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PubMed1990

[Role of T lymphocytes in systemic lupus erythematosus].

In very active systemic lupus erythematosus (SLE), the serum levels of interleukin-2 (IL-2) are increased, indicating activation of T lymphocytes in the organism. The peripheral blood, however, contains T cells with a strongly reduced functional capacity, which results from a post-activation/refractory state; this hypofunction is reversible. Thus, the activity of the T lymphocytes in the circulating pool is the "mirror image" of the activity of these cells at the level of the whole organism. The B lymphocyte hyperactivity in SLE is T-dependent. A highly specific mechanism is involved in the activation of the B cells producing anti-native DNA antibodies. The investigation of lymphocyte functions enables one to follow the effect of immunosuppressive therapy.

B-Lymphocytes↗
PubMed2004

Genetics of human systemic lupus erythematosus: the emerging picture.

Systemic lupus erythematosus (SLE) is a systemic autoimmune inflammatory disease with partially understood etiology, which can affect virtually any organ. Despite suggestions to the contrary, SLE is proving to be a reliable phenotype for genetic studies. Similar to many other autoimmune diseases, SLE demonstrates a complex pattern of inheritance that is consistent with the involvement of multiple susceptibility genes as well as environmental risk factors. During the past several years, some new candidate genes have been implicated in induction of SLE through association studies, and multiple susceptibility regions have been detected through genome-wide linkage studies. Many of the susceptibility effects have been confirmed by independent studies.

Antigens, CD↗
PubMed1996

[Relationship between higher cortical dysfunction and the findings of magnetic resonance imaging in systemic lupus erythematosus].

The relationship between systemic lupus erythematosus (SLE) and organic lesions was investigated by magnetic resonance imaging (MRI) to clarify the etiology of higher cortical dysfunction in SLE. The subjects were 10 patients with SLE, and higher cortical dysfunction was observed in 8 (80%) of the 10 patients. 5 (82.5%) of the 8 patients showed abnormal MRI findings. The findings of higher cortical dysfunction were consistent with the MRI findings in 1 of the 5 patients, but not in the remaining four. MRI revealed no lesion despite the presence of higher cortical dysfunction in three patients. These results suggest that the association of organic changes and functional changes in cerebral nerve cells is important in etiology of higher cortical dysfunction in SLE.

Adult↗
PubMed1996

Herpes zoster myelitis occurring during treatment for systemic lupus erythematosus.

A woman with systemic lupus erythematosus (SLE) presented with a zoster eruption. Transverse myelitis developed at the site of the dermatomal distribution of the rash. SLE and varicella zoster virus (VZV) can both cause myelitis, and are difficult to differentiate. The topographic association between the cutaneous and the neurological involvement suggesting VZV myelitis was confirmed by polymerase chain reaction (PCR) for VZV in the cerebrospinal fluid. This case illustrates the potential role of the selective amplification of VZV DNA in cerebrospinal fluid to diagnose central neurological complications associated with VZV. The value of magnetic resonance imaging of the spinal cord in the evaluation of patients with myelitis is emphasized.

DNA, Viral↗
PubMed1996

SLICC/ACR Damage Index is valid, and renal and pulmonary organ scores are predictors of severe outcome in patients with systemic lupus erythematosus.

We investigated the Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index as a predictor of severe outcome and an indicator of morbidity in different ethnic groups, and in regard to its validity. We retrospectively studied disease course within 10 yr of diagnosis in an inception cohort of 80 patients with systemic lupus erythematosus (SLE). The mean renal damage score (DS) at 1 yr after diagnosis was a significant predictor of endstage renal failure and the mean pulmonary DS at 1 yr significantly predicted death within 10 yr of diagnosis. Compared to Caucasians, Afro-Caribbeans and Asians had significantly higher mean total DS at 5 and 10 yr, and higher mean renal DS at 10 yr. At 5 yr, the mean renal DS in Afro-Caribbeans and the mean neuropsychiatric DS in Asians were significantly higher than in Caucasians. The rate of endstage renal failure in Caucasians was significantly lower than in the other ethnic groups. Our results confirm the validity of the SLICC/ACR Damage Index.

Adult↗
PubMed1991

Acute cerebrovascular episodes in systemic lupus erythematosus.

Twelve patients with systemic lupus erythematosus (SLE) who developed major acute cerebrovascular episodes are described. All patients were female, with a mean age of 43.3 years and they had suffered from SLE for between 1 month and 22 years (mean 9.3 years) at the time of stroke. All patients had multiple clinical and laboratory features of systemically active SLE. Stroke was the initial neurological feature in nine patients. Cerebral infarction was confirmed in eight patients and cerebral haemorrhage in two; the two remaining patients had convincing clinical evidence of thromboembolic neurological complications. Characteristic clinical and serological features of antiphospholipid antibodies were observed in six patients (50 per cent). Five patients died as a direct result of stroke and two other patients died within one year.

Acute Disease↗
PubMed1979

HLA-linked C2 deficiency in a Dutch patient with systemic lupus erythematosus.

A patient with systemic lupus erythematosus was studied whose blood serum on repeated occasions showed undetectable levels of haemolytic omplement (C). A detailed investigation of individual C components in the serum of the proposita and her family revealed the absence of functional C2 in the patient and half-normal values in the relatives. C4 levels in the family, but not in the patient, were above normal, whereas the levels of factor B were low in all cases. No abnormalities were noted in C3, C9, or C1INH. Tissue typing showed linkage of the C2-deficiency gene with the HLA-A10/B18 and A9/B18 haplotypes. No linkage with red cell antigens and no relationship with plasma kallikrein levels was found.

Adolescent↗
PubMed1991

Thyroid-gonad relationship in systemic lupus erythematosus.

Thirty women with systemic lupus erythematosus (SLE) were examined to assess the thyroid-gonad relationship. Significant decreases in mean serum tri-iodo-thyronine and testosterone levels and increases in mean serum estradiol and luteinizing hormone levels were observed in SLE patients as compared to control subjects. The serum levels of thyroxine, thyrotropin, tri-iodo-thyronine uptake, free thyroxine index and prolactin were, however, not significantly different in both groups. The interpretation of these findings is unclear but SLE could be regarded as one of the nonthyroidal systemic illness since low serum tri-iodo-thyronine with normal thyrotropin levels were observed in our patients. Furthermore, high levels of estradiol and low levels of testosterone in our female patients may indicate involvement of sex steroids in the pathogenesis of SLE.

Adolescent↗
PubMed2001

[Expression of Fas and Fas ligand in lesions of patients with discoid lupus erythematosus].

OBJECTIVE: To study the relation of apoptosis and pathogenesis of lupus erythematosus. METHODS: Expressions of Fas and Fas ligand(FasL) were detected in 30 lesions of discoid lupus erythematosus(DLE) and 5 skin specimens from healthy controls by immunohistochemical staining. RESULTS: Fas and FasL were positively expressed in most epidermal keratinocytes, infiltrating lymphocytes around blood vessels and appendages, and Fas was positively expressed in a few sweat ducts and hair follicles. Fas and FasL expressions were weakly positive or negative in healthy controls. CONCLUSION: Apoptosis induced by Fas, FasL pathway may be related to the pathogenesis of lupus erythematosus.

Adult↗
PubMed2007

Autoimmune hepatitis with raised alpha-fetoprotein level as the presenting symptoms of systemic lupus erythematosus: a case report.

Systemic lupus erythematosus (SLE) and autoimmune hepatitis are distinct clinical disorders, which rarely occur, in the same patient. We describe a 59-year-old woman with coexistence of both conditions. Photosensitivity, arthritis, positive ANA, and extreme elevation of anti-dsDNA concluded the diagnosis of SLE. Hyperbilirubinemia, high serum value of liver function, and elevation of alpha-fetoprotein were also prominent. By a review of pertinent literature, clinical investigation, calculation of autoimmune hepatitis score, and pathology of liver biopsy specimen, we were in favor of autoimmune hepatitis. Awareness of this rare presentation may be beneficial to clinicians in identifying and treating patients with both SLE and autoimmune hepatitis.

Diagnosis, Differential↗
PubMed1988

Anti-histone antibodies (ELISA and immunoblot) in canine lupus erythematosus.

In the canine systemic lupus erythematosus (SLE), anti-double stranded DNA (ds-DNA) antibodies (enzyme linked immunosorbent assay (ELISA) or indirect immunofluorescence on Crithidia luciliae) are rare whereas anti-histone antibodies are often found: 61.7% with ELISA and 74% with immunoblot. In canine SLE the pattern of anti-histone antibodies on immunoblot is different from anti-histone antibodies in human SLE. Indeed, histone fractions which are most often recognized by the canine antibodies are by order of frequency H3, H4 and H2A, whereas in man this order is H1, H2B then H3. In the diagnostic criteria of canine SLE, we suggest replacing the anti-ds-DNA antibodies by the anti-histone antibodies detected by immunoblot.

Animals↗
PubMed1993

Warts and lupus erythematosus.

The human papilloma virus is implicated in causing several diseases, ranging from the common wart to malignancy. We describe a high prevalence of cutaneous warts in lupus erythematosus. The presence of warts did not correlate with the taking of immunosuppressive drugs. This observation suggests that there is a primary immunological defect among patients with lupus erythematosus. We found this high rate among patients with discoid as well as systemic lupus erythematosus. We found no correlation between the prevalence of cutaneous warts and cervical dysplasia, or malignancy. Discoid lupus erythematosus is often considered to be a different disease from systemic lupus erythematosus, running a more benign course. The high prevalence of cutaneous warts in both conditions highlights yet another similarity between these two diseases.

Adolescent↗
PubMed1993

Interleukin-3 immunoassay in systemic lupus erythematosus patients: preliminary data.

Systemic lupus erythematosus (SLE) may be associated with thrombocytopenia on one hand and lymphoma on the other. Interleukin-3 (IL-3) may contribute to both conditions. IL-3 is a pleotrophic growth factor affecting the proliferation and differentiation of stem cells to committed progenitors of several hematopoietic lineages including megakaryocytes and lymphocytes. The serum level of IL-3 determined by ELISA was found to be higher in a cohort of 16 patients with SLE in comparison to health controls. The IL-3 levels were highest in 2 patients with SLE and lymphoma. Interestingly, low serum levels were detected in SLE patients with thrombocytopenia. Our preliminary results may point to the role of IL-3 in the hematopoietic changes observed in SLE.

Enzyme-Linked Immunosorbent Assay↗
PubMed1990

Systemic lupus erythematosus in a filly.

Systemic lupus erythematosus (SLE) was diagnosed in a 2-year-old Standardbred filly. Clinical signs of SLE included weight loss, bilateral symmetric alopecia, seborrhea, oral ulceration, and lymphadenopathy. Abnormal laboratory findings included a Coombs test-positive hemolytic anemia and positive antinuclear antibody test result. Histologic evaluation of multiple skin biopsy specimens revealed interface dermatitis with linear deposition of IgG at the basement membrane zones of the epidermis and hair follicles. The filly did not respond to glucocorticoid treatment and was euthanatized. Necropsy findings included membranous glomerulonephritis and fibrous synovitis. On the basis of these findings, SLE should be considered in the differential diagnosis of immune-mediated skin disease in horses. Definitive diagnosis of SLE relies on recognition of multisystemic disease and confirmatory histopathologic and immunopathologic findings.

Animals↗
PubMed1996

Heart rate variability in patients with systemic lupus erythematosus.

As patients with systemic lupus erythematosus (SLE) survive their episodes of disease activity, increasing morbidity is shown to be related to chronic cardiovascular complications. The objective of this study was to assess the cardiac parasympathetic autonomic functional status, as reflected by heart rate variability, in SLE patients with and without corticosteroid treatment. A cross-sectional study of SLE patients attending the Arthritis Clinic was done, using age and gender-matched controls. Thirty-four female patients, age 39 +/- 11, were entered, 20 of whom were receiving steroids at the time of study. Time and frequency domain heart rate variability indices were significantly reduced in the SLE groups with and without corticosteroid therapy, as compared to controls. The indices were not, however, significantly different in the two SLE groups.

Adrenal Cortex Hormones↗
PubMed2003

[Systemic treatment of cutaneous lupus erythematosus].

The treatment of cutaneous lupus erythematosus (CLE) remains a therapeutic challenge. In many cases, systemic treatment of the disease is necessary, especially in cases resistant to topical treatment or with internal organ involvement. Even though many different agents can be employed in this situation, most are not approved in Germany for the treatment of CLE. We give an overview of the agents used in the systemic treatment of CLE and review their mechanisms of action, indications and their practical use in cutaneous LE based on literature results and our own experience. We discuss corticosteroids, antimalarials, dapsone, azathioprine, cyclophosphamide, methotrexate, retinoids, cyclosporine A, mycophenolate mofetil, sulfasalazine, thalidomide, clofazimine, tacrolimus, immunoglobulins, monoclonal antibodies, plasmapheresis, etanercept, infliximab, feflunomid, gold and interferon-alpha.

Acute Disease↗
PubMed1979

Deposition of antibodies to a soluble cytoplasmic antigen in the kidneys of patients with systemic lupus erythematosus.

Two patients with systemic lupus erythematosus were studied whose sera contained precipitating antibodies to a soluble cytoplasmic antigen, termed Ro. A reduction in the amount of these antibodies in each case was accompanied by a deterioration in the clinical status with the development of nephritis leading to death. Acid elution of gamma globulin was performed from homogenates of the renal cortex, and in both instances antibodies to Ro were demonstrated in the eluates by double immunodiffusion. The titer of these antibodies was measured in both sera and eluates, and specific enrichment of anti-Ro in the eluates was demonstrated in both patients. This strongly suggests the direct participation of Ro-anti-Ro immune complexes in the progressive renal disease and may underlie the association seen here between the decreasing serum titers of antibodies to Ro and the clinical deterioration in these two cases.

Antibody Specificity↗
PubMed2006

Nonmyeloablative hematopoietic stem cell transplantation for systemic lupus erythematosus.

CONTEXT: Manifestations of systemic lupus erythematosus (SLE) may in most patients be ameliorated with medications that suppress the immune system. Nevertheless, there remains a subset of SLE patients for whom current strategies are insufficient to control disease. OBJECTIVE: To assess the safety of intense immunosuppression and autologous hematopoietic stem cell support in patients with severe and treatment-refractory SLE. DESIGN, SETTING, AND PARTICIPANTS: A single-arm trial of 50 patients with SLE refractory to standard immunosuppressive therapies and either organ- or life-threatening visceral involvement. Patients were enrolled from April 1997 through January 2005 in an autologous nonmyeloablative hematopoietic stem cell transplantation (HSCT) study at a single US medical center. INTERVENTIONS: Peripheral blood stem cells were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (5 microg/kg per day), enriched ex vivo by CD34+ immunoselection, cryopreserved, and reinfused after treatment with cyclophosphamide (200 mg/kg) and equine antithymocyte globulin (90 mg/kg). MAIN OUTCOME MEASURES: The primary end point was survival, both overall and disease-free. Secondary end points included SLE Disease Activity Index (SLEDAI), serology (antinuclear antibody [ANA] and anti-double-stranded (ds) DNA), complement C3 and C4, and changes in renal and pulmonary organ function assessed before treatment and at 6 months, 12 months, and then yearly for 5 years. RESULTS: Fifty patients were enrolled and underwent stem cell mobilization. Two patients died after mobilization, one from disseminated mucormycosis and another from active lupus after postponing the transplantation for 4 months. Forty-eight patients underwent nonmyeloablative HSCT. Treatment-related mortality was 2% (1/50). By intention to treat, treatment-related mortality was 4% (2/50). With a mean follow-up of 29 months (range, 6 months to 7.5 years) for patients undergoing HSCT, overall 5-year survival was 84%, and probability of disease-free survival at 5 years following HSCT was 50%. Secondary analysis demonstrated stabilization of renal function and significant improvement in SLEDAI score, ANA, anti-ds DNA, complement, and carbon monoxide diffusion lung capacity adjusted for hemoglobin. CONCLUSIONS: In treatment-refractory SLE, autologous nonmyeloablative HSCT results in amelioration of disease activity, improvement in serologic markers, and either stabilization or reversal of organ dysfunction. These data are nonrandomized and thus preliminary, providing the foundation and justification for a definitive randomized trial. Clinical Trial Registration ClinicalTrials.gov Identifier: NCT00271934.

Adult↗