Hospital Systemic Sclerosis clinic were invited to participate. These patients were categorised by systemic sclerosis subtypes [1]. Results were compared with previously published data, including the EUSTAR database. Sixty patients (56 female) were recruited, with a median age of 61 years (range 29-81 years). Forty-one had limited cutaneous systemic sclerosis (lcSSc). Of these lcSSc patients, 31 (75.6%) were positive for CENP-A and CENP-B (anti-centromere) antibodies, 12 (29.3%) for Ro-52 antibodies, 5 (12.2%) for RP11 and RP155, 4 (9.8%) for Scl-70 and 1 (2.4%) each for anti-Fib and Th/To antibodies. Fifteen patients had diffuse cutaneous systemic sclerosis (dcSSc), of which 7 patients (47.6%) were positive for RP11 and RP155, 4 (26.7%) for Scl-70. Three dcSSc patients did not have either of these two major antibodies, but of these 15 dcSSc patients, 4 patients (26.7%) were positive also for Ro-52, 2 (13.3%) for anti-Ku, and 1 (6.7%) each for anti-Fib and NOR90. Four patients had overlap syndrome (OLS), 1 had CENP-A and CENP-B antibodies, 1 had Ro-52 autoantibodies 1 had anti-Ku antibodies. Three patients had no autoantibodies. This is the first study to look at the autoantibody profile of SSc patients in New Zealand. A higher prevalence of antibodies against centromere and RNA polymerase III was demonstrated in our group compared with the EUSTAR database suggesting that antibody prevalence may vary geographically.

Serological profile of patients with systemic sclerosis.

INTRODUCTION: The systemic sclerosis-associated autoantibodies include anti-centromere, anti-topoisomerase I (anti-topo I), anti-RNA polymerase III, anti-fibrillarin, anti-Th/To, and anti-PDGFR. A specific serological profile is connected with clinical manifestations and prognosis in systemic sclerosis (SSc). OBJECTIVES: The aim of the study was to assess the serological profile in limited cutaneous and diffuse cutaneous SSc (lcSSc and dcSSc). PATIENTS AND METHODS: 87 (68 female and 19 male) consecutive SSc patients treated between 2006 and 2011 were assessed. Patients fulfilled the American College of Rheumatology classification criteria of SSc: 35 - dcSSc and 52 - lcSSc. The following marker antibodies were determined: anti-topo I, anti-centromere A and B (CENP A, CENP B), anti-RNA polymerase III (RP11, RP 155), anti-fibrillarin (U3RNP), anti- -NOR90, anti-Th/To, anti-PM-Scl-100, anti-PM-Scl-75, anti-Ku, anti-Ro-52, anti-PDGFR. The presence of antibodies was assessed using a test - EUROLINE Systemic Sclerosis Profile. RESULTS: 82 patients (94%) had positive antinuclear antibodies; anti-topo I - 29 patients; anti-CENP-A - 20 and anti-CENP-B - 20; anti-RP11 - 9 and anti-RP155 - 7; anti-U3RNP - 1; anti-NOR90 - 6; anti-Th/ To - 3; anti-PM-Scl-100 - 7; anti-PM-Scl-75 - 11; anti-Ku - 5; anti-Ro-52 - 23 patients. We found significant differences in prevalence of anti-topo I: 25/35 vs. 4/52 p=0.0000; anti-CENP A: 0/35 vs. 20/52 p=0.0001; anti-CENP B: 0/35 vs. 20/52 p=0.0001 between dcSSc and lcSSc. CONCLUSIONS: Some antibodies in SSc, e.g. anti-topo I and anti-centromere, are useful in defining the clinical subset of disease and provide prognostic information. There are no significant differences in the prevalence of other autoantibodies associated with SSc between dcSSc and lcSSc patients.

Antinuclear antibody profile in juvenile rheumatoid arthritis.

Immunoblot positive sera from children with juvenile rheumatoid arthritis detected from 1 to greater than or equal to 10 proteins in HeLa nuclear sonicates. Thirty percent of the sera reacted with histone H1. Antibodies to at least 1 of 6 most frequently detected nonhistone proteins were present in 85% of the sera. Using immunopurified antibodies to each of the 6 common antigens, we found that 4 of them were associated with mitotic chromosomes. Most sera detected at least 1 of these 4 nonhistone chromosomal proteins. Fifteen percent of the sera immunoprecipitated ribonucleoproteins; some exhibited a novel specificity, precipitating mature transcripts of RNA polymerase III. When present, antibodies to a 45 kDa protein occur only in sera from children without iritis and not in those with active iritis. Overall, the antibody profiles were highly individual and did not appear to correlate with disease subtype or activity.

The control of ribosomal RNA transcription in lymphocytes. Evidence that the rate of chain elongation is the limiting factor.

During activation of lymphocytes by phytohaemagglutinin, the nuclear activity of RNA polymerase I increases with no proportional increase in the amount of catalytic efficiency of the enzyme in the cell. The mechanism by which rRNA transcription in lymphocytes is modified by phytohaemagglutinin stimulation was investigated. The following results were obtained. (a) In resting lymphocytes all RNA polymerase II molecules are bound to the template while a pool of excess free RNA polymerase I, not engaged in transcription, can be detected by its ability to transcribe added poly[d(A-T)]. (b) Although the free RNA polymerase I activity increases twofold to threefold during phytohaemagglutinin stimulation, there is no evidence that the free enzymes ever become engaged in transcription. (c) Most of the RNA chains in elongation in nuclei from resting lymphocytes are being elongated by class II RNA polymerase and their rate of elongation is much higher than that of other RNA species. (d) The same number of pre-rRNA chains are in the process of being elongated in nuclei from resting and stimulated lymphocytes. However, the rate of elongation of pre-rRNA, which is slow relative to the average in resting lymphocytes, increases twofold to threefold within 6 h of phytohaemagglutinin stimulation and rises to sixfold by 19 h. These results suggest that the control of rRNA transcription in phytohaemagglutinin-stimulated lymphocytes lies in the elongation step of transcription rather than in initiation, and that little or no additional rRNA template is transcribed in phytohaemagglutinin-stimulated lymphocytes.