SEARCH · Search PubMed
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Explore the source record for details and available documents.
Apoptosis plays an important role in the recovery from glomerulonephritis. Moreover, aberrant apoptosis seems to contribute to lupus nephritis. This study compared the intensity of apoptosis in lupus and non-lupus mesangiocapillary glomerulonephritis. We used an in situ cell death detection kit, POD, which detects single cell apoptosis in formalin-fixed renal tissue. Our material comprised 13 renal biopsy specimens from patients with lupus mesangiocapillary glomerulonephritis (SLE-N IV), 11 renal tissues from patients with non-lupus mesangiocapillary type I glomerulonephritis (MCGN) and 8 normal kidney samples. We checked the correlations between intraglomerular apoptotic cells and the total number of intraglomerular cells, the relationship between tubulointerstitial apoptotic cells and the relative interstitial cortical volume. The population of intraglomerular apoptotic cells was lower in tissues from SLE-N IV patients than patients with MCGN. In MCGN the intensity of apoptosis in glomeruli correlated significantly with the number of total glomerular cells. Tubulointerstitial apoptotic cells were infrequent in the kidney samples from patients with SLE-N IV and in the normal kidney. In the renal interstitium and tubuli the number of apoptotic cells did not correlate with the relative interstitial cortical volume in kidney tissue in patients with MCGN. In the biopsies from patients with SLE-N IV there was an inverse correlation between tubulointerstitial apoptotic cells and the relative interstitial cortical volume, so a low number of apoptotic tubulointerstitial cells was associated with fibrosis in the renal interstitium. The results illustrate the differences in the intensity of apoptosis in lupus and non-lupus glomerulonephritis. The low number of apoptotic cells in renal tissue from patients with SLE-N IV suggests regulation of apoptosis may be altered in the mechanisms of glomerular and tubulointerstitial damage in lupus nephritis, although the reduced apoptosis may simply be due to smaller numbers of cells in fibrotic areas.
We prospectively studied 91 infants born to women with systemic lupus erythematosus (SLE) or with SLE-like disease. Thirty-eight infants, including 3 sets of twins, were born to women who had anti-Ro, anti-La, or anti-RNP antibodies. Four infants had definite neonatal lupus, and 4 had possible neonatal lupus. No prospectively studied infant had congenital heart block. The presence of neonatal lupus did not correlate with the titer of anti-Ro antibodies. During the same time period, 2 additional babies with neonatal lupus and congenital heart block were born to mothers not previously known to have SLE. Taken together, these findings confirm the association of anti-Ro antibody with neonatal lupus, but indicate that life-threatening neonatal lupus is rare in children born to mothers who are known to have SLE, even when antibodies to Ro, La, or RNP are present. Prophylactic therapy is therefore not indicated for these women. An important proportion of mothers bearing children with neonatal lupus do not have recognized SLE and, currently, cannot be prospectively identified.
We studied the clinical course of 59 lupus patients with end-stage renal disease (ESRD) to determine their long-term prognosis and delineate the evolution of their lupus activity. The study population was predominantly female (86%) and young (mean age, 27.4 years), and they were observed for a mean of 6.5 years from the inception of dialysis. At the time dialysis was initiated, only 21 patients (35.6%) had clinically active systemic lupus erythematosus (SLE). The remaining patients progressed to ESRD despite the absence of clinical lupus activity. Lupus activity was clinically apparent in 55.4% of patients in the first year, 6.5% in the fifth, and none in the tenth year. In 45% of patients, lupus activity was clinically inactive at entry to ESRD and remained inactive throughout the observation period. Serological activity declined proportionally, but to a lesser extent than clinical activity. Cumulative patient survival was 81.1% and 74.6% at the fifth and tenth year, respectively, from the inception of dialysis treatment; similarly it was 78% at the fifth and tenth year after the transplantation. Graft survival was 60.4% at the fifth and 45.5% at the tenth year. No one had recurrence of clinical lupus nephritis in the graft for up to 16 years of follow-up. Fourteen patients died from either infectious or cardiovascular complications, but none from SLE per se. This long-term study with a large number of lupus patients confirms our previous findings that the progression of renal disease to ESRD may be mediated by nonimmunologic mechanisms, as well as immunologic insults.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVE: To study 5 type I interferon (IFN)-inducible genes (LY6E, OAS1, OASL, MX1, and ISG15) in patients with systemic lupus erythematosus (SLE) and to correlate expression levels with disease activity and/or clinical manifestations. METHODS: Peripheral blood cells were obtained from 48 SLE patients, 48 normal controls, and 22 rheumatic disease controls, and total RNA was extracted and reverse transcribed into complementary DNA. Gene expression levels were measured by real-time polymerase chain reaction, standardized to a housekeeping gene, and summed to an IFN score. Disease activity was determined by the Safety of Estrogens in Lupus Erythematosus: National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) composite. RESULTS: Each gene was highly expressed in SLE patients compared with normal controls (P < or = 0.0003) or disease controls (P < or = 0.0008 except for MX1). IFN scores were positively associated with the SELENA-SLEDAI instrument score (P = 0.001), the SELENA-SLEDAI flare score (P = 0.03), and the physician's global assessment score (P = 0.005). Compared with patients without nephritis, lupus nephritis patients had higher IFN scores (overall P < 0.0001), especially during active renal disease. IFN scores were weakly associated with neurologic manifestations. Elevated IFN scores were positively associated with the current presence of anti-double-stranded DNA (anti-dsDNA) antibodies (P = 0.007) or hypocomplementemia (P = 0.007). LY6E expression levels distinguished active from inactive lupus nephritis (P = 0.02) and were positively associated with proteinuria (P = 0.009). CONCLUSION: The 5 IFN-inducible genes were highly expressed in SLE patients, and increased levels were correlated with disease activity defined by several methods. IFN scores, or LY6E levels, were elevated in lupus nephritis patients, especially during active renal disease, and in patients with anti-dsDNA antibody positivity and hypocomplementemia. IFN scores, or LY6E levels, may be useful as a biomarker for lupus nephritis therapy.
The present study reviews the course of lupus nephritis (LN) with the added complication of neuropsychiatric systemic lupus erythematosus (NPSLE) in a predominantly African-American population in order to identify the risk factors accounting for the increased morbidity and mortality in African-American children. Previous studies, including those at our center, have demonstrated the poor prognosis for African-American children with LN. A possible factor is the involvement of the central nervous system (CNS), resulting in a heightened risk of morbidity, although to date there are no reports suggesting an association between NPSLE and patient and renal survival in children with lupus nephritis. To this end, we retrospectively analyzed charts of 72 children with lupus nephritis seen at our center from 1965 to 1999. These 72 patients formed two groups, with group 1 consisting of patients with lupus nephritis and NP manifestations and group 2 only lupus nephritis. We then examined various demographic factors such as age, sex and race along with the histopathologic class of lupus nephritis, occurrence of hypertension, incidence of end stage renal disease (ESRD), time to ESRD and mortality in both groups with the aid of Fisher's exact t-test and the chi-square test. Briefly, the results revealed significantly higher class III or IV histopathologic lesions on biopsy, incidence of hypertension, progression to ESRD and mortality in children with NPSLE and LN (group 1) compared to LN alone (group 2) in spite of aggressive immunosuppressive therapy. In conclusion, we report that NPSLE with LN is associated with an increased rate of ESRD and mortality in our predominantly African-American children.
Among the various autoantibodies commonly found in women with systemic lupus erythematosus, the so-called lupus anticoagulant has been described in association with fetal losses. Recently, women with repeated spontaneous abortions and lupus anticoagulant, but no apparent systemic lupus erythematosus have been described. We have studied prospectively the possible connections between fetal losses and autoimmunity in a large control study of 130 idiopathic habitual aborters. These non-pregnant patients without any antecedent autoimmune disease were explored for the presence for autoantibodies especially lupus anticoagulant. Ten percent of the patients exhibit an antithromboplastin antibody (lupus anticoagulant) and half of this group possesses a striking association of biological manifestations of autoimmunity. In conclusion, two points appear: firstly, statistical correlation is demonstrated between antithromboplastin antibody and habitual abortion; secondly, doubt remains about the significance of the association between autoimmunity, fetal losses and antithromboplastin: beginning of systemic lupus erythematosus or new autoimmune entity with gynaeco-obstetrical expression.
Subacute cutaneous lupus erythematosus (SCLE) was originally described and distinguished from discoid lupus erythematosus (DLE) on the basis of clinical examination of the skin, but subsequent reports have questioned the concept of SCLE as a marker of a unique subset of LE patients. We classified 27 lupus patients, on the basis of cutaneous exam, as having discoid lupus skin lesions, subacute cutaneous skin lesions, or systemic lupus erythematosus (SLE) without DLE or SCLE lesions. Clinical features most characteristic of SCLE rather than DLE were superficial, non-indurated, non-scarring lesions, and photosensitivity, with lack of induration being the single most helpful finding. Histologic examination of lesional skin showed a relatively sparse, superficial infiltrate in SCLE and a denser, deeper infiltrate in DLE. A distinctive pattern of staining with direct immunofluorescence, particulate epidermal IgG deposition, was found in seven of seven SCLE patients (all anti-Ro/SSA positive) and none of the other patients. This distinctive pattern can be reproduced experimentally when anti-Ro/SSA autoantibodies are infused into human skin-grafted mice. Particulate dermal-epidermal junctional staining was the pattern seen in the patients who did not have SCLE. Clinically defining SCLE as a superficial inflammatory form of cutaneous lupus (i.e., considering lesions to be DLE if they are indurated) results in a meaningful segregation of SCLE and DLE patient groups. The epidermal IgG deposits unique to SCLE provide independent evidence that the clinical findings that were used to identify the patient groups actually identify distinctive cutaneous lupus subsets. The observation that antibodies are present in a different location in the skin in SCLE than in DLE indicates that SCLE and DLE are likely to have different pathomechanisms.
OBJECTIVE: The sensitivity and specificity of the lupus band test was evaluated, using three different criteria, on sun-protected non-lesional skin for the diagnosis of systemic lupus erythematosus (SLE). In addition, the sensitivity and specificity of the lupus band test was compared with those of other laboratory tests used in the diagnosis of SLE. METHODS: Sun-protected non-lesional skin biopsies from 65 patients (F 50; M 15; mean age 41 yrs.) with specific cutaneous manifestations of lupus erythematosus (LE) and from 18 patients with other dermatologic diseases (F 11, M 7; mean age 40 yrs.) were tested using the direct immunofluorescent technique. RESULTS: The sensitivity and specificity of the lupus band test was 10.5% and 97.8% respectively using the strict criterion of the presence of two different immunoreactants. The sensitivity and specificity were 52.6% and 69.5% respectively based on the presence of two different immunoreactants and were 78.9% and 47.8% based on the presence of only one immunoreactant. The highest sensitivity was found for ANA (100%). The specificity of all the laboratory abnormalities was particularly high, varying from 82.8% to 100%, except for ANA antibodies which showed a specificity of 65.2%. CONCLUSIONS: A positive lupus band test on sun-protected non-lesional skin (even if showing the presence of only one immunoreactant at the dermo-epidermal junction) represents a useful and specific criterion for identifying patients with LE. However, this test is not useful in distinguishing between cutaneous lupus patients with systemic involvement and those without systemic involvement.
Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis, further increasing the risk of athero-thrombotic cardiovascular complications.
OBJECTIVE: There is evidence that estrogens play a role in the etiology of systemic lupus erythematosus (SLE), but this has not yet been shown for discoid lupus. We examined the association of postmenopausal estrogen use with the development of SLE and discoid lupus. METHODS: We did a case-control evaluation, using the UK based General Practice Research Database. We analyzed 41 cases with SLE, 34 cases with discoid lupus, and 295 age, sex and practice matched controls, and estimated relative risk estimates (odds ratios) in relation to estrogen exposure duration as well as total cumulative dose and estrogen type (alone or combined with progestogens). RESULTS: While short term estrogen exposure was not associated with increased risk, the risk of developing SLE (adjusted OR 2.8; 95% CI 0.9-9.0) or discoid lupus (adjusted OR 2.8; 95% CI 1.0-8.3) was significantly increased among current users who were exposed for 2 or more years. The adjusted RR estimate comparing longer term estrogen users and nonusers for all cases (SLE and discoid lupus combined) was 2.8 (95% CI 1.3-5.8; p < 0.01). A difference was found between longterm users of estrogens alone (OR 5.3; 95% CI 1.5-18.6) and those who used estrogens combined with progestogens (OR 2.0; 95% CI 0.8-5.0), compared to nonusers. CONCLUSION: Our findings suggest that longer term use of postmenopausal estrogens plays a role in the etiology of both SLE and discoid lupus. There is a suggestion that progestogens may reduce the effect of estrogens on these autoimmune disorders.
Lupus panniculitis is a rare variant of cutaneous lupus erythematosus. Two typical cases demonstrate the association of lupus panniculitis with signs of discoid lupus erythematosus and systemic lupus erythematosus. Clinically it is characterised by subcutaneous nodules or plaques, which may ulcerate leaving depressed atrophic scars. Histologically the lesions show lobular panniculitis. A positive immunofluorescent band test with deposition of IgG, IgM and C3 at the dermal-epidermal junction and blood vessel walls helps to confirm the diagnosis. The knowledge of the clinical features and histopathology of the disease is important because lupus panniculitis may precede systemic lupus erythematosus by some years.
The assessment of disease activity in systemic lupus erythematosus (SLE) is a task faced by clinicians in every day care, but it is also required for clinical research and in randomised controlled trials. It is crucial to distinguish disease activity from infection, chronic damage and co-morbid disease. Over the past 20 years, many indices have been developed to objectively measure lupus disease activity and several of these have been validated. The most widely used indices are the British Isles Lupus Assessment Group (BILAG) index, the European Consensus Lupus Activity Measurement (ECLAM), the Systemic Lupus Activity Measure (SLAM), the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Lupus Activity Index (LAI). All these indices have been validated and have excellent reliability, validity and responsiveness to change. In addition to the assessment of disease activity, the evaluation of damage using the validated SLICC/ACR damage index and health-related quality of life is advised for clinical research.
OBJECTIVE: To determine the incidence of and risk factors for hospitalization in systemic lupus erythematosus (SLE). METHOD: A prospective study of hospitalizations in 1989 and 1990 in the Hopkins Lupus Cohort was conducted. RESULTS: Of 261 patients with SLE in the Hopkins Cohort, 147 (56.3%) were hospitalized in 1989 or 1990. The incidence of hospitalization was 0.69 admissions/person-year. The mean length of stay was 9.6 days +/- 12.7 (SD). Activity of SLE accounted for 35% of admissions. Risk factors for hospitalization for active lupus in 1990 included activity of SLE in 1989 (measured by either the highest physician's global assessment in 1989, p = 0.004, highest lupus activity index (LAI) score in 1989, p = 0.002, or highest systemic lupus erythematosus disease activity index score in 1989, p = 0.008), an average prednisone dose greater than 10 mg in 1989 (p = 0.002), and the presence of neurologic lupus in 1989 (p = 0.02). Medical admissions other than for active SLE accounted for an additional 27% of admissions; one-half of these admissions (47%) were for complications of SLE and/or its treatment, with coronary artery disease the most common (21% of medical admissions). Infections were responsible for 14% of admissions. The majority of infections were bacterial (90%). Risk factors for hospitalization for infection in 1990 included active SLE in 1989 (p = 0.03), average prednisone dose of greater than 10 mg in 1989 (p = 0.04), immunosuppressive drug use in 1989 (p = 0.003), neurologic SLE in 1989 (p = 0.02) and previous hospitalization in 1989 (p = 0.03). CONCLUSION: Hospitalization is common in the Hopkins Lupus Cohort, with active SLE (35%), infection (14%, infection and/or active SLE; 11%, infection alone) and medical complications of SLE (13%) as the 3 most common causes.
A 22 year old male of lupus nephritis associated with minimal change nephrotic syndrome was described. The patient was well until 4 years earlier, when Raynaud's phenomenon and photosensitivity developed. One week before admission, edema appeared suddenly and proteinuria was pointed out on July 28, 1990. On admission, his legs, ankles, and eyelids were edematous. There was no sclerodactylia, although Raynaud's phenomenon was positive when his hand disclosed to the cold. Urinalysis showed heavy albuminuria (10.4g/day), but urinary sediment showed no abnormality. Immunological examination showed positive antinuclear antibody, determination at a titer of 1: 160 with a speckled pattern. Anti-RNP and anti-Sm antibody were positive. However, neither anti-DNA antibody nor hypocomplementemia was detected. There was high concentration of serum IgE (2564IU/ml). Renal biopsy was performed. Light microscopic study showed slight increase of mesangial cells and matrix. Immunofluorescence study showed mesangial localization of IgG and C3. Electron microscopic study showed electron dense deposits only in the mesangial area. The diagnosis of lupus nephritis associated with minimal change nephrotic syndrome (MCNS) was made and administration of PSL was started. Proteinuria disappeared after 3 weeks and nephrotic syndrome remitted completely. The case of lupus nephritis associated with MCNS is very rare. Therefore, the relationship between amounts of proteinuria and various histological types of 67 cases with lupus nephritis which we experienced at our hospital was evaluated. Results showed that nephrotic range proteinuria was not present in mesangial lupus nephritis. So, it was concluded that if heavy albuminuria was found in mesangial lupus nephritis, we should consider the possibility of lupus nephritis associated with MCNS.
In the glomerulonephritides of systemic lupus erythematosus (SLE), the number of subendothelial deposits, when present, generally corresponds to the degree of light microscopic glomerular hypercellularity; only very rarely are no or few such deposits present in cases of focal (WHO class III) or diffuse (WHO class IV) proliferative lupus nephritis. We have recently encountered five cases of active diffuse proliferative glomerlonephritis with no subendothelial and few or no mesangial deposits and thrombotic microangiopathy (TMA) in four patients with SLE and one patient with lupus-like syndrome. Three of the five patients were tested for circulating lupus anticoagulants or anticardiolipin antibodies, and two were positive. All five patients tested negatively for antineutrophil cytoplasmic antibodies (ANCA). Three patients responded to steroid and cyclophosphamide treatment, although one of them died of acute bacterial bronchopneumonia. One patient was lost to follow-up. We conclude that "pauci-immune" proliferative lupus nephritis is rare and should be treated as proliferative lupus nephritis with a proportionate number of subendothelial deposits. The negative ANCA suggests that these cases do not represent incidental ANCA-associated pauci-immune necrotizing and crescentic glomerulonephritis in patients with SLE. Of particular interest is that, in patients with SLE, if associated with TMA, an active proliferative necrotizing glomerulonephritis may be present even in the absence of significant glomerular immune complex deposition.
Systemic lupus erythematosus is a multisystemic autoimmune disease. The immunopathogenesis is characterized by the loss of tolerance to self. While many abnormalities in the immune system have been detected, genetic factors play a central role in the pathogenesis. The event proximate to target organ involvement appears to be autoantigen-driven, T cell-mediated, B cell activation. High levels of autoantibodies are produced. However, not all autoantibodies are pathogenic to the kidney (i.e. 'nephritogenic'). These nephritogenic autoantibodies appear to share specific physiochemical features that correlate well with patterns of renal injury. While DNA was initially regarded as the inciting autoantigen, this view does not appear to be supported by the prevailing evidence. Nucleosomes, which are structures comprising histones and DNA, have emerged as the more likely candidate autoantigen. Autoantibodies directed against nucleosomes that cross-react with nucleosomal epitopes have been identified. Furthermore, evidence suggests that immunoglobulin-nucleosomal complexes may be important in target organ immune deposition. In-vivo generation of nucleosomes requires apoptosis; in fact, there are several examples of aberrant apoptotic processes that present with autoimmunity. Aberrant apoptosis may also be critical in lupus immunopathogenesis. Indeed, studies on Fas/FasL and Bcl-2 in animal models and in humans have underscored the importance of apoptosis as an etiological factor in lupus. Cytokines, hormonal, infectious and environmental factors have also been found to be important in the pathogenesis of systemic lupus erythematosus. Overall, much progress has been made in elucidating the etiological agents and pathogenic mechanisms by which lupus develops. However, there is still some way to go before arriving at a unifying hypothesis. The reward for a better understanding of lupus immunopathogenesis will be the development of more specific targets for treatment, and the introduction of better and safer treatment modalities.
The lupus anticoagulant was found in the plasma of 31 of 60 patients with systemic lupus erythematosus and other connective tissue disorders (mixed connective tissue disease, systemic vasculitis, polyarteritis nodosa, primary sicca syndrome, discoid lupus, Behcet's syndrome, and systemic sclerosis). Strong associations were found with biological false positive seroreaction for syphilis and thrombocytopenia. The most striking association, however, was with the high prevalence of thrombosis. This tendency to thrombosis was independent of disease activity of systemic lupus erythematosus. The lupus anticoagulant appears to be a useful marker for a subset of patients with systemic lupus erythematosus at risk for the development of thromboembolic complications.