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In vivo anti-nuclear antibodies in epithelial biopsies in SLE and other connective tissue diseases.

In vivo anti-nuclear antibody (ANA) was observed by direct immunofluorescence microscopy in epithelial cell nuclei in forty-four biopsies from thirty-three patients. The tissue containing the ANA was macroscopically normal in twenty-seven patients. The thirty-three patients with in vivo biopsy ANA included twenty-three with SLE, three with mixed connective tissue disease, two each with multi-system Sjögren's syndrome, dermatomyositis, and progressive systemic sclerosis, and one with rheumatoid arthritis. Features of sicca syndrome were noted in seventeen patients. The patterns of the in vivo biopsy ANA in the thirty-three patients were speckled (21), homogeneous (6), nodular (2), and both speckled and homogeneous (4). Complement was not detected in the epithelial cell nuclei. Immunoglobulin(s) and/or complement were deposited along the dermoepidermal junction in thirty-two of the forty-four biopsies, and in dermal blood vessels in twenty-two biopsies. Each patient had serum ANA against rat liver substrate; twenty-seven had high titre ANA (1 in 1000 or greater). Elevated levels of DNA-binding were found in twenty patients (61%), but the level of DNA-binding did not correlate with the intensity of in vitro biopsy ANA staining. Serum antibody to ribonucleoprotein (RNP) was present in eight of the twenty-three patients tested (35%), all eight patients having clinical features of sicca syndrome. Hypocomplementaemia was found in thirteen patients (40%), all of whom had active SLE. In vivo biopsy ANA appears to be a real phenomenon of unknown aetiology, and not an artifact, which is found in some patients with active multisystem autoimmune disease, especially SLE.

Adult↗

Systemic lupus erythematosus (SLE) induced by quinidine.

Only two definite cases of quinidine-induced systemic lupus erythematosus (SLE) are reported in the English-language literature. We have treated five patients who had an SLE-like syndrome while receiving quinidine. Symptoms, signs, and abnormal laboratory values improved after quinidine therapy was discontinued and prednisone therapy was started. The disease did not return after steroids were withdrawn. These cases indicate that quinidine can indeed cause an SLE-like syndrome.

Aged↗

Procainamide-induced SLE and lymphoreticular disorders.

A 56-year-old male patient diagnosed as a case of procainamide-induced systemic lupus erythematosus (SLE) was found to have a lymphoproliferative disorder at postmortem examination.Contrary to other immune disorders, the association of SLE with neoplasia is a rare occurrence. The present case raises the question of whether a relationship exists between the lupus diathesis and lymphoreticular neoplasia. The study of the incidence of neoplasia in families of patients with SLE may prove helpful in establishing this relationship.

Aortic Diseases↗

Complement-mediated solubilization of immune complexes. Solubilization inhibition and complement factor levels in SLE patients.

Thirty-two of 36 serum samples from 19 SLE patients showed reduced capacity to mediate complement-dependent solubilization of immune complexes (IC). SLE patients with nephritis exerted the lowest complement-mediated solubilization capacity (CMSC) whereas sera from patients with inactive disease gave the highest CMSC values, with three out of four samples within the normal reference range. Thirty-five of the 36 serum samples showed inhibition of CMSC in a newly developed CMSC inhibition assay. The strongest CMSC inhibition was exerted by sera from newly discovered cases of SLE who received no medical treatment and the lowest inhibition by sera from patients with inactive disease. There was a significant negative correlation between CMSC and CMSC inhibition (r = -0.67, P less than 0.001). Sera with low concentrations of C1q, C3, factor B or high C3d levels showed markedly reduced CMSC values. Pronounced CMSC inhibition was observed only in samples with normal or high factor H values. No significant correlation was found between CMSC or CMSC inhibition and circulating IC levels, but pronounced CMSC inhibition was registered only in strongly IC positive sera.

Adolescent↗

Antibodies to Mi-1 in SLE: relationship to other precipitins and reaction with bovine immunoglobulin.

Precipitating antibodies to Mi-1, a protein antigen purified from calf thymus nuclear extract, have been reported in a small percentage of patients with dermatomyositis (DM) but not in patients with other connective tissue diseases or controls. Mi-1 shares certain characteristics with immunoglobulin, including the ability to react with rabbit anti-bovine immunoglobulin G (BIgG). A more extensive survey for anti-Mi-1 has been performed, involving 51 normal controls, 67 patients with polymyositis (PM) or DM, 47 patients with rheumatoid arthritis (RA), 41 SLE patients without any other precipitating antibodies to saline extractable tissue antigens on routine testing, and 247 patients, many with SLE, known to have other precipitins. Anti-Mi-1 was found in 13 patients from the latter group (5.25%) and two patients with PM or DM (3.0%), and was not found in other groups. It was found in seven of 95 (7.4%) with anti-nRNP, three of 32 (9.4%) with anti-Sm (with or without anti-nRNP) and three of 120 (2.5%) with anti-Ro (SSA). Anti-Mi-1 cross-reacts directly with BIgG but differs from ordinary rheumatoid factor in its frequent reaction with Fab2 fragments and restricted species specificity. Thus, anti-Mi-1 can be found in patients with diseases other than DM, including SLE, most often in patients with antibodies to nRNP.

Arthritis, Rheumatoid↗

A comparison of serologic reactivity among SLE patients with or without anti-Ro (SS-A) antibodies.

The serum from 112 patients with systemic lupus erythematosus (SLE) was examined to compare serologic reactivity among anti-Ro positive and anti-Ro negative patients. While hypergammaglobulinemia, rheumatoid factor (RF) and elevated Clq binding were significantly more frequent among the anti-Ro positive group there was no increase in the frequency of anti-dsDNA antibody measured by the Farr assay or antibodies to ssDNA, dsDNA, poly dG . poly dC, poly (dA-dT) and cardiolipin measured by ELISA. Patients with the highest levels of anti-DNA antibody by the Farr assay did not have any increased frequency of anti-Ro antibodies. We concluded that anti-Ro and anti-DNA antibodies are independently regulated. The frequent occurrence of RF in anti-Ro positive SLE patients may provide a useful screening assay for this autoantibody among pregnant SLE patients.

Antibodies, Antinuclear↗

Suppressor cell defect in SLE: relationship to native DNA binding.

Recent evidence suggests the presence of a suppressor T cell defect in systemic lupus erythematosus. We confirm the presence of such a defect and find a strong quantitative correlation between the loss of suppressor T cell function and the activity of SLE as measured by the presence of antibodies to native DNA. In addition, the serum of patients with active SLE contains a soluble factor which when incubated with normal peripheral blood lymphocytes induces a suppressor T cell defect. These data are consistent with the suppressor cell defect being involved in the propagation and possible the pathogenesis of SLE, and suggests a positive feedback mechanism whereby a suppressor cell defect results in autoantibodies including antibody to suppressor cells.

Adult↗

Reticuloendothelial Fc receptor function in SLE patients. I. Primary HLA linked defect or acquired dysfunction secondary to disease activity?

Reticuloendothelial system (RES) Fc receptor-mediated immune clearance was measured in 18 patients with systemic lupus erythematosus (SLE). Only two patients, with major disease activity, had a prolonged T 1/2 of the blood disappearance curve of injected IgG coated red cells in comparison to 22 healthy controls. Circulating immune complexes (CIC) were studied with three methods: PEG precipitation, C1q-ELISA and the indirect granulocyte phagocytosis test (IGFT). The T 1/2 of the blood disappearance curve related significantly to the IGFT (r = 0.55, P less than 0.05) and not to the PEG and C1q-ELISA test. Although HLA-DR3 phenotype frequency was significantly increased in our SLE population (P less than 0.05), it was not related to Fc receptor function. Similarly, HLA-DR2 phenotype was not related to RES Fc receptor function. These data do not support the concept that a genetic HLA linked defect in reticuloendothelial Fc receptor function is a primary cause of SLE, predisposing the inflicted individual to immune complex deposition. However, Fc receptor-mediated immune clearance seems to be related to disease activity itself and to levels of CIC.

Adolescent↗

Evidence for intrinsic cellular defects of 'complement' receptor-mediated phagocytosis in patients with systemic lupus erythematosus (SLE).

Fc and 'complement'-mediated phagocytosis of pre-opsonized yeast has been studied in monocytes from 18 patients with SLE. Monocytes from nine of 18 patients had depressed complement-mediated phagocytosis (P = 0.0001, Fishers exact test) but only three of 18 had depressed Fc-mediated phagocytosis (NS, Fishers exact test). Although reduced complement-mediated phagocytosis was correlated with increased frequency of disease manifestations (P less than 0.003, rank correlation) there was no correlation with serum DNA or C1q binding activity, C3 or C4 levels. Serum from SLE patients with depressed phagocytosis did not inhibit phagocytosis by normal monocytes. The data suggests the presence of intrinsic abnormalities of monocyte receptor function in SLE and the nature of the 'complement' receptors involved is discussed.

Adult↗

Transfer of renovascular hypertension and coronary heart disease by lymphoid cells from SLE-prone mice.

Among early life SLE mice, the male F1 hybrids of NZW X BXSB crosses are unique by their much earlier onset of glomerulonephritis (GN) (evident by 2 1/2 months of age), progressive hypertension, and high frequency of degenerative cardiovascular disease (CVD) with myocardial infarcts. In contrast, their female counterparts and the other kinds of SLE mice have later onset of GN, minimal hypertension, and lower incidence of CVD. The etiopathogenesis of these F1 males' disease was investigated by reciprocally transferring syngeneic lymphoid cells into lethally irradiated F1 male and female mice. As a result, female recipients of male lymphoid cells developed accelerated GN, hypertension, and severe CVD, but the male recipients of female lymphoid cells (at comparable ages) had delayed SLE, remained normotensive, and were spared coronary or myocardial damage. These findings strongly indicate that the hypertension and CVD of these F1 males originate from immunologic abnormalities rather than from other nonlymphoid factors.

Animals↗

Monocyte in vitro function in systemic lupus erythematosus (SLE). I. A clinical and immunological study.

A previous article (34) has shown that normal monocytes cultivated in presence of several sera from patients with SLE displayed low yeast cell phagocytosis. In the present extended study it was investigated whether the level of phagocytic activity (PA) had any relation to clinical and laboratory expressions of disease activity. The results reveal that, in addition to hypocomplementaemia and cryoglobulinaemia, low PA was associated with high clinical disease activity including arthritis, rash and nephritis and high titres for anti-nDNA. It was also found that PA improved as the disease activity declined. These findings suggest that this in vitro phagocytosis test might be used as an indirect method for detecting clinically relevant circulating immune complexes in SLE. Furthermore, it might be used as a guide in the evaluation of disease activity in severe SLE. The mechanism behind impaired phagocytosis was not elucidated in this study. Inadequate opsonization of the yeast cells or blocking of the monocyte surface receptors by immune complexes were suggested as possible explanations.

Adolescent↗

C-reactive protein in the differential diagnosis between infection and disease reactivation in SLE.

Fifty of 197 systemic lupus erythematosus (SLE) sera had 2 + positive C-reactive protein (CRP) determinations by precipitation in capillary tubes. All but 3 of these 50 sera had been taken at the time of infection whereas 80 of the 115 sera taken at the time of SLE activity without infection were negative for CRP. Thirty-two of the 35 CRP positive sera from patients with active lupus were obtained during intercurrent infection. CRP determinations in capillary tubes are clinically useful in distinguishing disease reactivation from intercurrent infection in SLE. These findings confirm a study using the same method for CRP determination. Discrepancy with another study may be due to the use of a different method.

Bacterial Infections↗

Induction of experimental SLE in naive mice by immunization with human polyclonal anti-DNA antibody carrying the 16/6 idiotype.

Recently, the induction of SLE in naive mice employing monoclonal anti-DNA antibodies (anti-DNA Ab) carrying the pathogenic idiotype 16/6 (16/6 Id) has been reported. In the current study we report on the induction of experimental SLE by polyclonal IgG anti-DNA Ab derived from a patient with active SLE and carrying the 16/6 Id. Two different experiments were conducted in which BALB/c mice were immunized in the footpads with 1 microgram/ml or 5 micrograms/ml of anti-DNA Ab. The first experiment showed the appearance in the immunized mice of high titre anti-DNA Ab together with antinuclear antibodies, alopecia and proteinuria. In the second experiment we compared, as immunizing agents, 16/6 positive anti-DNA Ab and 16/6 negative anti-tetanus toxoid antibodies (anti-TT Ab) obtained from the serum of the same patients. Our results show that only mice immunized with 16/6 positive antibodies produced anti-DNA Ab, while mice immunized with anti-TT Ab did not show any DNA-binding activity but, surprisingly, developed high titre anti-cardiolipin antibodies.

Alopecia↗

[A case of benign intracranial hypertension associated with systemic lupus erythematosus (SLE) showing diffuse white matter lesions on MRI].

We describe a 35-year-old woman with benign intracranial hypertension (BIH) secondary to systemic lupus erythematosus (SLE). She had low grade fever and skin eruptions, but neurological examination revealed no abnormal findings. Antinuclear and anti ds-DNA antibodies were positive, and complements were decreased. MRI demonstrated diffuse hyperintense white matter lesions on T2-weighted imaging. Mild bilateral papilledemas developed in the fundi, when her headache was exacerbated. The cerebrospinal fluid (CSF) pressure was 550 mmH2O. Cerebral angiography showed no cerebral sinus thrombosis. She was diagnosed as BIH secondary to SLE. Since RI cisternography revealed remarkably delayed absorption of the CSF, it was speculated that the CSF absorption by arachnoid villi would be probably disturbed in association with some autoimmune mechanisms by SLE. The subsequent rise of intraventricular pressure may result in retrograde transependymal flow of the CSF and the diffuse hyperintense white matter lesions on MRI.

Adult↗

[Methylprednisolone pulse therapy for SLE patients with CNS disorder].

A clinical trial was conducted in 22 SLE patients with central nervous system (CNS) disorder in which the efficacy of pulse methylprednisolone suleptanate at the dose of 400 mg or 800 mg (as methylprednisolone) was assessed. The symptoms of CNS disorder disappeared within 40 days after pulse therapy in all of the 16 patients with organic brain syndrome (OBS). No improvement in the symptoms took place in any but one of the five patients who had cerebrovascular disorder. One SLE patient with depression showed improvement 55 days after pulse therapy. In the patients with OBS who had not received pulse therapy until 28 days or more after onset of CNS disorder, the symptoms disappeared in 20 days or more in both 400 mg and 800 mg dose groups. On the other hand, five of the six patients given the dose of 800 mg within 10 days of occurrence of the disease experienced a complete relief of the symptoms in 10 days after pulse therapy. However, at least 13 days were required for complete relief in all the four patients of the 400 mg group. The adverse reactions reported consisted of hyperlipemia, diabetes mellitus, and infections such as thrush or herpes zoster. The above results suggest that methylprednisolone pulse therapy is useful in the treatment of CNS disorder associated with SLE, particularly in patients with OBS who are given the dose of 800 mg early after onset of the disease.

Adolescent↗

Hereditary C2 deficiency in systemic lupus erythematosus and acquired complement abnormalities in an unusual SLE-related syndrome.

Early study of kindreds with C2 deficiency indicated that absence of C2 had no detrimental effect on affected individuals. Studies of additional kindreds, however, show a high incidence of SLE and other connective tissue diseases among homozygous C2-deficient members. A group of patients with an unusual SLE-related syndrome is described. In common with certain SLE patients they have marked depression of early complement components and presence of circulating Clq precipitins. It is suggested that early complement components are involved in specific host defense mechanisms and deficiencies of these components may predispose to such diseases.

Antibodies, Antinuclear↗

[Occurrence of bronchiolitis obliterans organizing pneumonia (BOOP) in a flare-up stage of systemic lupus erythematosus (SLE)].

A 33-year old housewife who developed BOOP in a flare-up stage of SLE was reported. She had been treated for Hashimoto's thyroidtis since the age of 18. When the patient was 21 years old, she noticed polyarthritis and subcutaneous nodules. She had a high titer of rheumatoid factor and a diagnosis of rheumatoid arthritis was made. At the age of 23, ulnar drift was noted despite the lack of subjective and objective signs of active articular inflammation. At the age of 25, she developed dry eyes and dry mouth, and at the age of 27, photosensitivity was experienced. At the age of 28, she was first admitted to our department and diagnosis of Sjögren's syndrome and SLE was made. Since then, she had been treated by corticosteroid and remained in a stable condition. In January 1991, she developed facial erythema, dry cough and edema of the lower extremities. Laboratory findings included profuse proteinuria, hypoalbuminemia, hyperlipidemia, elevated anti-DNA titer, depressed serum complements. Chest X-ray films showed a presence of patchy non-segmental infiltrates in both lung fields. TBLB specimen showed the characteristic findings of BOOP described by Epler at al. She had marked ulnar deviation at the MCP joints bilaterally and X-ray findings were consistent with Jaccoud's arthropathy. The pulmonary lesions and nephrotic syndrome responded to the combined therapy of prednisolone and immunosupressants. An occurrence of BOOP associated with flare of SLE indicates that immunological mechanisms might be involved for development of BOOP. Indeed, review of the literature shows that substantial numbers of patients with BOOP had clinical and serological overlapping findings with autoimmune diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Incidence of SLE in a patient thymectomized for myasthenia gravis].

The appearance of systemic lupus erythematosus (SLE) as well as thymopoietin (TP3) treatment in a patient who has undergone thymectomy because of myasthenia gravis (MG) is described. To the authors' knowledge this is the first case of this treatment upon the diagnoses above. The therapy was performed for 12 weeks by the Hungarian Thymotrinan (TP3) preparate according to a previous protocol worked out for Hodgkin's disease. At the beginning and during therapy, cellular and humoral immune parameters were monitored. Twenty months after the therapy the patient has remained in clinical remission for both diseases, MG and SLE, respectively. There is a brief survey of the biochemistry of thymic hormones as well as their clinical use, especially in the treatment of autoimmune disorders. The relative rarity of SLE after operative treatment of MG is under discussion together with the effectiveness of substitutional thymic hormone therapy.

Acquired Immunodeficiency Syndrome↗