High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis.

Objective: Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the effect of IFN in LN.

Methods: Two hundred and twenty-one patients with systemic lupus erythematosus were studied.

Baseline characteristics and long-term outcomes of eosinophilic fasciitis in 89 patients seen at a single center over 20 years.

Aim: Eosinophilic fasciitis (EF) is a rare, fibrosing disorder of skin and subcutaneous tissue. This study was undertaken to describe its clinical and laboratory features and identify prognostic factors associated with outcome.

Methods: We conducted a retrospective review of all EF patients evaluated at our institution from 1 January1997 to 30 December 2016.

Gastrointestinal and Extra-Intestinal Manifestations of IgG4-Related Disease.

IgG4-related disease (IgG4-RD) is a chronic relapsing multi-organ fibro-inflammatory syndrome of presumed autoimmune etiology. It is characterized by increased serum levels of IgG4 and tissue infiltration by IgG4 cells. Increased titers of autoantibodies against a spectrum of self-antigens and response to steroids have led to its characterization as an autoimmune disease.

Broad Concepts in Management of Systemic Lupus Erythematosus.

Systemic lupus erythematosus is a multisystem autoimmune disease with protean manifestation. Although commonly seen in young women, it can affect men as well as elderly patients. Approach to treatment is multidisciplinary, involves defining the extent of organ involvement, and distinguishing between active manifestations and damage.

Concomitant Disruption of and Genes Facilitates the Development of Double Negative αβ TCR Peripheral T Cells That Respond Robustly to Staphylococcal Superantigen.

Mature peripheral double negative T (DNT) cells expressing αβ TCR but lacking CD4/CD8 coreceptors play protective as well as pathogenic roles. To better understand their development and functioning in vivo, we concomitantly inactivated and genes in mice with intact MHC class I and class II molecules with the hypothesis that this would enable the development of DNT cells. We also envisaged that these DNT cells could be activated by bacterial superantigens in vivo as activation of T cells by superantigens does not require CD4 and CD8 coreceptors.

Risk of Cerebrovascular Accidents and Ischemic Heart Disease in Cutaneous Lupus Erythematosus: A Population-Based Cohort Study.

Objective: It is unclear whether isolated cutaneous lupus erythematosus (CLE) affects cardiovascular risk. We estimated the cumulative incidence and mortality of cardiovascular diseases in a population-based CLE cohort and compared the risk with a matched non-CLE cohort.

Methods: All incident cases of CLE in Olmsted County, Minnesota, between 1965 and 2005 were followed until December 2013.

Epidemiology of Mixed Connective Tissue Disease, 1985-2014: A Population-Based Study.

Objective: To characterize the epidemiology of mixed connective tissue disease (MCTD) from 1983 to 2014.

Methods: An inception cohort of patients with incident MCTD in 1985-2014 in Olmsted County, Minnesota was identified based on comprehensive individual medical record review. Diagnosis of MCTD required fulfillment of at least 1 of the 4 widely accepted diagnostic criteria without fulfillment of classification criteria for other connective tissue diseases.

A Central Role for HLA-DR3 in Anti-Smith Antibody Responses and Glomerulonephritis in a Transgenic Mouse Model of Spontaneous Lupus.

MHC, especially HLA-DR3 and HLA-DR2, is one of the most important genetic susceptibility regions for systemic lupus erythematosus. Human studies to understand the role of specific HLA alleles in disease pathogenesis have been hampered by the presence of strong linkage disequilibrium in this region. To overcome this, we produced transgenic mice expressing HLA-DR3 (DRβ1*0301) and devoid of endogenous class II (both I-A and I-E genes, AE(0)) on a lupus-prone NZM2328 background (NZM2328.

Superantigens produced by catheter-associated Staphylococcus aureus elicit systemic inflammatory disease in the absence of bacteremia.

SAgs, produced by Staphylococcus aureus, play a major role in the pathogenesis of invasive staphylococcal diseases by inducing potent activation of the immune system. However, the role of SAgs, produced by S. aureus, associated with indwelling devices or tissues, are not known.

Pregnancy-related issues in women with systemic lupus erythematosus.

While fertility is preserved in females with systemic lupus erythematosus (SLE), it is well established that pregnancy in these patients is associated with adverse maternal and fetal outcomes, including pregnancy loss, pre-eclampsia, preterm delivery and intrauterine growth retardation, as well as neonatal mortality. Mechanisms underlying these adverse outcomes are poorly understood, and better understanding of these would allow development of targeted and personalized treatment strategies. Established risk factors for adverse pregnancy outcomes include active disease within 6 months prior to conception and during pregnancy, active nephritis, maternal hypertension, antiphospholipid antibodies and hypocomplementemia.

Epidemiology of systemic lupus erythematosus and cutaneous lupus erythematosus in a predominantly white population in the United States.

Objective: Epidemiologic studies comparing the incidence and prevalence of systemic lupus erythematosus (SLE) and isolated cutaneous lupus erythematosus (CLE) are few. Olmsted County, Minnesota provides a unique setting for such a study owing to resources of the Rochester Epidemiology Project. We sought to describe and compare the incidence and prevalence of SLE and CLE from 1993-2005.

Systemic inflammatory response elicited by superantigen destabilizes T regulatory cells, rendering them ineffective during toxic shock syndrome.

Life-threatening infections caused by Staphylococcus aureus, particularly the community-acquired methicillin-resistant strains of S. aureus, continue to pose serious problems. Greater virulence and increased pathogenicity of certain S.

CT angiographic imaging characteristics of thoracic idiopathic aortitis.

Background: Idiopathic aortitis (IA) is characterized by giant cell or lymphoplasmacytic inflammation of aorta without a secondary cause.

Objective: We undertook a retrospective case-control study to identify characteristic CT angiographic findings in these patients and to correlate them with known atherosclerotic risk factors.

Methods: IA cases and controls with noninflammatory aneurysm (control group I) and patients with secondary aortitis (control group II) were identified with a pathology database.

Chronic exposure to staphylococcal superantigen elicits a systemic inflammatory disease mimicking lupus.

Chronic nasal and skin colonization with superantigen (SAg)-producing Staphylococcus aureus is well documented in humans. Given that trans-mucosal and trans-cutaneous absorption of SAgs can occur, we determined whether chronic exposure to small amounts of SAg per se could activate autoreactive CD4(+) and CD8(+) T cells and precipitate any autoimmune disease without further external autoantigenic stimulation. Because HLA class II molecules present SAg more efficiently than do mouse MHC class II molecules, HLA-DQ8 transgenic mice were implanted s.

Autoimmune hepatitis: a review of current diagnosis and treatment.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. An environmental agent is hypothesized to trigger an immune-mediated attack directed against liver antigens in genetically predisposed individuals. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure, and diagnosis requires exclusion of other causes of liver disease.

Noninfectious ascending aortitis: a case series of 64 patients.

Objective: To identify the clinical presentation and histopathologic characteristics of noninfectious ascending aortitis.

Methods: A retrospective medical record and histopathology review was performed of patients with histologic evidence of active noninfectious aortitis who underwent ascending aortic aneurysm resection at Mayo Clinic between January 1, 2000, and February 28, 2006. Clinicopathologic features were recorded, including demographics, clinical presentation, laboratory, imaging findings, histopathology, complications, treatment, and outcome.

Cardiovascular risk factors and acute-phase response in idiopathic ascending aortitis: a case control study.

Introduction: Idiopathic aortitis is a rare condition characterized by giant cell or lymphoplasmacytic inflammation of the aorta. The purpose of this study was to describe risk factors for the development of idiopathic aortitis.

Methods: We conducted a case control study of 50 patients who were age-matched with two control subjects with non-inflammatory ascending aortic aneurysms.

Liver involvement in systemic lupus erythematosus: case review of 40 patients.

Objective: Subclinical liver involvement is frequent in systemic lupus erythematosus (SLE). We sought to determine the presence of endstage liver disease in patients with SLE.

Methods: We carried out a retrospective chart review of our cohort of patients with SLE.

HLA-DQ8 is a predisposing molecule for detergent enzyme subtilisin BPN'-induced hypersensitivity.

Several million individuals are exposed to agents in the workplace associated with atopy and asthma. Detergent enzymes have been implicated in occupationally induced hypersensitivity. However, the genetic susceptibility and T cell responses to detergent enzymes are undefined.