To gain insight into the mechanisms of autoantibody induction, sera from 40 patients with systemic lupus erythematosus (SLE) were tested by ELISAs for antibody binding to denatured individual histones, native histone-histone complexes, histone-DNA subnucleosome complexes, three forms of chromatin, and DNA. Whole chromatin was the most reactive substrate, with 88% of the patients positive. By chi-square analysis, only the presence of anti-(H2A-H2B), anti-[(H2A-H2B) -DNA], and antichromatin were correlated with kidney disease measured by proteinuria > 0.5 g/d. SLE patients could be divided into two groups based on their antibody-binding pattern to the above substrates. Antibodies from about half of the patients reacted with chromatin and the (H2A-H2B) -DNA subnucleosome complex but displayed very low or no reactivity with native DNA or the (H3-H4)2-DNA subnucleosome complex. An additional third of the patients had antibody reactivity to chromatin, as well as to both subnucleosome structures and DNA. Strikingly, all sera that bound to any of the components of chromatin also bound to whole chromatin, and adsorption with chromatin removed 85-100% of reactivity to (H2A-H2B)-DNA, (H3-H4)2-DNA, and native DNA. Individual sera often bound to several different epitopes on chromatin, with some epitopes requiring quaternary protein-DNA interactions. These results are consistent with chromatin being a potent immunogenic stimulus in SLE. Taken together with previous studies, we suggest that antibody activity to the (H2A-H2B) -DNA component signals the initial breakdown of immune tolerance whereas responses to (H3-H4)2-DNA and native DNA reflect subsequent global loss of tolerance to chromatin. (J. Clin. Invest. 1994. 94:184-192.)
Controlled trial of medical treatment of active chronic otitis media Active chronic otitis media is a common condition affecting 0 6%,' of adults in the United Kingdom. Initial management is usually by general practitioners, who annually prescribe systemic and topical antibiotics on at least 178 000 and 73 000 occasions respectively (unpublished observations). Despite this there have been few studies of the efficacy of antibiotics,'-4 and no study has included a control group of untreated patients or of patients treated solely by aural toilet. We undertook a controlled study comparing appropriate systemic or topical antibiotic treatment with weekly aural toilet and insufflation of boric acid and iodine powder.
We studied the reliability and validity of the Chinese Short-Form 36 Health Survey (SF-36) in a cross sectional study of patients with systemic lupus erythematosus (SLE). Sixty-nine consecutive subjects completed a questionnaire containing the Chinese SF-36 twice within 14 d. Disease activity and damage were assessed using the British Isles Lupus Activity Group (BILAG) and SLICC/ACR Damage Index (DI) scales, respectively. Internal consistency was assessed using Cronbach's alpha, reliability using Spearman's correlation and repeatability coefficients, and relationships between SF-36, BILAG and DI scores using Spearman's correlation. The Chinese SF-36 showed high internal consistency (alpha = 0.72-0.91) and good reliability, with correlations exceeding 0.70 for 7 scales and mean scale score differences of < 2 points for 6 scales. SF-36 scores correlated weakly with BILAG scores (-0.27 to -0.41) and DI scores (-0.24 to -0.35), and subjects' mean SF-36 scores were 6-24 points lower than the general population, supporting construct validity of the SP-36. These data suggest that the Chinese SF-36 is a reliable and valid measure of quality of life in patients with SLE.
HLA-B27 is strongly associated with ankylosing spondylitis (AS) but the role of the HLA molecule itself is still unclear. In this study on Singapore Chinese, we have subtyped 50 B27 positive AS patients and 45 B27 positive normals and found that the B*2706 allele has a significant negative association with disease (p = 0.047). Together with recent data indicating the existence of AS "protective" B27 alleles, our data shows that the HLA molecule itself plays a crucial role in disease development.
We reviewed the case records of 10 Oriental patients with systemic lupus erythematosus (SLE) who developed pulmonary haemorrhage (PH) between 1987 and 1996 to determine their clinical presentation and outcome. All the patients had clinical evidence of PH including a sudden onset of dyspnoea, tachycardia, fall in haemoglobin (at least 1.5 gm%) and bilateral diffuse alveolar infiltrates on chest radiographs. At the time of PH, nine patients had a disease duration of 2 years or less and all the patients had clinical and/or laboratory evidence of active lupus disease. Fever and lung crepitations were present in 90% of patients while haemoptysis and chest pain occurred in only three and two patients, respectively. All the patients were treated with high dose intravenous corticosteroids and in addition seven had a combination of pulse methylprednisolone and cyclophosphamide, and four had received plasmapheresis. Four patients died as a result of PH. One patient died of pneumonia three years after recovering from PH while the remaining five had no recurrence of PH after a median follow-up of 22 months. Our study suggests that PH in Oriental lupus patients often occurs early in the disease, rarely presents with haemoptysis and has a high mortality despite aggressive immunosuppressive therapy.
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