Circulating 20S proteasome levels in patients with mixed connective tissue disease and systemic lupus erythematosus.

The associations of circulating 20S proteasomes (c20S) with clinical and serologic disease indices in patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are unknown. We present the initial report that c20S levels are elevated in MCTD and correlate with clinically relevant changes in disease activity in SLE and MCTD.

Immune pathogenesis of Mixed Connective Tissue Disease: a short analytical review.

Mixed Connective Tissue Disease (MCTD) was first described 35 years ago by Gordon C. Sharp and his colleagues. In the ensuing decades, a clearer understanding of the clinical and serologic features of MCTD has emerged. Classification criteria now exist to define MCTD for study purposes, the long-term outcome of the disease has been established, and novel genetic associations within the major histocompatibility complex on chromosome 6 and select regions on chromosome 3 have been identified. Studies on immune pathogenesis have made substantial progress in advancing our understanding of MCTD. In MCTD, there is a complex interaction of the innate and adaptive immune system that culminates in autoimmune disease. Antigenic structural modification occurring during apoptosis or other modifications of self antigens leads to an autoantigen driven immune process with innate immune activation, immunoglobulin G autoantibody production directed against select components of the spliceosome, B lymphocyte activation, and CD4 and CD8 T lymphocyte participation.

Clinical and immunologic manifestations of mixed connective tissue disease in a Miami population compared to a Midwestern US Caucasian population.

OBJECTIVE: A cross-sectional study of mixed connective tissue disease (MCTD) was performed to determine if there were identifiable differences in the clinical expression of MCTD associated with race or ethnicity. METHODS: Miami, Florida, and Midwestern US (Missouri) Caucasian MCTD cohorts were studied. Clinical and laboratory features of the 2 MCTD cohorts were compared. A concurrently collected cohort of Sm-positive patients with systemic lupus erythematosus (SLE) was studied as a control. Disease activity and severity and functional status were measured. CD4+CD25(high)-expressing T-regulatory cells were enumerated and serum soluble L selectin was measured as biomarkers of disease activity. RESULTS: The Miami and Missouri Caucasian MCTD groups, while differing from the SLE group, were largely similar; however, gastroesophageal reflux, sclerodactyly, and malar rash were significantly more frequent in the Missouri MCTD group and alopecia was more frequent in the Miami MCTD group. Significant clinical and laboratory differences were found between the Miami MCTD and Miami SLE groups despite similar disease duration, activity, severity and functional status. Raynaud's phenomenon (RP), hand swelling, synovitis, myositis, and sclerodactyly were all significantly more common in RNP-positive MCTD versus Sm-positive SLE subjects. CONCLUSION Ethnic differences were observed in the frequency of end-organ involvement in the Miami MCTD versus the Missouri Caucasian MCTD groups. Clinical and laboratory features of all MCTD groups were clearly different from the SLE group, despite similar disease activity, disease severity, and functional status. Disease activity measures appeared to behave similarly as valid measures of disease activity in SLE and MCTD.

The incidence and prevalence of neuropsychiatric syndromes in pediatric onset systemic lupus erythematosus.

OBJECTIVE: To determine the incidence and prevalence of neuropsychiatric systemic lupus erythematosus (NPSLE) and glomerulonephritis in ethnically diverse pediatric onset SLE inpatient and outpatient populations. METHODS: Seventy-five pediatric onset patients with SLE including Native American, Asian, Black, Spanish-American, and Caucasian subjects were evaluated prospectively and cross sectionally. During the 6 year study, 55 patients became inpatients. Subjects underwent medical interview, physical examination, laboratory review, neuropsychiatric inventory, and chart review. Classification of NPSLE was accomplished with the 1999 ACR NPSLE case definitions. RESULTS: Prospectively, NPSLE occurred in 95% of pediatric SLE patients and was more common than glomerulonephritis (55%; p < or = 0.0001). NPSLE prevalence (%) and incidence (event/person/yr) were as follows: headache 72%, 95; mood disorder 57%, 0.41; cognitive disorder 55%, 0.49; seizure disorder 51%, 0.94; acute confusional state 35%, 0.6; anxiety disorder 21%, 0.28; peripheral nervous system disorder 15%, 0.16; cerebrovascular disease 12%, 0.32; psychosis 12%, 0.16; chorea 7%, 0.01; demyelinating syndrome 4%, 0.01; and myelopathy 1%, 0.001. Cross sectionally, active NPSLE was present in 93% of inpatients and 69% of outpatients. When only serious forms of NPSLE were considered (stroke, seizures, major cognitive disorder, chorea, psychosis, major depression, acute confusional state), serious or life-threatening NPSLE occurred in 76% of all SLE subjects prospectively, and in 85% and 40% of inpatients and outpatients cross sectionally, which in each instance was more common than glomerulonephritis (p < or = 0.001). CONCLUSION: NPSLE is one of the most common serious complications of pediatric SLE, and is particularly increased in pediatric inpatients.

Neuropsychiatric systemic lupus erythematosus presenting as amyotrophic lateral sclerosis.

A 61-year-old woman with a history of photosensitive dermatitis and recurrent mouth ulcers presented with progressive weakness typical of amyotrophic lateral sclerosis (ALS), and subsequently underwent extensive neurologic and rheumatologic testing. We investigated whether ALS-like motor neuron disease associated with a positive antinuclear antibody (ANA) is really ALS or rather neuropsychiatric systemic lupus erythematosus (NPSLE). On neurologic evaluation, she had prominent bulbar involvement with dysarthria and dysphagia associated with profound lingual fasciculations and a denervating pattern on electromyogram. MRI showed no evidence of cerebral ischemia. Laboratory studies revealed a positive ANA (1:2560 titer), positive antiphospholipid antibodies (GPL and MPL), circulating lupus anticoagulant, and depressed C3 and C4. Repeat MRI studies at 4 and 11 mo revealed an evolving infarct in the paramedian pons consistent with the presence of NPSLE. Therapy was initiated with corticosteroids and intravenous cyclophosphamide, and the neurologic condition did not improve, but also did not progress inexorably as would be expected with ALS. NPSLE, presumably through the mechanism of ischemic vasculopathy, may present as motor neuron disease clinically indistinguishable from ALS.