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Rosalind Ramsey-Goldman

Publications and source records attributed to Rosalind Ramsey-Goldman.

At least 19 recordsLinked to original sources
PubMed2026

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with systemic lupus erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within IRF7. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA-binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in interferon-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of the corresponding risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits.

ancient DNA↗
PubMed2026

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

UNLABELLED: Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with Systemic Lupus Erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within the IRF7 gene. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in IFN-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of a homologous risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent genetic IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits. HIGHLIGHTS: Genetic analysis using modern and evolutionary datasets identifies a persistent and highly prevalent lupus-associated coding haplotype in IRF7 at 11p15 The IRF7 lupus risk haplotype increases IFN-α production by monocytes and airway epithelial cells The IRF7 lupus risk haplotype increases IRF7 DNA binding strength and alters DNA sequence specificity A homologous lupus risk variant in mouse Irf7 enhances control of vesicular stomatitis virus and exacerbates autoantibody production.

Journal Article↗
PubMed2006

Duration of illness is an important variable for untreated children with juvenile dermatomyositis.

OBJECTIVE: To evaluate the impact of duration of untreated symptoms in children with juvenile dermatomyositis (JDM) on clinical and laboratory status at diagnosis. STUDY DESIGN: We examined physical and laboratory data from the first physician visit for 166 untreated children with JDM. Disease activity scores (DASs) assessed skin and muscle involvement. Height and weight were compared with the National Health and Nutrition Examination Survey III dataset. Duration of untreated illness was designated as the time from first sign of rash or weakness to diagnostic visit. RESULTS: Boys and girls with untreated JDM were shorter and lighter than national norms (P > .0005 for both), and nonwhite children were weaker than white children (P > .0005). Older children had more dysphagia (P = .017) and arthritis (P > .001). Duration of untreated JDM was negatively associated with DAS weakness (P > .0005), unrelated to DAS skin, and positively associated with pathological calcifications (P = .006). With untreated disease > or = 4.7 months, serum levels of 4 muscle enzymes (aldolase, lactic dehydrogenase, creatine kinase, serum glutamic-oxaloacetic transaminase/aspartate aminotransferase) tended toward normal (P > .01 for each). CONCLUSIONS: Duration of untreated symptoms is an important variable and should be included in decisions concerning both diagnostic criteria and intensity of therapy for children with JDM.

Abdominal Pain↗
PubMed2006

Lymphoma in a patient with systemic lupus erythematosus.

BACKGROUND: A 40-year-old woman with a 10-year history of systemic lupus erythematosus (SLE) presented with fever, lymphadenopathy and fatigue. Before that time, her SLE symptoms had been controlled with hydroxychloroquine, NSAIDs, and an occasional short course of moderate-dose prednisone. Two months before presentation, she experienced fevers ranging from 38.3 to 39.7 degrees C, but she had no specific symptoms that suggested local infection. INVESTIGATIONS: Physical examination, multiple blood cultures, and laboratory investigations that included the following tests: hemoglobin concentration; erythrocyte sedimentation rate; C-reactive protein level; serum lactate dehydrogenase level; aspartate aminotransferase level; alanine aminotransferase level; serum complement C3 and C4 levels; white-blood-cell count; platelet count; urinalysis; serum creatinine level; CT of the chest and abdomen; bone-marrow biopsy; serum electrophoresis; and tests for Epstein-Barr virus, cytomegalovirus, hepatitis B virus, hepatitis C virus, HIV-1, antinuclear antibodies, antibodies to Smith antigen, antibodies to double-stranded DNA, and antibodies to Ro and La. DIAGNOSIS: Stage IVB diffuse large B-cell lymphoma with marrow and liver involvement concurrent with SLE. MANAGEMENT: The patient promptly underwent chemotherapy, receiving three courses of 3 mg/m(2) vindesine on day 1, 1,500 mg/m(2) cyclophosphamide and 80 mg/m(2) doxorubicin on day 2, and 50 mg/m(2) prednisolone on days 1-5.

Adult↗
PubMed2006

Malignancy and autoimmunity.

PURPOSE OF REVIEW: The association of cancer with autoimmune disease has been under investigation for several years. Reports have appeared suggesting increased cancer risk in autoimmune rheumatic diseases. Evidence has been accumulating recently in rheumatoid arthritis, Sjogren's syndrome, systemic lupus erythematosus, and scleroderma/systemic sclerosis. This review focuses on recent publications regarding risk of cancer in these conditions. RECENT FINDINGS: Despite a lack of a strong association between rheumatoid arthritis and cancer overall, studies show an increased risk for the development of lymphoma in rheumatoid arthritis. There are data suggesting an increased risk for rheumatoid arthritis patients regarding lung cancer. In Sjogren's syndrome-related malignancies, most publications in the past year relate to non-Hodgkin's lymphomas, and suggest possible mechanisms driving the association. Data substantiate an increased risk of certain cancers in systemic lupus erythematosus; the risk appears to be most heightened for lymphoma. A recent cohort study examined cancer risk in scleroderma; the estimates were lower than previous studies had suggested, and the confidence intervals relatively imprecise, making a definitive conclusion difficult. SUMMARY: There have been several papers published related to cancer in the rheumatic diseases, particularly inflammatory arthritis, Sjogren's syndrome, systemic lupus erythematosus, and scleroderma/systemic sclerosis. Continuing interest in the association between autoimmune rheumatic diseases and malignancy is likely, given the potential impact in terms of understanding both rheumatic diseases and cancer.

Autoimmune Diseases↗
PubMed2006

Time to renal disease and end-stage renal disease in PROFILE: a multiethnic lupus cohort.

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE). METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic-demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE. In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcgammaRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model. CONCLUSIONS: Fcgamma receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated.

Adult↗
PubMed2005

Cancer screening in patients with systemic lupus erythematosus.

OBJECTIVE: To examine whether patients with systemic lupus erythematosus (SLE) undergo cancer screening according to established guidelines, to compare their reported screening practices with information from the general population, and to examine potential predictors of screening within our SLE sample. METHODS: We conducted a patient survey of cancer screening practices within the Montreal General Hospital lupus cohort. We compared self-reported frequency of cancer screening to guidelines suggested for the general population, and to figures for cancer screening reported in the general population. We also developed logistic regression models to establish potential predictors of screening for patients with SLE, with cervical cancer screening being the outcome of interest in our primary analyses. RESULTS: Of 48 women aged 50-69, 53% (95% confidence interval, CI: 38-68) had had a mammogram in the past 12 months, compared to 74% (95% CI: 73-75) for similarly aged Quebec women. Of 51 subjects aged 50 and older, only 18% (95% CI: 8-34) reported screening (fecal occult blood check with or without endoscopy) within the recommended time frame, compared to 48% (95% CI: 45-51) for colorectal screening for persons > 50 in the general population. Only 9 of 27 patients with SLE aged less than 30 had Pap tests in the past 12 months (33%, 95% CI: 19-52), compared with a general population rate of 56% (95% CI: 53-59) for similarly aged Quebec women. Our logistic regression model suggested that, among the SLE patients, non-whites, those with lower education, and those with higher disease damage scores were less likely to undergo cervical Pap testing. CONCLUSION: These data suggest that appropriate cancer screening may be overlooked in patients with SLE.

Adult↗
PubMed2005

Premature atherosclerotic disease in systemic lupus erythematosus--role of inflammatory mechanisms.

Mounting evidence from a growing body of epidemiologic studies demonstrates that patients with systemic lupus erythematosus (SLE) are at increased risk for the development of premature cardiovascular disease (CVD). However, awareness of accelerated atherosclerosis in young SLE patients, albeit growing, is still limited, as documented by the brief case presented. Inflammation is thought to play an important role in both the pathogenesis of SLE, as well as atherosclerotic vascular disease. Inflammatory processes that are shared by SLE and atherosclerotic disease include immune complex deposition and fixation, autoantibody binding, complement activation and CD40-CD40 ligand interaction. By examining the inflammatory mechanisms in common between SLE and atherosclerotic disease, we can come to a better understanding of the pathophysiology of the accelerated atherosclerotic process seen in patients with SLE and can gain insights into developing and instituting preventative and treatment strategies. In this article, we present a case of a young woman with SLE who presents with chest pain, followed by a review of inflammation-based pathogenic mechanisms that are shared by SLE and atherosclerotic cardiovascular disease.

Adult↗
PubMed2005

History of infection before the onset of juvenile dermatomyositis: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry.

OBJECTIVE: To obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM). METHODS: Parents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis. RESULTS: Children for which both a parent interview and physician medical records at diagnosis were available (n = 286) were included. Diagnoses were as follows: definite/probable JDM (n = 234, 82%), possible JDM (n = 43, 15%), or rash only (n = 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were < or =4 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics. CONCLUSION: This study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.

Causality↗
PubMed2005

Revisiting the issue of malignancy risk in systemic lupus erythematosus.

Certain cancers occur more frequently in systemic lupus erythematosus (SLE) as compared with the general population, as recent data substantiates. The risk appears to be most heightened for lymphoma. Several pathogenic mechanisms may explain these observations, although little is definitively known. One particular concern relates to whether cancer risk in SLE is increased by medication exposures. Cooperative efforts to evaluate this have been undertaken by the Systemic Lupus International Collaborating Clinics and the Canadian Network for Improved Outcomes in Systemic Lupus research groups. This and other works in progress will, it is hoped, considerably advance the knowledge regarding the association between autoimmune diseases and malignancy.

Comorbidity↗
PubMed2005

Bone health and systemic lupus erythematosus.

Osteoporosis is a potentially preventable condition frequently encountered in patients with systemic lupus erythematosus (SLE). Bone loss in SLE is likely a multi- factorial process involving traditional osteoporosis risk factors along with lupus-related factors. Recognizing potential contributors to bone loss in patients with SLE may allow earlier detection of osteoporosis, optimize bone health, and minimize future fracture risk. This paper discusses recent epidemiologic information related to osteoporosis and fractures in SLE, and highlights relevant developments regarding evaluation and treatment of patients at risk for bone loss.

Bone Density↗
PubMed2005

Exploring the links between systemic lupus erythematosus and cancer.

For decades, concern has been mounting that individuals with systemic lupus erythematosus (SLE) have increased susceptibility to cancer. Recent data confirm that certain cancers, particularly hematologic, occur more frequently in SLE than in the general population. Numerous pathogenic mechanisms are possible, but hypotheses remain largely speculative. In particular, data are inadequate on how cancer risk in SLE may be related to medication exposures. To evaluate the impact of medication exposures on cancer risk in SLE, cooperative efforts of Systemic Lupus International Collaborating Clinics and Canadian Network for Improved Outcomes in Systemic Lupus are currently in progress. This should provide much-needed insight into the pathogenesis of the association between cancer and SLE.

Humans↗
PubMed2005

Osteoporosis in systemic lupus erythematosus mechanisms.

Osteoporosis is a potentially preventable condition frequently encountered in patients who have systemic lupus erythematosus (SLE). Bone loss in SLE is heterogeneous and likely a multifactorial process involving both traditional and lupus-related risk factors. Recognizing potential contributors to bone loss in the SLE patient may allow for earlier detection of osteoporosis and optimize bone health. This article reviews the current epidemiologic information available on osteoporosis and fracture data in SLE and discusses evaluation and management strategies pertinent to patients who have lupus.

Humans↗
PubMed2005

An osteoporosis and fracture intervention program increases the diagnosis and treatment for osteoporosis for patients with minimal trauma fractures.

BACKGROUND: As fewer than 25% of patients with an osteoporotic minimal trauma fracture (MTF) are evaluated and treated for osteoporosis, an osteoporosis and fracture intervention program (OFIP) was developed. METHODS: Patients hospitalized with MTF were educated about and treated for osteoporosis and were evaluated by the osteoporosis team at 6 and 12 months after discharge. Patients seen in the emergency department were given information about osteoporosis and encouraged to seek medical care at the osteoporosis office. RESULTS: While 165 patients hospitalized with an MTF participated in the OFIP, 38 patients received routine osteoporosis education. At the 6-month follow-up, in the OFIP group, 68% of patients with hip fracture and 54% of patients with non-hip fracture were taking antiresorptive medications. There was no change in treatment rate among patients receiving conventional care. CONCLUSIONS: The rates of diagnosis of osteoporosis and treatment implementation following an MTF increased when the intervention occurred at the time of hospitalization.

Academic Medical Centers↗
PubMed2004

Effects of prasterone on disease activity and symptoms in women with active systemic lupus erythematosus.

OBJECTIVE: To determine whether prasterone administration results in improvement or stabilization of systemic lupus erythematosus (SLE) disease activity and its symptoms. METHODS: Women with active SLE were treated with prasterone 200 mg/day plus standard SLE treatments or with placebo plus standard SLE treatments for up to 12 months in this randomized, double-blind investigation conducted at 27 centers. Standard SLE treatments included prednisone (</=10 mg/day), antimalarials, and immunosuppressive agents; dosages were required to be stable for >/=6 weeks prior to enrollment and remain unchanged during protocol treatment. Responders were patients who experienced no clinical deterioration and had improvement or stabilization over the duration of the study in 2 disease activity measures (the SLE Disease Activity Index [SLEDAI] and the Systemic Lupus Activity Measure) and 2 quality of life measures (patient's global assessment and the Krupp Fatigue Severity Scale). RESULTS: A total of 381 women with SLE were enrolled. Among patients with clinically active disease at baseline (SLEDAI score >2), 86 of 147 in the prasterone group (58.5%) demonstrated improvement or stabilization without clinical deterioration, as compared with 65 of 146 in the placebo group (44.5%) (P = 0.017). Acne and hirsutism were reported in 33% and 16%, respectively, of the prasterone group and in 14% and 2%, respectively, of the placebo group (P < 0.05 for both comparisons). However, most cases of acne and hirsutism were mild and did not require withdrawal from therapy. Myalgias and oral stomatitis were reported less frequently in the prasterone group (22% and 15%, respectively) than in the placebo group (36% and 23%, respectively) (P < 0.05 for both comparisons). Serum levels of high-density lipoprotein cholesterol, triglycerides, and C3 complement significantly decreased, while levels of testosterone and, to a lesser extent, estradiol increased in the prasterone group. CONCLUSION: In adult women with active SLE, administration of prasterone at a dosage of 200 mg/day improved or stabilized signs and symptoms of disease and was generally well tolerated.

Adjuvants, Immunologic↗
PubMed2003

US incidence of juvenile dermatomyositis, 1995-1998: results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Registry.

OBJECTIVE: To estimate the incidence of juvenile dermatomyositis (juvenile DM) in the United States between 1995 and 1998. METHODS: Physician referrals to the National Institute of Arthritis and Musculoskeletal and Skin Diseases Juvenile Dermatomyositis Research Registry and the National Pediatric Rheumatology Disease Registry from Indiana University were utilized for a 2-source capture-recapture estimation of Juvenile DM annual incidence. RESULTS: For children 2-17 years of age, the estimated annual incidence rates from 1995 to 1998 in the US ranged from 2.5 to 4.1 juvenile DM cases per million children, and the 4-year average annual rate was 3.2 per million children (95% confidence interval 2.9-3.4). Estimated annual incidence rates by race were 3.4 for white non-Hispanics, 3.3 for African American non-Hispanics, and 2.7 for Hispanics. During the 4-year period of the study, completeness of ascertainment for the combined registries ranged from 56% to 86% and girls were affected more than boys (ratio 2.3:1). CONCLUSION: This study provides evidence for sex, and possibly racial differences in the risk of juvenile DM in the US.

Adolescent↗