The autoantibody profile and disease activity in patients with systemic lupus erythematosus

Antinuclear antibodies are a group of autoantibodies which are typical for collagenous diseases. By means of the autoantibody profile different sub-groups of systemic lupus erythematosus (SLE) can be identified. This can serve as a certain prognostic factor of the affection. Patients with a negative antibody profile have fewer clinical and laboratory manifestations of SLE. Profile A (anti-dsDNA and/or anti-Sm has, as compared with patients with a negative antibody profile, more frequent organ manifestations. Patients with profile B (anti-RNP) have a higher frequency of Raynaud's phenomenon. Profile C (anti-Ro, anti-La) is characterized in particular by photosensitivity of the skin and secondary Sj?gren's syndrome. Profile D (antibodies against centromeres and/or Scl-70) are found in subjects with SLE with traits of scleroderma. Finally profile E (antibodies against histones) are found in SLE induced by drugs. In the submitted study in 28 patients with SLE autoantibodies anti-dsDNA, anti-DNP, extracted nuclear antibodies (ENA-Sm,Ro,La, histones, Sm/RNP, Scl-70) were evaluated and different subgroups of SLE were assessed. Attention was paid to their common characteristics and the activity of the disease. Associations of clinical activity of the disease expressed by the ECLAM index (European Consensus Lupus Activity Measurement) were tested as well as anti-dsDNA levels and also the association of the disease activity with C3 and C4 constituents of complement, CRP and circulating immunocomplexes in serum. Positivity of the antinuclear factor (ANF) was found in 21 patients, while in 7 subjects who were in clinical and laboratory remission, ANF was negative. A negative antibody profile was recorded in 9 patients, profile A was found in 13, 1 patient had profile B, and 4 patients had profile C. Antibody profile D was not found in the group. When using regression analysis and Pearson s correlation coefficient, correlations were found between anti-dsDNA values and the system ECLAM (r = 0.72, p < 0.01), anti-dsDNA and C3 levels (r = -0.59, p < 0.01), C4 (r = -0.50,, p < 0.01), and between the ECLAM system and C3 (r = -0.60, p 0.01) and C4 (r = -0.52, p < 0.01) and also between C3 and C4 mutually (r = 0.72, p < 0.01). From the submitted investigation ensues that investigation of antinuclear antibody levels in SLE is important not only for assessment of the diagnosis of the disease and its activity but also for assessment of the subgroups of the disease and for prediction of its development. As to other indicators of activity, assessment of the C3 and C4 constituents of complement is still important.     

Prolactin modulates the disease activity of systemic lupus erythematosus accompanied by prolactinoma

We report a 77-year-old man who developed Candida parapsilosis infection following total knee arthroplasty. Knee joint effusion was noted 2 weeks after surgery, and repeated cultures of aspirated fluid established the diagnosis of Candida parapsilosis infection 4 weeks after surgery. Treatment consisted of debridement and lavage of the involved joint together with continuous irrigation with fluconazole for 4 weeks, followed by oral fluconazole for another 6 months. At 3 years follow-up, the patient was doing well and radiological examination of the affected knee showed a firm attachment of the prosthesis. We suggest that early identification of the causative organism followed by continuous irrigation and use of appropriate antifungal medication may prevent joint instability and spares the removal of the prosthesis.     

Improvement of systemic lupus erythematosus activity by the association of delayed onset Cushing's syndrome

We describe a 43-year-old woman with systemic lupus erythematosus (SLE) who had complete resolution of all SLE symptoms as a result of hypercortisolemia induced by a glucocorticoid-producing adenoma of the left adrenal gland. After an adrenalectomy, she developed an SLE exacerbation, characterized by photosensitivity, polyarthralgia, and hemolytic anemia, which required intensive steroid therapy. This is the first report of a patient with SLE entering apparent remission due to excessive adrenal secretion of glucocorticoids.     

Correlation of 9G4 idiotope with disease activity in patients with systemic lupus erythematosus

OBJECTIVE: To compare the levels of the 9G4 idiotope (9G4 Id) in systemic lupus erythematosus (SLE) patients with a detailed disease activity index, the British Isles Lupus Assessment Group (BILAG) index, and serological parameters of disease activity by ds DNA antibody levels and serum C3 concentrations. METHODS: In a cross sectional analysis serum samples from 190 patients with SLE were studied and a further 55 serial bleeds from 14 patients. An enzyme linked immunosorbent assay was used to measure the 9G4 Id, and anti dsDNA and antimyeloperoxidase (MPO) antibodies. The C3 levels were measured by laser nephelometer. RESULTS: Seventy six of 190 (40%) of the patients tested had raised 9G4 Id levels. In the cross sectional study 9G4 Id levels were found to correlate with disease activity in the BILAG cardiovascular/respiratory renal, and haematological systems and with global BILAG score (p < 0.01). In the serial bleeds 9G4 Id levels correlated with anti-dsDNA antibody and C3 levels, but not with anti-MPO antibodies. No correlations were found with treatment. In six cases the 9G4 Id levels correlated well with global BILAG scores and dsDNA antibody levels. In four cases the BILAG global and 9G4 Id levels alone correlated well. CONCLUSIONS: Raised levels of the 9G4 Id are present in a substantial proportion of serum samples from patients with lupus, correlate with various aspects of disease activity in SLE. The Id is detectable on anti-dsDNA antibodies, though it must also be present on other immunoglobulins whose specificities remain unknown.     

Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity

OBJECTIVE: To assess nucleosome plasma levels in patients with systemic lupus erythematosus (SLE) and to study the correlations with serum antinucleosome, anti-double-stranded DNA (anti-dsDNA), and antihistone antibody activities, as well as with disease activity (by the SLE Disease Activity Index [SLEDAI]). METHODS: In a cross-sectional study, we assessed 58 SLE patients for their plasma nucleosome levels. Plasma nucleosome levels as well as serum antinucleosome, anti-double-stranded DNA, and antihistone antibody activities were assessed by enzyme-linked immunosorbent assay. SLE activity was evaluated using the SLEDAI: RESULTS: The mean (+/-SD) plasma nucleosome concentration in SLE patients was 52 +/- 159 ng/ml (range 5-1,180), and was significantly higher than that of the controls (16 +/- 8.8 ng/ml, range 8-52; P = 0.03). Thirteen of the 58 lupus patients had levels over the range of normal (defined as the control mean + 3 SD, or 42 ng/ml). An inverse correlation was found between nucleosome plasma levels and serum antinucleosome antibody activity in the entire group of SLE patients, those with active disease, and those with inactive disease, respectively. No correlation was found between the SLEDAI and nucleosome plasma concentrations. CONCLUSION: Nucleosome plasma levels may be normal or increased in SLE, and found in patients with active or inactive SLE. Longitudinal studies are needed to further establish whether high levels of circulating nucleosomes may predict the occurrence of an SLE flare.     

Depressive symptoms in patients with systemic lupus erythematosus: association with central nervous system lupus and Sj?gren's syndrome

OBJECTIVE: To determine if patients with systemic lupus erythematosus (SLE) with depressive symptoms differ in regard to organ involvement and serological activity from other patients with SLE. METHODS: Disease manifestations were compared between 71 patients with SLE with a history of depressive symptoms and 278 patients without a history of depressive symptoms by univariate analysis and multiple logistic regression. RESULTS: Both univariate and logistic regression analysis revealed an association of depressive symptoms with neuropsychiatric lupus and secondary Sj?gren's syndrome (SS). Patients with neuropsychiatric lupus had an adjusted odds ratio of 3.43 (95% CI 2.55, 4.63; p = 0.00005), and patients with secondary SS had an adjusted odds ratio of 2.97 (95% CI 2.08, 4.25; p = 0.0006) for depressive symptoms. No other organ involvement or serological abnormality was associated with depressed mood. CONCLUSION: These discrete associations of depressive symptoms with neuropsychiatric lupus and secondary SS suggest that depression does not occur purely as a response to social stresses, and may be a manifestation of autoimmune disease in some patients.     

Indicators of disease activity, prognosis, and treatment of systemic lupus erythematosus

Several instruments have been developed to assess disease activity in systemic lupus erythematosus. Any study of a new laboratory measure, any therapeutic trial, and any study of outcome and prognosis should include one of these validated measures of disease activity. The treatment of lupus is far from ideal. A controlled trial of plasmapheresis showed no benefit over standard regimens in lupus nephritis. A long course of pulse cyclophosphamide was shown to be better than pulse methylprednisolone or a short course of intravenous pulse cyclophosphamide. Despite the lack of ideal therapy, the prognosis of lupus, including 15-year survival rates, has improved over the past 4 decades. Specific organ damage continues to be an issue. Infection and vascular disease have emerged as important factors. With improved survival, other outcome measures, including specific organ function and health status, must be considered.     

dsDNA-, nucleohistone- and DNASE I-reactive T lymphocytes in patients affected by systemic lupus erythematosus: correlation with clinical disease activity

OBJECTIVE: To demonstrate the involvement of T lymphocytes reactive to autoantigens in the pathogenesis of autoimmune diseases and to analyse their clinical relevance. METHODS: The frequency of T cell clones reactive to double strand DNA (dsDNA), Nucleohistone (NH) complex and Dnase I was calculated for the peripheral blood mononuclear cells (PBMC) of 15 SLE patients and 9 healthy subjects by proliferation assay. RESULTS: DsDNA- and NH-specific T cell clones were found in the majority of the patients analysed (frequency ranging from 2 to 50 clones/10(7) PBMC), while their absence or very low frequency (2 clones/10(7) PBMC) was observed in the control PBMC. Their frequency significantly correlated with decreased serum concentrations of C3 and C4 and with the systemic lupus erythematosus disease activity index (P = 0.03). A very low frequency of Dnase I-reactive T cell clones was observed in both SLE and healthy subjects. CONCLUSION: Our results suggest that dsDNA- and NH-reactive T lymphocytes may be involved in the pathogenesis of SLE and that their quantification in the peripheral blood of patients could be a useful tool to follow the clinical course of the disease.     

Decreased production of TGF-beta by lymphocytes from patients with systemic lupus erythematosus

TGF-beta has marked inhibitory effects on the immune system but also serves as a costimulatory factor in the development of T cells with down-regulatory activities. This cytokine is secreted as a latent complex and converted extracellularly to its active form. We have recently learned that anti-CD2 is a potent inducer of lymphocyte-derived TGF-beta and that NK cells are the predominant source. The objective of this study was to compare levels of constitutive, anti-CD2-induced and cytokine-regulated TGF-beta produced by blood lymphocytes from patients with systemic lupus erythematosus (SLE) in comparison with healthy controls. Using a highly sensitive and specific bioassay to assess TGF-beta, we report that unstimulated PBL from SLE patients, especially the NK cell subset, produced decreased levels of active TGF-beta. In response to anti-CD2, concentrations of active and total TGF-beta were also decreased in SLE. After learning that IL-2 and TNF-alpha enhance lymphocyte production of active TGF-beta, we found that the addition of these cytokines was unable to increase active TGF-beta to normal concentrations. Although we observed that IL-10 inhibited the production of active TGF-beta, antagonism of this cytokine was unable to completely correct the defect. In two SLE patients with B cell hyperactivity, spontaneous IgG production was almost abolished by the combination of TGF-beta and IL-2. Therefore, decreased production of each of these cytokines in SLE could be important in the perpetuation of B cell hyperactivity.     

The level of serum thymic activity in patients with rheumatoid arthritis and systemic lupus erythematosus

Thymic serum activity (TSA) has been studied in 52 healthy subjects, 48 rheumatoid arthritis patients and 17 sufferers with systemic lupus erythematosus aged from 18 to 70. TSA was compared in patients under and over 40 years. In those under 40 TSA appeared significantly inhibited, while in older subjects it did not differ from age-matched control. No correlations were reported between TSA levels and clinical characteristics. Changes in TSA levels may be related both to low content of thymic hormones and formation of inactive complexes from thymic mediators with inhibitors.     

Reduction of pleural fluid complement activity in patients with systemic lupus erythematosus and rheumatoid arthritis

In this paper the author gives a survey and a classification of 642 cases of narcolepsy and hypersomnia which he himself studied in the course of 26 years. 368 cases were classified as narcolepsy, 274 as hypersomnia. The author further classifies narcolepsies according to their etiology, clinical form and pathophysiological mechanisms of origin. Hypersomnias are divided by the author into the symptomatic and the functional groups. According to the author it is useful to distinguish "short cycle hypersomnia", i.e. those with short duration of sleep attacks (hours) and intervals, from "long cycle hypersomnia", i.e. those with long attacks (days or weeks) and intervals. The author goes on to describe different forms of symptomatic and functional hypersomnias, such as idiopathic hypersomnia, neurotic hypersomnia, the Pickwickian syndrome" and its variants as well as different varieties of periodic long cycle hypersomnias. Finally the author makes a brief mention of the syndrome of insufficiency of wakefulness.     

系统性红斑狼疮患者血清增殖诱导配体水平的检测及其临床意义

目的:检测系统性红斑狼疮(SLE)和类风湿性关节炎(RA)患者血清中增殖诱导配体(APRIL)的水平,探讨APRIL水平与SLE患者临床指标的相关性及APRIL在SLE发病中的作用.方法:采用ELISA法检测SLE患者组(48例)、RA患者组(16例)和正常对照组(16例)血清APRIL水平,并与SLE活动指数(SLEDAI)及实验室指标进行对比分析.结果:SLE组和RA组血清APRIL水平高于正常对照组(P<0.01),SLE组高于RA组(P<0.01).SLE组中抗Sm抗体阳性患者APRIL水平高于阴性患者( P<0.05).抗U1-RNP抗体阳性患者APRIL水平高于阴性患者( P<0.05),抗SSA /SSB抗体、抗ACL抗体、抗ds-DNA抗体阳性和阴性患者APRIL水平差异无统计学意义.SLE患者血清APRIL水平与其补体C3、C4呈负相关关系(r1=-0.819,P<0.01;r2=-0.549,P<0.01),与SLEDAI评分、免疫球蛋白、抗核抗体谱等免疫学指标无相关性.结论:APRIL在SLE患者中特异性升高,可能在狼疮发病中起重要作用;血清APRIL水平可能与SLE患者疾病活动程度有关联,但尚不能确定是否可作为疾病活动性指标.     

Two cases of systemic lupus erythematosus associated with fatty liver and Basedow's disease

We present two cases of systemic lupus erythematosus (SLE) associated with both Basedow's disease and fatty liver. The first case is a 46-year-old Japanese female who was admitted because of high fever and general fatigue. She had been diagnosed as having Basedow's disease and treated with thiamazole for over 4 years. Since thiamazole-induced lupus was unlikely because of high titer anti-nuclear antibody and anti-DNA antibody and low levels of complements, a diagnosis of SLE was made. The upper abdominal ultrasound study and the specimen obtained by liver biopsy performed before initiating steroid therapy demonstrated marked fatty liver. SLE itself is considered as an etiology of fatty liver in this case. The second case was a 25-year-old Japanese female with SLE. She had been treated with prednisolone for 13 years and was complicated with Basedow's disease 10 years later. Fatty liver was also demonstrated in this patient on ultrasonography, and was thought to be resulted from long-term steroid hormone administration.     

The MOS 36-item Short-Form Health Survey (SF-36): III. Tests of data quality, scaling assumptions, and reliability across diverse patient groups

The widespread use of standardized health surveys is predicated on the largely untested assumption that scales constructed from those surveys will satisfy minimum psychometric requirements across diverse population groups. Data from the Medical Outcomes Study (MOS) were used to evaluate data completeness and quality, test scaling assumptions, and estimate internal-consistency reliability for the eight scales constructed from the MOS SF-36 Health Survey. Analyses were conducted among 3,445 patients and were replicated across 24 subgroups differing in sociodemographic characteristics, diagnosis, and disease severity. For each scale, item-completion rates were high across all groups (88% to 95%), but tended to be somewhat lower among the elderly, those with less than a high school education, and those in poverty. On average, surveys were complete enough to compute scales scores for more than 96% of the sample. Across patient groups, all scales passed tests for item-internal consistency (97% passed) and item-discriminant validity (92% passed). Reliability coefficients ranged from a low of 0.65 to a high of 0.94 across scales (median = 0.85) and varied somewhat across patient subgroups. Floor effects were negligible except for the two role disability scales. Noteworthy ceiling effects were observed for both role disability scales and the social functioning scale. These findings support the use of the SF-36 survey across the diverse populations studied and identify population groups in which use of standardized health status measures may or may not be problematic.     

Impaired phagocytosis of apoptotic cell material by monocyte-derived macrophages from patients with systemic lupus erythematosus

OBJECTIVE: To investigate whether the established impaired phagocyte function in systemic lupus erythematosus (SLE) patients also affects apoptotic cell clearance. Accumulation of apoptotic waste as a source for autoantigens that induce and maintain autoimmune responses is discussed. METHODS: Apoptosis was detected by morphology and propidium iodide staining. In vitro phagocytosis of autologous apoptotic cells in cultured peripheral blood mononuclear cells was evaluated microscopically. Cross-feeding experiments were performed to investigate phagocytosis of heterologous apoptotic cells by in vitro-differentiated macrophages. Furthermore, the effect of annexin V on the phagocytosis of apoptotic cells was investigated. RESULTS: Reduced clearance of apoptotic cells in SLE patients was observed. The defective clearance appeared to reflect phagocyte dysfunction and not an abnormal execution of apoptosis. A similar picture was seen when in vitro-differentiated macrophages from control populations were treated with annexin V. CONCLUSION: Noninflammatory engulfment phagocytosis of apoptotic cells is decreased in SLE patients. Persistently circulating apoptotic waste may encounter inflammatory removal pathways and serve as immunogen for the induction of autoreactive lymphocytes and as antigen for immune complex formation.     

Testing the validity of the Euroqol and comparing it with the SF-36 health survey questionnaire

There is an interest in the consequences of deriving a single index measure of health for validity and sensitivity. This paper presents the results of testing a recent example of a general health measure designed to derive a single index, the Euroqol (EQ), and presents a comparison with a new, influential profile measure, the Short Form 36 (SF-36) Health Survey Instrument. The EQ and an anglicised version of the SF-36 health survey, both designed for self-completion, were included in a postal survey of a random sample of 1980 patients from two practice lists in Sheffield, UK. The response rate for the EQ questionnaire was 83%, and the rate of completion over 95%. Evidence was found for the construct validity of the EQ dimension responses and the derived total EQ health score in terms of distinguishing between groups with expected health differences. Considerable agreement was found between EQ responses and the total EQ score, and the UK SF-36 profile scores. There was substantial evidence of EQ being less sensitive at the ceiling (i.e. low levels of perceived ill-health) and throughout the range of health states. A recent restructuring of the EQ, may help overcome some of the problems with the physical dimensions by reducing their skewness.     

The characteristics of kidney involvement in a female patient with systemic lupus erythematosus and the antiphospholipid syndrome

A case of rapidly progressive nephritis is reported in a female patient having systemic lupus erythematosus (SLE) with antiphospholipid syndrome. Clinical presentation of progressive lupus nephritis with intensifying renal insufficiency, arterial hypertension, hematuria, nephrotic syndrome was associated with unusual morphological manifestations of mesangiocapillary glomerulonephritis with advanced vasculitis. The authors attribute a malignant nephritis course atypical for patients with antiphospholipid syndrome to development of renal vasculitis. The discussion covers lupus genesis of vascular involvement, a probable triggering role of antibodies to phospholipids in impairment of endothelial cells.     

Alteration of T-lymphocyte subpopulations in patients with primary renal diseases and systemic lupus erythematosus

Forty-eight patients with a variety of primary renal diseases and systemic lupus erythematosus (SLE) were examined for the proportion of circulating T lymphocytes bearing receptors for IgM (T mu cells) or IgG (T gamma cells). Although the control group showed strikingly similar mean values for both T mu and T gamma cells, the whole group of patients with primary renal diseases and SLE showed a wide scatter of values. Sixteen patients with primary renal diseases and SLE had higher proportions of T gamma cells than the control group, whereas seven patients with chronic glomerulonephritis (CGN), membranoproliferative glomerulonephritis (MPGN), lipoid nephrosis (LN), and SLE showed very marked decrease in the proportions of T gamma cells in the peripheral blood. On the other hand, six out of the total group of patients had low proportions of T mu cells in the peripheral blood. However, no consistent relationship between the proportion of T mu and T gamma cells was found in our study. These findings indicate that there exists a heterogeneity of T-lymphocyte subpopulation distribution in some patients with primary renal diseases and SLE. The possible significance of these phenomena in the pathophysiology of renal diseases is discussed.