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PubMed2007

Protein array autoantibody profiles for insights into systemic lupus erythematosus and incomplete lupus syndromes.

The objective of this study was to investigate the prevalence and clinical significance of a spectrum of autoantibodies in systemic lupus erythematosus and incomplete lupus syndromes using a proteome microarray bearing 70 autoantigens. Microarrays containing candidate autoantigens or control proteins were printed on 16-section slides. These arrays were used to profile 93 serum samples from patients with systemic lupus erythematosus (SLE (n = 33), incomplete LE (ILE; n = 23), first-degree relatives (FDRs) of SLE patients (n = 20) and non-autoimmune controls (NC; n = 17). Data were analysed using the significance analysis of microarray (SAM) and clustering algorithms. Correlations with disease features were determined. Serum from ILE and SLE patients contained high levels of IgG autoantibodies to 50 autoantigens and IgM autoantibodies to 12 autoantigens. Elevated levels of at least one IgG autoantibody were detected in 26% of SLE and 19% of ILE samples; elevated IgM autoantibodies were present in 13% of SLE and 17% of ILE samples. IgG autoantibodies segregated into seven clusters including two specific for DNA and RNA autoantigens that were correlated with the number of lupus criteria. Three IgG autoantibody clusters specific for collagens, DNA and histones, were correlated with renal involvement. Of the four IgM autoantibody clusters, two were correlated negatively with the number of lupus criteria; none were correlated with renal disease. The IgG : IgM autoantibody ratios generally showed a stepwise increase in the groups following disease burden from NC to SLE. Insights derived from the expanded autoantibody profiling made possible with the antigen array suggest differences in autoreactivity in ILE and SLE. Determining whether the IgM aurotreactivity that predominates in ILE represents an early stage prior to IgG switching or is persistent and relatively protective will require further longitudinal studies.

Adult↗
PubMed1991

Haemostatic factors associated with vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant.

To elucidate the mechanism of vascular thrombosis in patients with systemic lupus erythematosus and the lupus anticoagulant changes in factors associated with haemostasis were investigated. The lupus anticoagulant was associated with an increased incidence of thrombosis, particularly cerebral thrombosis. Concentrations of fibrinopeptide A and fibrinopeptide B beta 15-42 were significantly raised in the plasma of patients with systemic lupus erythematosus and the anticoagulant compared with concentrations in patients without the lupus anticoagulant. The tendency towards formation of thrombosis was not found in all lupus patients with the anticoagulant, however. Concentrations of thromboxane B2 were remarkably raised in the plasma of the two patients with the lupus anticoagulant who had recently had thrombosis. Concentrations of 6-keto-prostaglandin F1 alpha, protein C, antithrombin III, and plasminogen were similar in both groups. No significant decrease in serum stimulatory activity on prostacyclin production by cultured aortic endothelial cells was noted in lupus patients with the anticoagulant, but inhibition was present in the two patients with recent thrombosis. These results indicate that although patients with the lupus anticoagulant are not always in a hypercoagulable state, haemostatic abnormalities found in some patients with the anticoagulant may be predictive of thrombotic events.

6-Ketoprostaglandin F1 alpha↗
PubMed1994

Systemic disease in subacute cutaneous lupus erythematosus: a controlled comparison with systemic lupus erythematosus.

OBJECTIVE: We sought to compare the prevalence of systemic disease in subacute cutaneous lupus erythematosus (SCLE) with systemic lupus erythematosus (SLE). METHODS: Clinical and laboratory features of 14 patients with SCLE were compared with 22 age and sex matched controls with SLE. RESULTS: Manifestations other than arthritis and skin disease were present in 11/14 (79%) SCLE cases compared with 19/22 (82%) SLE cases. Severe systemic disease occurred in one-half of patients with SCLE (5/7 men, 1/7 women), and most had the papulosquamous pattern. CONCLUSION: Systemic manifestations may be as varied in SCLE as in SLE, and severe disease is not unusual. In particular, men with papulosquamous SCLE may be at higher risk for severe extracutaneous disease.

Adult↗
PubMed1989

Neonatal lupus erythematosus with a high anticardiolipin antibody titer. Unusual variant of neonatal lupus erythematosus or early-onset systemic lupus erythematosus?

A malar rash associated with severe gastrointestinal manifestations developed in a 4-month-old baby 3 months after a normal delivery. Serum complement and IgA levels were low during the active phase of the illness. An increased anticardiolipin antibody titer was demonstrated at the onset of disease and persisted for more than 6 months, at which time the skin and gastrointestinal manifestations subsided. The baby's mother, who had no symptoms, had an elevated Ro (SS-A) antibody titer and a moderately elevated anticardiolipin antibody titer.

Antibodies, Antinuclear↗
PubMed1999

Sensitivity of the Systemic Lupus Erythematosus Disease Activity Index, British Isles Lupus Assessment Group Index, and Systemic Lupus Activity Measure in the evaluation of clinical change in childhood-onset systemic lupus erythematosus.

OBJECTIVE: To investigate whether 3 disease activity indices commonly used to evaluate systemic lupus erythematosus (SLE) in adults are sensitive to clinical change in children, and thus suitable for the use in the management of childhood-onset SLE. METHODS: Thirty-five SLE patients who were newly diagnosed between 1993 and 1997, had an age at onset of 6-16 years (26 female and 9 male), and were currently being followed up at The Hospital for Sick Children (followup of 9 months to 4 years) were reviewed. The SLEDAI (Systemic Lupus Erythematosus Disease Activity Index), BILAG (British Isles Lupus Assessment Group index), and SLAM (Systemic Lupus Activity Measure) were applied at up to 4 occasions during the disease course: at the time of diagnosis, 6 months postdiagnosis, at the time of a flare (a deterioration in clinical presentation or laboratory results requiring initiation or increase of either corticosteroids or "second-line" drugs), and 6 months postflare. The sensitivity of the 3 measures to change, as gauged by the effect size (ES), effect size index (ESI), standard response mean (SRM), responsiveness statistic (RS), and relative efficiency index (REI), were compared. RESULTS: All 3 tools were very sensitive to change in disease activity (ES >0.8, ESI >2.3, SRM >0.6, RS >0.86, REI >0.72), but were ranked differently depending on the statistic used for comparison. CONCLUSION: All 3 measures of disease activity are highly sensitive to clinical change in children; none showed an overall superiority. The SLEDAI, BILAG, and SLAM can all be used to study response to treatment in children with SLE.

Adult↗
PubMed2004

Photosensitivity in lupus erythematosus.

BACKGROUND: Lupus erythematosus is a systemic disease process that may manifest with a variety of internal and cutaneous findings. Photosensitivity is one the most common manifestations of lupus erythematosus. In patients with lupus erythematosus, there is a relationship between exposure to ultraviolet light, autoantibodies, genetics and other factors in the development of photosensitivity. METHODS: Literature was reviewed on the topics of lupus erythematosus and photosensitivity discussed together and separately. The suggested mechanisms for their relationship were reviewed and analyzed. RESULTS: Photosensitivity's relationship to and influence on the systemic manifestations of lupus remain to be defined. Mechanisms for photosensitivity might include: modulation of autoantibody location, cytotoxic effects, apoptosis induction with autoantigens in apoptotic blebs, upregulation of adhesion molecules and cytokines, induction of nitric oxide synthase expression and ultraviolet-generated antigenic DNA. Tumor necrosis factor alpha also seems to play a role in the development of photosensitivity. CONCLUSION: The basis for photosensitivity in lupus has yet to be fully defined. It is more commonly associated with subacute and tumid lupus erythematosus than with other variants. Anti-Ro antibodies appear to relate to photosensitivity. Tumor necrosis factor alpha polymorphisms appear to be important in some variants of lupus with photosensitivity. There is no sine qua non antibody or mutation of photosensitivity in lupus. In patients with lupus, more work needs to be done to define the mechanisms of photosensitivity.

Apoptosis↗
PubMed1993

Abnormalities in the regulation of variable region genes that encode for antibodies to DNA may be a central factor in the pathogenesis of systemic lupus erythematosus.

Systemic lupus erythematosus (lupus) is characterised by the excessive and spontaneous production of antibodies to DNA. In animal models of lupus, and in humans, antibodies to DNA have been directly implicated in pathogenesis. The variable region genes that encode for reactivity of antibodies to DNA have, in general, not been regarded as a risk factor in lupus. Recent evidence from several workers, including ourselves, does not sustain this dogma. Individual autoreactive V genes appear to be repeatedly used and to have an affinity for DNA. These genes are present in subjects with the disease and in some, but not all, normal subjects. Presumably, in some subjects carrying autoreactive V genes in their germline, these genes are normally silenced by regulatory factors, including cytokines, and in others with disease there is a breakdown in regulation. Experimental evidence suggests that multiple cytokines may have a role and that this role is complex.

Animals↗
PubMed2006

Determinants of patient survival in systemic lupus erythematosus--focusing on lupus nephritis.

INTRODUCTION: Systemic lupus erythematosus is more prevalent among Asians, African Americans, and Hispanics than in Caucasians. Progress in its management over the past few decades has resulted in improved patient survival, although a considerable proportion of patients are still afflicted with long-term illnesses such as chronic renal failure secondary to lupus nephritis. METHODS AND RESULTS: This is a review of the factors that affect the survival of patients with systemic lupus erythematosus, including discussion of the measures that can further improve the clinical outcomes and prevent long-term complications. Recent advances in the treatment of severe lupus nephritis are emphasized, especially with regard to the minimization of treatment-related adverse events. CONCLUSIONS: While the prognosis of patients with severe lupus manifestations continues to improve, prevention of relapse remains a clinical challenge. Concomitant attention to health economics and sociopolitical issues is required to ensure that all patients can benefit from scientific progress in the understanding and treatment of severe lupus erythematosus.

Adrenal Cortex Hormones↗
PubMed1985

Systemic lupus erythematosus in patients with chronic cutaneous (discoid) lupus erythematosus. Clinical and laboratory findings in seventeen patients.

The presence of the discoid lupus erythematosus (DLE) skin lesion in a patient with systemic lupus erythematosus (SLE) has been suggested to be a marker of less frequent and less severe renal disease. The clinical and laboratory features of seventeen patients who were seen in a dermatology practice and who had DLE as a manifestation of SLE (DLE-SLE) are reported. DLE preceded the diagnosis of SLE in eight patients. In six patients, the onset was concurrent, whereas in three the SLE was present prior to the discoid skin lesions. Five of the patients had lesions of subacute cutaneous lupus erythematosus (SCLE), and Raynaud's phenomenon occurred in eight patients. Clinical evidence of a renal abnormality was present in six patients (hematuria in three, proteinuria in five, and abnormal renal function in two). Antibodies to nuclear and/or cytoplasmic components were abnormal in all patients. Antibody subsets did not correlate well with clinical findings; only half of those with Raynaud's phenomenon demonstrated a positive ribonucleoprotein; only one patient with SCLE demonstrated anti-Ro (SSA) antibody, but four of the six patients with a renal abnormality had an elevated anti-native deoxyribonucleic acid antibody titer. The cutaneous lesions were eventually widespread in all patients, although two had initial disease that was localized to the head and neck. Although renal disease occurs in this group, it is less common and usually milder than in previous groups of unselected SLE patients.

Adult↗
PubMed2002

Tumid lupus erythematosus.

Tumid lupus erythematosus (TLE) is a variant of cutaneous lupus erythematosus. Most patients who present with these skin lesions are young women. The condition clinically resembles polymorphous light eruption, systemic lupus erythematosus (SLE), reticulated erythematous mucinosis, or gyrate erythema. Histopathologically, the lesions resemble classic lupus erythematosus because of their superficial and deep lymphohistiocytic inflammatory infiltrates and dermal mucin. However, unlike classic lupus erythematosus, there is little or no epidermal or dermo-epidermal involvement. Antinuclear antibody test results are usually negative. We describe 4 cases of TLE and discuss the differential diagnosis.

Adult↗
PubMed1993

Bullous systemic lupus erythematosus. Report of a case with lupus erythematosus cells in the dermis.

A 20-year-old black patient with bullous systemic lupus erythematosus developed papular and vesicular lesions on the extensor surfaces of the extremities. Histologically, subepidermal blisters and papillary neutrophilic abscesses with a striking number of lupus erythematosus cells were observed. No circulating anti-basal-membrane-zone antibodies were found. By Western immunoblotting, the patient's serum showed no reactivity against epidermal or dermal extracts.

Adult↗
PubMed2002

Hair dye treatment use and clinical course in patients with systemic lupus erythematosus and cutaneous lupus.

The etiological role of hair dye treatment (HDT), some of them such as permanent hair dyes containing aromatic amines, in the development of SLE has been previously ruled out. However, the possible influence of HDT use on the course and prognosis of lupus patients has been assessed only in one short-term study. Since HDT is very extensive among the population, the knowledge of this possible negative effect may be very important. Thus, the aim of this study was to assess the long-term influence of several HDTs on the course and clinical severity of patients with both systemic lupus erythematosus (SLE) and cutaneous lupus (CL). In this longitudinal case series study, 91 SLE patients and 22 CL patients were prospectively studied from October 1988 to May 2000. They were divided into three groups: (a) non-HDT users--patients who have never used HDT (n = 65); (b) P-HDT users--HDT permanent type users, alone or in combination with other types of HDT (n = 28); (c) non P-HDT--users of other treatments different from permanent tinting (bleach, lowlights, etc; n = 20). In each patient we determined: (1) number of flares/year in SLE patients and worsening of cutaneous lesions for CL; (2) Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index; (3) predominant damaged organs/systems according to the HDT use and type of HDT; and (4) subjective impression about the disease evolution in relation to HDT use. No significant differences were found with respect to flares/year and SLICC/ACR damage index between the study groups. Non-HDT group presented more renal involvement and serositis than both HDT-user groups. No patient related the HDT use to the worsening of his disease. Therefore, in this study no evidence of an association between the long-term use of several types of HDT and the clinical activity and course of SLE and CL was found.

Adult↗