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PubMed1995

Local versus systemic immunoreactivity to collagen and the collage-like region of C1q in rheumatoid arthritis and SLE.

In this paper we discuss recent data concerning immunoreactivity on the one hand to the cartilage derived molecule type II collagen (CII) and on the other hand to the complement factor C1q, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). By using the ELISPOT method we have been able to show that production of antibodies to CII and to C1q is common in inflamed joints but not in the periphery of RA-patients, whereas production to C1q is commonly seen in the circulation of active SLE patients. Previously an immunological cross-reactivity has been described between these two proteins. The possibility of in vivo cross-reactivity between these two molecules might have consequences for the different disease manifestations in RA and SLE. This paper also stresses the importance of single cell analysis of antibody production when evaluating local antibody production in different body compartments and also when the aim is to assay changes in antibody production over time.

Animals↗

PubMed1997

Seasons of the year and activity of SLE and Behcet's disease.

Patients with systemic lupus erythematosus (SLE) were evaluated using a telephone questionnaire on the activity of various disease manifestations during the seasons of the past year. The results were compared to those of patients with Behcet's disease (BD), using the same questionnaires, and analyzed in relation to the mean temperature, humidity, barometric pressure, and ultraviolet radiation (UVR) in the patient's location, obtained from the official Israeli Meteorological Service. It was found that SLE patients had a tendency towards winter worsening of clinical manifestations, shown as increased incidence of joint pains, weakness, fatigue, Raynaud's phenomenon, and rash, as well as increased number of hospital admissions, sick leaves, and need to raise the dose of medications. The symptoms of patients with BD were not correlated to seasons of the year, except for increased joint pains in autumn and spring. We suggest that UVR accumulation might cause exacerbations in SLE patients several months after prolonged exposure to sunlight in the summer.

Adult↗

PubMed1992

MHC gene products and anticardiolipin antibodies in systemic lupus erythematosus results of a multicenter study. SLE Study Group.

Anticardiolipin antibodies (aCL) and HLA-DR antigens were determined in 314 central European patients with systemic lupus erythematosus (SLE). Both HLA-DR4 and DR7 were increased in aCL-positive patients, and aCL were significantly associated with DRw53. The association between DRw53 and aCL was also apparent in those 17 patients with SLE and the anticardiolipin syndrome. There was no association between aCL and HLA-DQ or C4 alleles in SLE.

Antibodies, Anticardiolipin↗

PubMed1992

Elevated gene expression of argininosuccinate synthetase in peripheral lymphocytes from systemic lupus erythematosus (SLE) patients.

Argininosuccinate synthetase (ASS) is a rate-limiting enzyme of urea cycle and functions primarily in the liver, whereas ASS activity is hardly detected in normal lymphocytes. In this study, we examined the level of ASS gene expression in peripheral blood lymphocytes (PBL) from human SLE patients by amplification of reverse-transcribed mRNA using the polymerase chain reaction. We have demonstrated that (a) approximately 40% of SLE patients exhibited 2.5 to 5 times higher expression of ASS gene in PBL than those of healthy PBL and (b) the elevation of ASS gene expression of PBL significantly correlates with the active pathogenesis of SLE patients according to the criteria of Japanese Ministry of Health and Welfare (p < 0.001 by student's two-tailed t-test). Thus, it is suggested that ASS gene expression is a promising marker of hyperactivated lymphocytes uniquely generated in patients with systemic autoimmune disease.

Animals↗

PubMed1992

Spectrotypes of anti-DNA antibodies show that anti-DNA-secreting B-cell clones of SLE patients are restricted in number, stable and long lived.

We have investigated the number of B-lymphocyte clones secreting anti-ssDNA antibodies in SLE patients and a chronic active hepatitis patient by isoelectric focusing and reverse immunoblotting of serum antibodies. Individual clones can be identified by the unique pattern of bands produced by their antibodies (the clonotype). Using this technique, we have shown that the anti-DNA response of the majority of SLE patients is clonally restricted, in many cases only a single B-cell clone responding. We have also measured qualitative and quantitative changes in expression of B-cell clones and shown that these clones are remarkably stable with lifespans of up to six years or more. These results are in agreement with previous observations of clonal restriction of the anti-DNA response in three mouse models of SLE and in addition show that, unlike the mouse models, human anti-DNA-secreting B-cell clones are extremely stable and long-lived. The implications of these results for models of initiation and regulation of the autoimmune response are discussed.

Antibodies, Antinuclear↗

PubMed1994

Inhibition of autoantibody production in experimental SLE by pre-immunization with DNA.

Experimental SLE can be induced in susceptible mice by their immunization with the human monoclonal anti-DNA antibody that bears a major idiotype-16/6 Id. The SLE afflicted mice produce a variety of autoantibodies including anti-DNA antibodies. It was of interest to find out the effect of DNA on the induction of the experimental disease. To this end, mice were immunized with combinations of 16/6 Id and DNA. The results indicated that whereas mice primed with 16/6 Id developed high titers of antibodies to the 16/6 Id and a variety of autoantibodies typical to the experimental SLE, preimmunization of mice with ssDNA led to a reduction in the 16/6 Id specific antibodies and in the autoantibody titers. No significant differences could be detected in the clinical manifestations which are present in the mice with experimental disease (increased erythrocyte sedimentation rate, leukopenia, proteinuria and glomerular immune complex deposition) in all mice immunized with 16/6 Id including those pretreated with DNA. Thus, no direct correlation exists between the autoantibody levels and the clinical pathology, and probably other factors are involved in the development of the experimental disease.

Animals↗

PubMed1999

[A case of elderly-onset systemic lupus erythematosus (SLE) complicated with severe liver dysfunction and pancytopenia due to myelofibrosis].

A 67-year-old woman was admitted to our hospital with a fever. She had been experiencing arthralgia for about one month. On admission, she had a fever of 38.5 degrees C, was anemic and was experiencing tenderness in the joints of both hands, elbows and feet. Laboratory data revealed proteinuria, urinary cylinders, pancytopenia (WBC 900/mm3, Hb 9.5 g/dl, Plt 7.8 x 10(4)/mm3), liver dysfunction (GOT 414 IU/l, GPT 140 IU/l), and hyper-gamma globulinemia. Antibiotics and granulocyte-colony stimulating factor were administered intravenously. Bone marrow aspiration was unsuccessful, but a bone marrow biopsy revealed bone marrow fibrosis. Immunological examinations were positive for antinuclear antibodies, anti-deoxyribonucleic acid (DNA) antibodies, anti-double stranded anti- DNA antibodies, as well as a decreased level of serum complement and an increased level of serum immune complexes. Tests for viral antigens and antibodies known to cause hepatitis were negative. Based on these findings, a diagnosis of SLE accompanied by liver dysfunction and bone marrow fibrosis was made. Steroid pulse therapy was initiated, but her liver function deteriorated on the first day of steroid therapy, and she died three days later. SLE accompanied by myelofibrosis is extremely rare, and only 17 and cases have been reported to date. Among these reports, the present case is the second oldest subject and the first SLE patient to suffer from both myelofibrosis and severe liver dysfunction.

Aged↗

PubMedDate not supplied

[Chronic inflammation and endothelial dysfunction: analysis of a cohort of patients with SLE and UCTD].

OBJECTIVE: Cardiovascular complications, mainly caused by an accelerated atherosclerosis, are one of the leading causes of death and disability in patients with systemic autoimmune diseases. Endothelial dysfunction is considered the earliest and reversible step of atherogenesis. Aim of the present study is to investigate endothelial function (EF) in patients with systemic lupus erythematosus (SLE), undifferentiated connective tissue diseases (UCTD) and correlate the results with clinical and laboratory variables. METHODS: EF was assessed on the peripheral microcirculation by the perfused forearm technique that can estimate both endothelium- dependent and endothelium- independent vasodilatation. The same evaluation has been repeated in two patients after the administration of 20 mg of 6-metilprednisolone. RESULTS: Twenty-three female patients with SLE or UCTD, with a follow up of at least 1 year have been studied and compared with 8 healthy controls matched for epidemiological variables and traditional risk factors for cardiovascular disease. A significant reduction both in endothelium dependent than endothelium independent vasodilatation was observed in both patients groups compared with controls. In addition, UCTD patients demonstrated a significant reduction in the nitric oxide pathway compared with controls and SLE patients. Finally, steroid administration induced an improvement of vascular reactivity. CONCLUSIONS: Despite the well documented side effects of chronic corticosteroid therapy, our data might suggest a role for antinflammatory and immunosuppressive therapy in the prevention of premature atherosclerosis in patients with systemic autoimmune diseases.

Adult↗

PubMed1975

Effects of lymphocytotoxins of systemic lupus erythematosus (SLE) sera on T and B lymphocytes.

SLE lymphocytotoxins can be demonstrated on the lymphocytes by immunofluorescence. Complement addition lyses the cells covered with LCT. The proportion of B and T cells as determined by surface immunoglobulins and spontaneous rosette formation of lymphocytes from healthy donors remains unchanged after LCT and complement treatment. The proportion of B and T cells of SLE lymphocytes was altered after cell lysis. The B cells seemed to be relatively resistant, and the T cells more susceptible, to autologous LCT. Thus the relative decrease in the number of T cells in active SLE may be the consequence of surface bound LCT with its effect on the circulating T cells.

B-Lymphocytes↗

PubMed2000

Correlation among WHO classes, histomorphologic patterns of glomerulonephritis and glomerular immune deposits in SLE.

In addition to the conventional World Health Organization (WHO) classification of lupus glomerulonephritis (GN), various concomitant approaches have been introduced in the evaluation of renal biopsies of patients with systemic lupus erythematosus (SLE) in order to increase the impact of biopsies on the decision concerning the most appropriate therapy as well as for establishing the prognosis. Three hundred and seventy kidney tissue samples from 267 SLE patients were analysed using standardised light, electron and immunofluorescence microscopic techniques. In 155 patients, a comparative clinical follow-up study and statistical analysis were performed. The study highlighted the heterogeneity of WHO classes IV and III, which include 5 and 6 different conventional histomorphologic types of GN, respectively. Mixed membranous and proliferative GN associated with "full-house" mesangial-transmembranous immune deposits, demonstrated in more than one third of our SLE cases, appears to be diagnostically most characteristic. Immune deposits distributed in the glomeruli in five different patterns, obviously play a major role in the pathogenesis of various WHO classes and histomorphologic types of lupus GN. Additional mechanisms related to the occurrence of antiphospholipid antibodies and antineutrophil cytoplasmic antibodies are suggested to contribute to the histomorphologic heterogeneity of WHO class III and IV lupus GN, particularly to the development of thrombotic, necrotising and crescentic glomerular lesions. In the present study, a statistically significant association was demonstrated between increasing mean values of the activity index and glomerular deposit distribution patterns labeled by subendothelial deposits. Furthermore, a significant correlation was established between an increasing risk of developing renal failure and increasing mean values of the chronicity index. Differences in the increasing risk of developing renal failure between groups with different histomorphologic types of GN and different immune deposit distribution patterns were not statistically significant. The surprisingly high renal survival rate of more than 80% noted in lupus patients with predominantly necrotising crescentic GN during the mean follow-up period of 40 months appears to be related to the more aggressive treatment of those patients. Our study confirmed a significant role of the WHO classification of lupus GN in the decision concerning the most appropriate treatment and prognostication. An increasing risk of irreversible renal failure in patients with WHO class IV lesions in contrast to those of WHO class III and in contrast to those of the category incorporating all other WHO classes was shown to be statistically significant.

Adolescent↗

PubMed1992

Circulating immune complex levels measured by new ELISA kits utilizing monoclonal anti-C1q and anti-C3d antibodies correlate with clinical activities of SLE but not with those of RA.

The authors studied sera from both patients with SLE and from those with RA to evaluate clinical usefulness and significance of circulating immune complexes (CIC) detected with new ELISA kits utilizing monoclonal anti-C1q and anti-C3d antibodies. CIC values of patients with SLE significantly correlated to severity of disease activities evaluated by clinical symptoms and laboratory tests, especially for serum complement levels. Since substances detected with the ELISA kits were closely related to serum complement components, it was determined that a direct relationship exists between clinical activities and CIC values appearing in SLE patients with hypocomplementemia. In RA patients, CIC values did not correlate to clinical activities evaluated by Lansbury's index, anatomical bone damage with X-ray or functional assessment of activities of daily living, but did significantly correlate to levels of IgM-RF, serum IgG concentrations and some markers of systemic inflammation. Detection of IC after fractionation of RA sera revealed a broad range of molecular sizes detectable with the ELISA kits, which indicated that CIC in vivo were heterogenic and complicated in formation, degradation and interaction with serum complements.

Adult↗

PubMed1992

[Tubulo-interstitial nephritis (TIN) with no glomerular lesions, distal renal tubular acidosis and asteatosis cutis in a patient with systemic lupus erythematosus (SLE): a case report].

We report a 28-year-old woman with systemic lupus erythematosus (SLE) who showed tubulo-interstitial nephritis (TIN) without any glomerular changes. In 1990, she was admitted to our hospital, complaining of anorexia, vomiting and persistent high fever. Laboratory findings showed proteinuria, pancytopenia, hypocomplementemia and positive for antinuclear antibody, anti-DNA antibody, anti-Sm antibody, anti-SSA antibody and anti-SSB antibody. We made a diagnosis of SLE. Furthermore, distal renal tubular acidosis and asteatosis cutis were revealed. The diagnosis of Sjögren's syndrome was not made. We treated with high-dose prednisolone (60mg/day) and achieved improvement of symptoms and laboratory data. Open renal biopsy showed TIN without any glomerular changes. Predominant TIN is very rare in SLE. We discussed its pathogenesis and relation to the renal lesions of Sjögren's syndrome.

Acidosis, Renal Tubular↗

PubMedDate not supplied

Disease activity in systemic lupus erythematosus: report of the Consensus Study Group of the European Workshop for Rheumatology Research. II. Identification of the variables indicative of disease activity and their use in the development of an activity score. The European Consensus Study Group for Disease Activity in SLE.

A European Consensus Group study, involving 29 centres from 14 countries, was performed in order to reach agreement on the definition of disease activity in systemic lupus erythematosus (SLE) and to construct a new disease index. Data on 704 lupus patients were collected and analysed, using univariate and multivariate statistical procedures, to select those clinical and laboratory features of the disorder which best correlate with the global assessment of disease activity assigned to the patients by the physician of each participating centre. A combination of 15 clinical and laboratory variables was shown to be the best predictor of disease activity in SLE. A European Consensus Lupus Activity Measurement (ECLAM) was then formulated. This index included the 15 selected variables, weighted (with some adjustments) according to their respective regression coefficients in the multivariate model. ECLAM appears to be an effective instrument for scoring patients with different degrees of disease activity. This is the first SLE disease activity index based on data from a very large number of lupus patients followed at a large number of lupus centres in different countries. It might therefore very well serve as a standardised measure for future European clinical studies. Final assessment of the validity, reliability and sensitivity of this index is now underway.

Europe↗

PubMedDate not supplied

Possible role of DNA hypomethylation in the induction of SLE: relationship to the transcription of human endogenous retroviruses.

OBJECTIVE: We investigated the contribution of DNA methyltransferase activity to the transcription of human endogenous retroviruses (HERV), which have been reported to be a plausible causative agent for systemic lupus erythematosus (SLE). METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) and real-time quantitative-PCR (RQ-PCR) were used. RESULTS: Our results indicated that treatment with 5-aza-deoxycytidine (5-aza C), a demethylating agent, increased the transcription of messenger RNA (mRNA) for HERV clone 4-1 and decreased mRNA for DNA methyltransferase-1 (DNMT-1; methylation-regulating enzyme) in peripheral blood mononuclear cells (PBMC) from normal individuals. Also, transcription of DNMT-1 mRNA in PBMC from patients with SLE was lower than in cells from normal controls. CONCLUSION: DNA hypomethylation seems to play a significant role in the transcription of HERV clone 4-1 and may be related to the pathogenesis of SLE.

Adult↗

PubMed2003

[Application of CD34+ autologous peripheral progenitor cell transplant in the treatment of children with refractory SLE].

OBJECTIVE: Systematic lupus erythematosis (SLE) is a severe disease which affects the patient for many years and there is no radical cure for the disease. To explore a possible way to treat children with refractory SLE, the authors treated 2 children with grade III and IV lupus nephropathy for 5 years and 7 years respectively, mainly presented with persistent thrombocytopenia, proteinuria, pleural effusion with CD34(+) autologous peripheral progenitor cells transplantation. METHODS: Mobilized with G-CSF and collected with CS-3000 Cell Separator, passed through the CliniMacs CD34(+) cell selection device, the count of CD34(+) cells obtained reached 1.0 x 10(6)/kg and 1.7 x 10(6)/kg, respectively with the remaining of 2.0 x 10(5)/kg and 1.0 x 10(4)/kg of CD3(+) cells individually. The selected CD34(+) cells were frozen at -80 degrees C. The conditioning regimen consisted of cyclophosphamide [50 mg/(kg x day) for 4 days] plus ATG [Fresennius S 5 mg/(kg x day) for 3 days]. After 48 h treatment with cyclophosphamide, the frozen stem cells were infused back to the patients. RESULTS: Neutrophils recovered on 9 and 7 days after transplantation respectively in these 2 cases. Beginning from 15 days, the platelet count recovered and remained at over 100 x 10(9)/L. The sign of Cushing's syndrome disappeared completely 3 months after transplantation because discontinuing the steroid. One child's height had a 5 cm increase within 6 months after stopping steroid and this was the first height gain during the 7 years since she had had the disease. Till this paper was written, these 2 children were followed up for 13 months and 6 months, respectively, all the original symptoms and autoantibodies related to autoimmune disorders disappeared. But the cell-mediated immunity did not recover yet with the CD4(+) cell level still remained at a lower level. CONCLUSION: The effect of CD34(+) autologous peripheral progenitor cell transplantation on the children with refractory SLE was satisfactory so far, but the long-term effect remains to be confirmed by further studies on more cases.

Adolescent↗

PubMed1992

Pathogenic aspects of systemic lupus erythematosus (SLE).

Antibodies against native DNA are a disease-specific marker for systemic lupus erythematosus (SLE) and in addition, there is direct evidence that these antibodies also play a major part in pathogenic mechanisms leading to systemic and organ-specific disease manifestations. The origin of anti-dsDNA antibodies is still poorly understood, especially as dsDNA per se is not immunogenic. As recently shown, evidence is now accumulating that anti-dsDNA antibodies are most likely germline-encoded and antigen-selected, as demonstrated by sequence analysis of human anti-dsDNA antibody clones from SLE patients. With regard to the possible autoantigen it is of interest that sera of SLE patients show an elevated level of nucleic acids, which at least can partly be explained by defective clearance mechanisms. The question, however, whether these nucleic acids could serve as an autoantigen triggering off anti-dsDNA antibodies has not yet been solved.

Antibodies, Anti-Idiotypic↗

PubMed2004

The autoantibody profile and its association with clinical manifestations in Malay SLE patients.

A cross sectional study was conducted to determine the auto-antibody profile of Malay SLE patients in Kelantan, North East Malaysia and to correlate them with clinical presentations. Eighty-two Malay SLE patients who fulfilled the ARA criteria underwent the following tests: ANA, anti-dsDNA antibody, anti-ENA antibody and RF. The results revealed that ANA was positive in 91.5% of the patients, anti-dsDNA antibody in 53.7%, however, anti-ENA antibodies were positive in only 9.8% of the cases at the time of the study and none had a positive RF. The profile of autoantibodies was similar to other studies except for a lower incidence of anti-ENA antibodies. Sixty three percent of patients had lupus nephritis. The pattern of clinical presentations were noted to be more similar to those found among Chinese and Indian SLE populations than compared to the Caucasians. There was a significant association between anti-dsDNA antibody and lupus nephritis and between anti-ENA antibody and thrombocytopenia.

Adolescent↗

PubMed2005

Chorea and microphonia as presenting feature of SLE.

Systemic lupus erythematosus (SLE) is a multisystem immunologic disease. Renal and neurological manifestations are frequently seen in childhood SLE. Out of the neurological features movement disorders are uncommon. A case of SLE is presented here with unusual neurological manifestation i.e. chorea associated with microphonia.

Child↗