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PubMed1991

Autoantibodies against the multicatalytic proteinase in patients with systemic lupus erythematosus.

Sera from patients with systemic lupus erythematosus contain specific autoantibodies directed against different polypeptide components of the multicatalytic proteinase (also known as proteasome or prosome). These human autoantibodies, in contrast to polyclonal antibodies obtained in rabbits against the purified enzyme, recognize highly conserved epitopes of the multicatalytic proteinase polypeptides from yeast to human.

Animals↗
PubMed1992

Molecular aspects of systemic lupus erythematosus: murine endogenous retroviral expression.

Systemic lupus erythematosus is an immune-mediated disease in which the etiology is unknown. Full-length (8.4 kb), type C, modified polytropic (Mpmv) retroviral transcripts from the thymus are characteristic of murine lupus. Reciprocal bone marrow transplantation studies determined that this thymic expression maps to the pre-T bone marrow stem cell. In vitro and in vivo oligonucleotide antisense work suggest that type C retroviruses play a role in immune activation. This paper summarizes our studies of endogenous retroviruses in murine lupus.

Animals↗
PubMed1993

Pregnancy outcome and anti-cardiolipin antibody in women with systemic lupus erythematosus.

Pregnancies in women with systemic lupus erythematosus are recognized to result in excessive fetal morbidity and mortality. Maternal autoantibody status may explain some of these problems. Anti-cardiolipin antibody has been associated with recurrent pregnancy losses in some women with lupus, but the risk of these losses has not been defined. At the University of Pittsburgh between January 1, 1979, and December 31, 1989, an unmatched case-control study design was used to determine whether patients with lupus and anti-cardiolipin antibody (81 cases) were at increased risk for adverse pregnancy outcomes in comparison with lupus patients without the antibody (174 controls). Cases had 98 of 192 (51%) pregnancies with an adverse outcome, while controls had 212 of 494 (43%). The odds ratio for having any adverse pregnancy outcome was 1.40 (95% confidence interval (CI) 0.98-1.98). When pregnancies were classified according to specific adverse outcome types, the frequency of late miscarriages (14-20 weeks gestation) in cases and controls was 8% and 3%, respectively. The odds ratio for late miscarriage was 2.94 (95% CI 1.31-6.60). When pregnancies were stratified by birth number and by occurrence of pregnancy before or after diagnosis, the increased frequency of late miscarriages in cases was noted only in the first pregnancy when the pregnancy occurred before recognized disease. Preterm births (before 38 weeks gestation) were increased in cases compared with controls in pregnancies that occurred after diagnosis for second and third pregnancies. If a case had one previous adverse outcome, the odds ratio for another adverse outcome was 3.00 (95% CI 1.62-5.57). If a case had two previous adverse outcomes, the odds ratio for a third adverse pregnancy outcome was 4.14 (95% CI 1.62-10.58). Thus, a previous adverse pregnancy outcome was the most important risk factor for an adverse outcome in a subsequent pregnancy.

Adult↗
PubMed1999

Haematopoietic stem cell transplantation for active systemic lupus erythematosus.

OBJECTIVE: For patients with systemic lupus erythematosus (SLE) who are at risk of disease-related mortality, we have initiated a protocol of intensive immunosuppression and haematopoietic stem cell support. The first patient enrolled in this study was in the midst of a lupus flare manifest by nephritis and rapidly declining renal function, uncontrolled hypertension, immune-mediated cytopenias, and serositis characterized by a large pericardial effusion and abdominal pain. Antinuclear antibody (ANA), anti-double-stranded (ds) DNA and complement were abnormal. This patient is now more than 1 yr post-stem cell transplant and is taking no immunosuppressive medication. Her serologies are normal, effusions have resolved, blood pressure is normal and renal function is markedly improved. The clinical and serological course of this patient is summarized here. METHODS: Autologous haematopoietic stem cells (HSC) were mobilized with cyclophosphamide (2.0 g/m2) and granulocyte colony-stimulating factor (G-CSF) (10 microg/kg/day). Stem cells were enriched ex vivo using CD34-positive immunoselection and reinfused after immunosuppression with cyclophosphamide (200 mg/kg) and antithymocyte globulin (ATG) (90 mg/kg). RESULTS: White blood cell engraftment with an absolute neutrophil count (ANC) of >500/microl (0.5 x 10(9)/l) and platelet engraftment with a non-transfused platelet count of >20000/microl (20 x 10(9)/l) occurred on day 10 and 14, respectively. Therapy was complicated by a cell lysis-like effect with hyperphosphataemia, hyperuricaemia, normal anion gap metabolic acidosis and transient exacerbation of renal insufficiency. CONCLUSION: This is the first autologous T-cell-depleted haematopoietic stem cell transplantation performed to treat lupus in an active flare. This patient has, for the first time since discase onset (13 yr ago), entered a complete clinical and serological remission which persists at >1 yr of follow-up. The durability of this remission is unknown.

Adult↗
PubMedDate not supplied

How CAM helps systemic lupus erythematosus.

The symptoms associated with systemic lupus erythematosus can vary in location and severity and often have life-altering effects. Because the disease is chronic, the use of traditional medical therapy may not bring about the maximum benefit in many cases. In light of this, many people diagnosed with lupus may turn to complementary and alternative medicine (CAM) therapies to help treat their disease. This article examines some of the common CAM methods used in addition to conventional medical treatment. Some points to consider include effectiveness, safety, cost, and ethical concerns associated with the use of CAM. The integration of these treatments into the medical regimen of those being treated for lupus is also considered.

Complementary Therapies↗
PubMed2003

Chronic pancreatitis associated with systemic lupus erythematosus in a young girl.

Systemic lupus erythematosus (SLE) is an uncommon etiology of pancreatic disease. Up to now, only 3 cases of chronic pancreatitis associated with SLE have been reported in adults. We report the case of a 14-year-old girl with SLE and calcifying chronic pancreatitis. At the age of 4 she was diagnosed with SLE. She presented with several acute exacerbations of SLE that were managed with prednisone and azathioprine. At the age of 9, she was admitted with abdominal pain and elevation of serum amylase and lipase levels; no gallstones were found on ultrasound, and treatment with azathioprine was withdrawn. Thereafter, she developed numerous episodes of acute pancreatitis. Later, an ERCP showed pancreatic calcifications and distortion of the main pancreatic duct, both findings consistent with established chronic pancreatitis. At the age of 14, her condition worsened progressively, and a surgical procedure (corporo-caudal spleno-pancreatectomy) was performed. The pathology specimen showed acinar atrophy and intense fibrosis. After surgery, the patient has remained pain-free and is enjoying a normal life.

Adolescent↗
PubMed1979

Severe pulmonary vascular disease in systemic lupus erythematosus.

A young woman with systemic lupus erythematosus (SLE) had clinical evidence of acute cor pulmonale. Autopsy disclosed vascular lesions in the lungs resembling those seen in advanced pulmonary hypertension. This case illustrates that severe pulmonary vascular disease may complicate SLE and mimic pulmonary thromboembolic disease.

Acute Disease↗
PubMed1983

Lupus band test in uninvolved oral mucosa in systemic lupus erythematosus.

In 42 patients with systemic lupus erythematosus, clinically normal oral mucosa was investigated with direct immunofluorescence technique for the presence of immunoglobulins G, A and M and complement factor C3 in the mucosal basement membrane zone (the lupus band test, LBT). Punch biopsies were performed in the posterior part of the hard palate (n = 39) or the lower labial mucosa (n = 3). The immunopathological observations were compared with clinical and serological data. The LBT was positive for IgM in 45% of the patients and trace amounts of IgM were found in another 19%. In 7 cases (17%) either IgG, IgA or C3 were found in addition to IgM and these patients all had a severe form of the disease, while the presence of IgM only was not correlated to clinical parameters.

Adult↗
PubMed1989

Bullous systemic lupus erythematosus.

Two patients with bullous systemic lupus erythematosus are reported. In one, the disease appears to have been caused by hydralazine. The cutaneous lesions of bullous SLE have not been previously reported in drug-induced lupus.

Adult↗
PubMed1995

Clinical trials of immunoadsorbent in systemic lupus erythematosus therapy.

Five patients with systemic lupus erythematosus (SLE) were perfused through an extracorporeal shunt filled with DNA-immunoadsorbent (DNA immobilized on carbonized resin beads). High concentrations of anti-DNA antibodies (36.4-67.0%) (binding percentage with 125I-DNA) in the serum of SLE patients were reduced to 13.8-53.0%, respectively. The highest removal percentage was 62.1%. Although the decline levels varied, the symptoms of patients, i.e., long-term severe joint pain, severe edema, hydropericardium, and ascites were all relieved considerably. The immunoadsorbent showed satisfactory blood compatibility.

Antibodies, Antinuclear↗
PubMed1993

A controlled study of peripheral neuropathy in systemic lupus erythematosus.

In 34 patients with systemic lupus erythematosus (SLE) and 34 age- and sex-matched healthy controls we performed standardized quantifiable neurological testing for neuropathic symptoms (Neuropathic Symptom Score) and deficits (Neurological Disability Score), as well as nerve conduction velocity studies (NCV) and determination of vibration thresholds (VT). SLE patients had more neuropathic symptoms and deficits than controls. Most quantitative and qualitative NCV attributes showed no difference between patients and controls. However, if categorized as NCV abnormalities of 2 or more nerves in each individual, a frequency of polyneuropathy of 21% was seen in SLE patients compared to 6% in controls. VT indicated a slight, but widespread, diffuse polyneuropathy in patients compared to controls.

Adolescent↗
PubMedDate not supplied

Deficiency of C4A is a genetic determinant of systemic lupus erythematosus in three ethnic groups.

Systemic lupus erythematosus (SLE) has shown associations with the major histocompatibility complex (MHC) class II DR antigens and class III complement components C2 and C4 in previous studies. The primary susceptibility locus has been difficult to identify, however, on account of linkage disequilibrium within the MHC. We have studied C4A and C4B distributions in 63 Caucasoid, 75 Chinese and 51 Japanese SLE patients. All three populations showed a statistically significant increase in C4A*Q0 (null) alleles when compared with 323 ethnically matched controls. We conclude that complete or partial deficiency of C4A is a genetic determinant of SLE common to these three ethnically distinct populations.

Alleles↗
PubMed1999

Hormonal regulation of tumor necrosis factor-alpha, interleukin-12 and interleukin-10 production by activated macrophages. A disease-modifying mechanism in rheumatoid arthritis and systemic lupus erythematosus?

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) frequently develop and progress in settings in which sympathoadrenomedullary and gonadal hormone levels are changing, e.g., during pregnancy, postpartum period, menopause, estrogen administration. This paper addresses the view that adrenal and gonadal hormonal deficiency facilitates excessive macrophage production of TNF-alpha and IL-12 that characterizes RA, whereas excessive estrogen action is suggested to play an essential role in the production of IL-10 in patients with SLE. Disease activity in SLE, in contrast to RA, appears to be associated with high-level production of IL-10, relative to the proinflammatory cytokines, TNF-alpha and IL-12. Accumulating data suggest that novel therapeutic approaches may ultimately be developed from continued investigation of the role of the neuroendocrine factors in RA and SLE.

Animals↗
PubMed1999

Sex hormones and pregnancy in rheumatoid arthritis and systemic lupus erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are autoimmune disorders with a preponderance in females. RA and SLE differ in their response to sex hormones. Disease development of RA is mitigated by estrogen and pregnancy whereas SLE tends to flare during pregnancy and in response to estrogen. Pregnancy improves the symptoms of RA in about 75% of pregnant patients, but relapses within six months postpartum in 90% of cases. RA is regarded as a T cell-mediated and TH1 immune response-driven disease. Pregnancy induces a shift from TH1 to TH2 immune response, increasing the anti-inflammatory cytokines IL-4 and IL-10, which may contribute to gestational amelioration of RA. Prospective studies of SLE pregnancies indicate that about 50% of patients experience a flare, however, with no permanent aggravation of the disease. Lupus nephritis, presence of antiphospholipid antibodies, and a previous history of pregnancy loss increase the risk of complications during pregnancy and fetal loss. The marked increase of estrogen and progesterone during pregnancy seems to enhance some of the manifestations of SLE. The shift to a TH2 immune response may trigger SLE manifestations that are dependent on humoral immune responses such as lupus nephritis. Another factor stimulating immune responses is the pituitary hormone prolactin, which has been found elevated in SLE patients of both sexes and correlated to disease activity in several studies. The hyperprolactinemia of lactation seems to influence postpartum behavior of SLE as well as RA.

Animals↗
PubMed1982

Methyl prednisolone pulse therapy in the treatment of systemic lupus erythematosus.

Twenty patients with active systemic lupus erythematosus (SLE) were treated with methyl prednisolone pulse therapy (MPPT) and followed up for up to 24 weeks (mean 18 weeks). Beneficial effects of MPPT were observed principally on arthralgia, pleuritic pain, vasculitic skin rash, pyrexia, and lymphadenopathy. The serological tests showing the most improvement were ds DNA binding and the serum C3 level. MPPT was found to be both safe and easy to administer. It may be of value in treating patients with SLE whose disease is not controlled by moderate doses of corticosteroids and may also enable the dose of maintenance corticosteroids to be reduced appreciably.

Female↗
PubMed1982

Inhibition of proliferative and suppressor responses in the autologous mixed lymphocyte reaction by serum from patients with systemic lupus erythematosus.

Serum from patients with systemic lupus erythematosus (SLE) prevents the proliferative response of normal T cells when stimulated by autologous or allogeneic non-T cells. The abrogation of proliferation in an autologous mixed lymphocyte reaction (AMLR) with SLE serum is associated with a lack of suppressor T cell generation. Fractionation of SLE sera on sucrose gradients reveals an 18-12 S peak of Raji cell binding material. Fractions with an S value of </=12 S show inhibitory activity in an AMLR.

Adult↗
PubMed1982

Lymphocyte destruction by antibody-dependent cellular cytotoxicity mediated in vitro by antibodies in serum from patients with systemic lupus erythematosus.

Sera from patients with systemic lupus erythematosus (SLE) were tested for the presence of IgG antilymphocyte antibodies that are capable of mediating antibody-dependent cellular cytotoxicity (ADCC) of peripheral blood lymphocytes (PBL) from normal donors. The effector cells employed were PBL autologous with the target PBL. Positive ADCC responses were obtained with serum from 5 SLE patients with severe active diseases. It is possible that ADCC is a mechanism by which IgG antilymphocyte antibodies in patients with SLE may mediate in-vivo lymphocytolysis.

Antibody-Dependent Cell Cytotoxicity↗