Anticardiolipin antibodies in serum and cerebrospinal fluid from patients with systemic lupus erythematosus

Anticardiolipin antibodies were studied in serum and cerebrospinal fluid from 32 consecutive patients with systemic lupus erythematosus, admitted for the assessment of neuropsychiatric disease. Ten of the 16 patients with active neuropsychiatric complaints showed positive anticardiolipin antibodies in cerebrospinal fluid, including eight with the simultaneous presence of antibodies in their sera. By contrast, only 2 of the 16 patients with headaches, lacking further data of neurological disease, revealed anticardiolipin antibodies in their cerebrospinal fluid. The assessment of Q-albumin index showed abnormal values in a subset of patients with active neuropsychiatric changes who showed positive cerebrospinal anticardiolipin antibodies, suggesting that an impairment of the blood brain barrier function may lead to a leakage of intrathecal antiphospholipid antibodies from systemic circulation. Additionally, few patients revealed normal Q-albumin values with high IgG-cerebrospinal fluid index suggesting increased intrathecal synthesis of autoantibodies. The study of anticardiolipin antibodies in cerebrospinal fluid was useful to detect active neuropsychiatric disease in systemic lupus erythematosus.     

The prevalence and clinical impact of fibromyalgia in systemic lupus erythematosus

OBJECTIVE: To ascertain the prevalence of fibromyalgia syndrome (FMS) in systemic lupus erythematosus (SLE) and to evaluate its clinical impact and relationship to SLE disease activity. METHODS: A cross-sectional analysis of 102 patients from a public hospital SLE clinic. Information was obtained on symptoms of FMS, disability, tender points, pain thresholds, and SLE disease activity. RESULTS: Twenty-two SLE patients (22%) met the American College of Rheumatology criteria for FMS, and another 24 (23%) had clinical FMS but did not meet the classification criteria. The patients who met the criteria for FMS had a significantly increased frequency and severity of symptoms commonly associated with FMS, and were much more likely to be unable to perform daily activities. The FMS patients also were less likely to be employed, and more likely to be divorced and to be receiving welfare or medical disability benefits. However, patients with and those without FMS did not differ in measures of SLE activity. CONCLUSION: FMS is very common in SLE patients, and accounts for many of the symptoms and much of the disability in these patients.     

Anticardiolipin antibodies are associated with pulmonary hypertension in patients with mixed connective tissue disease or systemic lupus erythematosus

Anticardiolipin antibodies (aCL) were studied in relation to pulmonary hypertension (PH) in 22 patients with mixed connective tissue disease (MCTD) or systemic lupus erythematosus (SLE). The mean pulmonary arterial pressure (mPAP) values were similar in the 12 MCTD and 10 SLE patients: 26 +/- 11 and 25 +/- 11 mm Hg, respectively. However, the frequency of PH was higher in SLE (60%) than in MCTD patients (33%). The titers of aCL were significantly higher in SLE (38 +/- 27 IU/ml) than in MCTD (17 +/- 7 IU/ml; p < 0.02). Two SLE patients with high titers of aCL had multiple cerebral infarction and transverse myelitis, and deep vein thrombosis, respectively. A significant correlation between the titers of aCL and mPAP was observed in patients with MCTD (p < 0.05), but not in patients with SLE.     

Transient monocular blindness and antiphospholipid antibodies in systemic lupus erythematosus

Cation binding to the monovalent cation selective channel, gramicidin A, is shown to induce changes in the dipolar and chemical shift observables from uniformly aligned samples. While these changes could be the result of structural or dynamic changes, they are shown to be primarily induced by through-bond polarizability effects when cations are solvated by the carbonyl oxygens of the peptide backbone. Upon cation binding partial charges are changed throughout the peptide plane, inducing large changes in the 13C1 chemical shifts, smaller changes in the 15N chemical shifts, and even smaller effects for the 15N-13C1 and 15N-2H dipolar interactions. These conclusions are substantiated by characterizing the 15N chemical shift tensors in the presence and absence of cations in fast-frozen lipid bilayer preparations of gramicidin A.     

Antiphospholipid antibodies in patients without systemic lupus erythematosus: neuroradiologic findings

PURPOSE: To study neuroradiologic findings in patients with hypercoagulability due to antiphospholipid antibodies (APAs). MATERIALS AND METHODS: Retrospective review of abnormal angiographic, computed tomographic, and magnetic resonance imaging findings was performed over a 14-month period in patients with APAs, no diagnosis of systemic lupus erythematosus, age less than 65 years, and no other cause of a hypercoagulable state. RESULTS: Fourteen patients (age range, 22-62 years) with APAs had abnormal results at neuroradiologic examination. Abnormal findings on cross-sectional imaging studies included large-artery (n = 3), lacunar (n = 5), and venous infarctions (n = 2); cortical atrophy (n = 5); white matter abnormalities (n = 3); and dural sinus thrombosis (n = 4). Abnormal angiographic findings included large-artery occlusions (n = 2), arterial narrowing that simulated vasculitis (n = 2), and transverse sinus thrombosis (n = 1). CONCLUSION: Presence of APAs should be suspected when no cause is apparent for either (a) an ischemic cerebrovascular event in young and middle-aged adults or (b) dural sinus or cerebral venous thrombosis (c) in patients with recurrent systemic arterial or venous thromboses, especially women with recurrent miscarriages.     

Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies. European Concerted Action on the Immunogenetics of SLE

OBJECTIVES: To evaluate, in a cohort of 566 patients with systemic lupus erythematosus (SLE) drawn from 11 European centres: (i) the prevalence of ANCAs and their subspecificities in a large series of European SLE patients; (ii) the possible associations of ANCA with the most common clinical manifestations of the disease; and (iii) whether ANCAs correlate with some of the autoantibodies commonly found in SLE. METHODS: ANCA detection was performed by indirect immunofluorescence (IIF), and by ELISA for lactoferrin (LF), myeloperoxydase (MPO), proteinase3 (PR3) and lysozyme (LZ) subspecificities. RESULTS: The prevalence of ANCA was 16.4% (IIF). The prevalence of LF was 14.3%, LZ 4.6%, MPO 9.3%, and PR3 1.7%. Our results show that ANCA is associated with certain clinical manifestations of SLE. In particular, positive correlations were found between IIF ANCA and serositis (p = 0.026), livedo reticularis (p = 0.01), venous thrombosis (p = 0.03) and arthritis (p = 0.04), while anti-LF antibodies were associated with serositis (p = 0.05) and livedo reticularis (p < 10(-3). Nevertheless, multivariate analysis demonstrated that other autoantibodies, such as aCL and SSA/Ro, are more closely correlated than ANCA with some of the aforementioned clinical features. CONCLUSION: Our results demonstrate that ANCA are detectable in SLE sera and that some of them are associated with particular clinical manifestations. Whether ANCA plays a direct pathogenetic role in the vascular damage of SLE or only represents an epiphenomenon or a marker of disease activity remains to be elucidated.     

Dehydroepiandrosterone in systemic lupus erythematosus: relationship between dosage, serum levels, and clinical response

OBJECTIVE: To examine in women with systemic lupus erythematosus (SLE) who participated in a clinical trial the relationship between daily dose of dehydroepiandrosterone (DHEA), serum levels of DHEA and DHEA sulfate (DHEAS), clinical effectiveness, and side effects. METHODS: Twenty-three women with mild to moderate SLE were treated with DHEA for a 6 month period. The starting dose was 50 mg/day, and monthly stepwise increases were allowed. Subjects were assessed monthly by the Systemic Lupus Erythematosus Disease Activity Index, Systemic Lupus Activity Measure (SLAM), Health Assessment Questionnaire, and other outcomes. Serum testosterone, DHEA, and DHEAS levels were obtained and side effects noted monthly. RESULTS: Statistically significant improvements were found in all lupus outcomes over 6 months. Serum DHEA and DHEAS levels correlated with the dose of DHEA. Serum DHEA and DHEAS correlated negatively with SLAM score. A second order regression analysis of serum DHEAS level versus SLAM score suggested that the optimal serum level of DHEAS was 1000 microg/dl. The most common side effect was acne. CONCLUSION: The clinical response to DHEA was not clearly dose dependent. Serum levels of DHEA and DHEAS correlated only weakly with lupus outcomes, but suggested an optimum serum DHEAS of 1000 microg/dl. Monitoring these serum levels appears to have limited clinical utility.     

Development of pathogenic anti-DNA antibodies in patients with systemic lupus erythematosus

The anti-DNA response is a hallmark of systemic lupus erythematosus (SLE). The precise mechanisms leading to anti-DNA antibody (Ab) production remain to be studied. Nonetheless, it is becoming clear that anti-DNA Abs cause inflammatory lesions not only via deposition of circulating immune complexes (IC) consisting of anti-DNA Ab and antigens (Ags), but also via in situ IC formation by cationic anti-DNA Abs. It is intriguing that cationic anti-DNA Abs are encoded by a unique germline Vkappa gene, A30, which encodes an extraordinary cationic light chain, whereas somatic mutations did not induce a cationic shift of electrical charge in human lupus nephritis, suggesting that the usage of a specific germline gene may confer the cationic charge (or pathogenicity) on anti-DNA Abs and that somatic mutations induce the affinity maturation of Abs. Whether cationic anti-DNA Abs will develop depends at least partly on the presence or absence of the germline A30 gene, since patients who lack this gene in the germline Vkappa repertoire did not develop severe lupus nephritis. Receptor editing, a mechanism for changing the affinity of the B cell Ag receptor [surface immunoglobulin (Ig) receptor] to avoid self-reactivity actually seems defective in patients with SLE because normal B cells edited the A30 gene, whereas SLE B cells express A30 mRNA. Thus, along with the importance of somatic mutations, polymorphisms of Ig Vkappa locus, and genetic predisposition, the failure of receptor editing may contribute to the development of pathogenic anti-DNA responses in humans.     

Platelet lactate dehydrogenase activity in systemic lupus erythematosus: correlation with anticardiolipin antibodies

OBJECTIVE: To evaluate lactate dehydrogenase (LDH) activity in platelet subpopulations in systemic lupus erythematosus (SLE) and to correlate platelet LDH activity with concentrations of anticardiolipin antibody (aCL). METHODS: Twelve female patients with SLE and 12 age matched female control subjects were studied. Platelets were separated on the Percoll gradient, their density values controlled by density marker beads. LDH activity was measured after platelet lysis, expressed as nU/fl. ELISA were used to measure levels of IgG and IgM aCL. RESULTS: A significant increase of LDH activity with a significant correlation to IgG and IgM aCL were found in small, light platelets with a volume < 5 mu 3 compared to large, dense platelets and to controls. LDH activity did not correlate with immunoglobulin classes, anti-DNA antibodies, and complement fractions in small and large SLE platelets. CONCLUSION: Our data suggest a possible chronic activation of subpopulations of small platelets in patients with SLE independent of thrombotic process. Low levels of aCL can mediate small platelet activation. Quantitative and qualitative analysis of the small, light platelets can serve a clinical diagnostic purpose as an in vivo platelet activation index in SLE.     

Relationship between endocrine, immune, and clinical variables in patients with systemic lupus erythematosus

OBJECTIVE: To assess the frequency of increased plasma prolactin (PRL) in patients with systemic lupus erythematosus (SLE) and to evaluate its relationship to other hormonal and immune variables. METHODS: Thirty-five patients with SLE with various levels of disease activity were studied. Plasma PRL, cortisol, growth hormone (GH) were determined by radioimmunoassay and interleukin 6 (IL-6) by ELISA: SLE activity was evaluated using the European Consensus Lupus Activity Measurement (ECLAM). RESULTS: Increased plasma PRL concentration (> 20 ng/ml) was recorded in 11 patients (31%). No correlation was found between plasma PRL and GH, IL-6, cortisol, or C-reactive protein, nor was any significant correlation observed between plasma PRL and the ECLAM score. Patients with hyperprolactinemia were, however, found to have been treated with higher doses of prednisone therapy than patients with normal plasma PRL. Further analysis of the relationship of plasma PRL and therapy showed that patients with SLE selected by the attending physician for prednisone therapy in doses > or = 10 mg/day were more frequently hyperprolactinemic. CONCLUSION: Our findings that patients with SLE with a more active form of the disease and who are less responsive to therapy had increased plasma PRL levels more frequently may be indicative of a potential relationship of hyperprolactinemia to severity of disease.     

Presence of antilamin antibodies in sera of patients with systemic lupus erythematosus

In this study, we characterized specifically-stained sera from patients with systemic lupus erythematosus (SLE) which had been shown to display the homogeneous or peripheral region of nuclei by indirect immunofluorescence (IIF). By western blotting, we demonstrated that in some cases there was a correlation between the peripheral or homogenous. IIF staining of nuclei by sera from patients with SLE and the presence of autoantibodies to lamins. Here we first report the presence of 2.2% anti-lamin autoantibodies in the sera among the 174 patients with SLE in China.     

Diffuse alveolar hemorrhage and systemic lupus erythematosus. Clinical presentation, histology, survival, and outcome

This article introduces the concept of men's unmet need for family planning and explains its programmatic relevance. Using data from Demographic and Health Surveys (DHS) of Ghana (1988, 1993) and Kenya (1989, 1993), married men are found to have high levels of unmet need for family planning that are comparable to, although slightly lower than, those for women. The importance of men's unmet need is demonstrated when the analysis is restricted to marital pairs in the DHS samples; trends in the joint unmet need of husbands and wives are shown to be closely associated with the nature of the fertility transitions occurring in Ghana and Kenya. Because of wide discrepancies found between husbands' and wives' unmet need statuses, family planning programs that foster spousal communication are likely to facilitate the transition to lower fertility.