MRL/1 and BXSB male mice have a systemic lupus erythematosus (SLE)-like disease similar to but more acute than that occurring in NZB X W mice. The common elements of lymphoid hyperplasia, B-cell hyperactivity, autoantibodies, circulating immune complex (IC), complement consumption, IC glomerulonephritis with gp70 deposition, and thymic atrophy were found in all three kinds of SLE mice. On the basis of these common elements, SLE seen in these mice can be considered a single disease in the same sense that human SLE is one disease. The differences in the SLE expressed in the different mice are no greater than those found in an unselected series of humans with SLE. However, the significant quantitative and qualitative variations in abnormal immunologic expression suggest that different constellations of factors, genetic and/or pathophysiologic, may operate in the three murine strains and that each constellation is capable of leading, via its particular abnormal immunologic consequences, to the activation of common immunopathologic effector mechanisms that cause quite similar SLE-like syndromes. From an experimental point of view, the availability of several inbred murine strains of commonplace histocompatibility types that express an SLE-like syndrome makes possible innumerable manipulations which should help to elucidate the nature and cause(s) of this disorder.

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Abstract. We have detected and begun to characterize a 17-kD centromere-specific protein, CENP-A (Earnshaw, W. C., and N. Rothfield, 1985, Chromosoma., 91:313-321). Sera from several humans with CREST scleroderma autoimmune disease (CREST: calcinosis, Raynaud's phenomenon, esophageal dsymotility, sclerodactyly, and telangiectasia) bind this protein in immunoblot assays of HeLa whole cell or nuclear extracts. We have affinity purified the anti-17-kD centromere protein (anti-CENP-A) specific antibodies from immunoblots of HeLa nuclear protein. The antibodies react with epitopes present on CENP-A derived from humans but apparently do not recognize specific epitopes in either rat or chicken nuclei. Only human nuclear protein is CENP-A positive by immunoblot. Furthermore, human cells show localization of anti-CENP-A antibody to centromeres by immunofluorescence microscopy, whereas rat cells do not. On extraction from the nucleus, CENP-A copurifies with core histones and with nucleosome core particles. We conclude that this centromerespecific protein is a historic-like component of chromatin. The data suggest that CENP-A functions as a centromere-specific core histone.

A baseline skin score > or =20 was associated with heart involvement at baseline and predicted mortality and SRC over the subsequent 4 years. Improvement in skin score in these patients with diffuse cutaneous scleroderma was associated with improvement in hand function, inflammatory indices, joint contractures, arthritis signs, overall functional ability, and the examining investigator's global assessment of improvement.

The course of the skin score and the frequencies of SRC and mortality in the high-dose D-Pen group were not different from those in the low-dose D-Pen group. Eighty percent of the adverse event-related withdrawals occurred in the high-dose D-Pen patients. Although this study cannot answer the question of whether low-dose D-Pen is effective, it does suggest that there is no advantage to using D-Pen in doses higher than 125 every other day.

Objective. The reported frequency of scleroderma M01-R renal crisis (SRC) in diffuse systemic sclerosis (SSc; scleroderma) is 15-20%. Early use of angiotensinconverting enzyme (ACE) inhibitors has markedly improved outcome. The present analysis reexamines the prognostic factors for and outcome of SRC in a prospective cohort of patients with early diffuse SSc.Methods. We retrospectively evaluated the cohort of SSc patients who participated in the High-Dose Versus Low-Dose D-Penicillamine in Early Diffuse SSc trial. Patients with diffuse cutaneous scleroderma were enrolled if their disease duration was <18 months. Because the trial failed to show a difference between treatment groups, the data were pooled.Results. One hundred thirty-four SSc patients entered the observation period a mean ؎ SD of 0.8 ؎ 0.3 years after onset of SSc. SRC occurred in 18 patients a mean ؎ SD of 0.9 ؎ 1.1 years after entry. During a mean ؎ SD 4.0 ؎ 1.1 years of followup after entry, 9 of the 18 patients died (mean ؎ SD 0.6 ؎ 0.9 years after SRC onset). Baseline characteristics that predicted SRC included a modified Rodnan skin thickness score of >20 (P < 0.01), enlarged cardiac silhouette on radiograph (P ‫؍‬ 0.04), large joint contractures (wrist, elbow, knee) (P ‫؍‬ 0.008), and prednisone use at entry (P ‫؍‬ 0.01). Baseline characteristics that did not predict SRC included age, sex, race, Health Assessment Questionnaire score, fist closure, handspread, lung involvement, muscle weakness, erythrocyte sedimentation rate, and platelet count. In 5 of 10 subjects for whom at least 2 sequential skin scores were available, skin scores increased significantly (P ‫؍‬ 0.012) in the 6 months before onset of SRC.Conclusion. SRC occurred in 13% of patients soon (mean 11 months) after entry into the cohort.

Objective. To evaluate functional impairment in systemic sclerosis (SSc) patients with diffuse cutaneous scleroderma at the time of entry into a trial of a therapeutic intervention (D-penicillamine).Methods. The 20-item Disability Index of the Health Assessment Questionnaire (HAQ-DI) was administered to 134 patients as they entered a multicenter trial of high-dose versus low-dose D-penicillamine. All patients had diffuse SSc of <18 months' duration. SSc patients who had severe organ system involvement and recent renal crisis and who were receiving prednisone >10 mg/day were excluded from entry. Logistic regression modeling was used to examine the relationship of HAQ-DI scores to SSc skin and organ system involvement. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to estimate effects. Conclusion. Increased HAQ-DI scores at baseline were correlated with reduced fist closure, reduced handspread, elevated platelet count, presence of tender joints, older age, and female sex. The most important contributor to functional impairment was hand dysfunction. Even within the first 18 months after SSc onset, moderate-severe functional impairment (HAQ-DI scores >1.0) was frequent (53%) in this group of diffuse SSc patients. In early diffuse SSc, the self-administered HAQ-DI is therefore a valuable assessment of function that correlates with objective physical and laboratory

Two recently described murine strains, MRL/1 and BXSB, develop a lupus-like syndrome resulting in a 50% mortality by the fifth month of age. Comparison of the immunopathological and virological characteristics of these mice with those of the NZB/NZW F1 mouse reveals several pathogenetic common denominators but no obvious common etiologic factors. In all three kinds of mice, the lupus-like syndrome consists of a fatal immune complex type glomerulonephritis and complete or near complete thymic cortical atrophy plus lymphoid hyperplasia that varies in degree among the three kinds of mice. The nephritic glomeruli contain a concentration of antinuclear antibodies plus varying amounts of stainable gp70. This syndrome is consistently correlated with abnormally elevated serum IgG levels, antinuclear antibodies, anti ds- and ssDNA antibodies, and circulating immune complexes, as well as depressed serum hemolytic complement. Features that differ among the three kinds of mice include: H2 type, anti-lymphocyte antibody, cryoglobulins, T-B cell ratios, sex incidence of disease, vasculitis, and oncornaviral flora. The serum gp70 levels in the three mice also differ considerably, but all are within the range of gp70 levels found in some immunologically normal strains.