bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of hemostatic markers and thrombomodulin in systemic lupus erythematosus: evidence for a prothrombotic state
Authors: Kiraz S , Ertenli İ , Benekli M , Haznedaroğul İ C , Çalgüneri M , Çelik İ , Apraş Ş , Kirazlil Ş
Published: November 2003

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder with overwhelming thrombotic states. The precise pathogenetic mechanisms underlying the prethrombotic state in SLE is not filly understood, but interactions between the antiphospholipid antibodies and antigen targets on the coagulation components have been incriminated to play fundamental roles. To evaluate this issue, 34 women with antiphospholipid antibody negative SLE were investigated for molecular markers of blood coagulation and fibrinolytic activity: prothrombin fragmentl+2 (PF1 +2), thrombin-antithrombin complex (TAT), plasmin--a2-antiplasmin inhibitor complex (PAP), and tissue factor pathway inhibitor (TFPI). We also analysed plasma soluble thrombomodulin (sTM) levels. SLE disease activity was determined using the SLE Disease Activity Index (SLEDAI). Concentrations of TAT, PAP, PFl + 2 and sTM were significantly elevated (P < 0.0001, P = 0.0002, P < 0.0001, and P < 0.0001, respectively), while TFPI antigen levels were found to be reduced (P < 0.0001) in patients with SLE compared to the control group. In patients with active SLE, anti-ds DNA levels were correlated positively with plasma TAT (P < 0.05), PFl + 2 (P < 0.05), and sTM (P < 0.01) concentrations and negatively with plasma TFPI levels (P < 0.05). SLEDAI scores were correlated positively with plasma TAT (P < 0.01), PFl + 2 (< 0.01), and sTM (P < 0.01) levels. This study illustrates that both a prethrombotic state and a compensatory fibrinolytic process secondary to subclinical intravascular coagulation might coexist in SLE with elevated sTM levels, indicating impaired endothelial functions.
Mycophenolate mofetil for the treatment of systemic lupus erythematosus: an open pilot trial
Authors: Gaubitz Markus , Schorat Annette , Schottel Heiko , Kern Peter , Domschke Wolfram
Published: November 2003

Objective: To investigate the effectiveness and safety of mycophenolate mofetil in patients with systemic lupus erythematosus who were inadequately controlled with corticosteroids, antimalarials, and other immunosuppresive agents.

Methods: Ten patients with systemic lupus erythematosus (SLE) were treated with 1500-2000 mg mycophenolae mofetil (MMF) daily for a median observation time of 11.2 ± 2.4 (8-16) months in an open clinical trial. The effectiveness and safety of treatment were analyzed using an established disease activity score, clinical status, and laboratory parameters.

Results: All patients improved under treatment with no or only minor side effects. The disease activity score (SLAM) decreased statistically significantly from a median of 15.6 ± 5.5 to 9.9 ± 4.1 after three months (P < 0.01) and to 8.0 ± 3.3 after six months (P < 0.01). Hematologic parameters did not change significantly whereas a reduction of inflammatory markers was observed. Four patients with SLE-nephritis already treated with cyclophosphamide pulse therapy continuously showed a slight improvement of renal function. Prednisolone dosages could be reduced significantly from a median level of 10.0+ 5.1 mg/d before treatment to 4.6 ±3.5 mg/d after six months (P < 0.01).

Conclusion: Mycophenolate mofetil is a promising option in immunosuppressive treatment of patients with moderate and severe systemic lupus erythematosus who did not show a satisfactory response to other immunosuppressives.
Relationship between clinical features and binding domains of anti-prothrombin autoantibodies in patients with systemic lupus erythematosus and antiphospholipid syndrome
Authors: Akimoto T , Akama T , Kono I , Sumida T
Published: November 2003

Autoantibodies against prothrombin, including lupus anticoagulant antibodies (LAC), have been identified in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). To identify the epitopes of LAC in patients with SLE and APS, we analyzed B cell epitopes of anti-prothrombin Abs. Prothrombin was purified from fresh plasma samples from healthy subjects, and fragmented by thrombin. Two fragments (prethrombin-1, 50kDa, and fragment-i, 22 kDa) were separated and used for further experiments. The two fragments were coated on irradiated plate and the binding activities of sera from 13 patients with anti-prothrombin Abs (SLE, 7; APS, 4; SLE + APS, 2) were determined by using ELISA. The assay was conducted under the following conditions: use of irradiated plates, and TBS containing Tween-20. We detected two types of anti-prothrombin Abs. The first was anti-prethrombin-l (n = 5) while the other was Ab against fragment-I (n = 8). There were no patients with Abs that showed binding activities to both fragments. A higher proportion of patients with thrombosis were positive for anti-prethrombin-I Abs (80%) than for anti-fragment-I Abs (25%). Two patients with anti-prethrombin-I Ab were positive for LAC and negative for anti-cardiolipin-f32 glycoprotein I antibody (aCL-I32GPI). Our results strongly support the notion that both prethrombin-I and fragment-1 on prothrombin molecule are B cell epitopes.
A study of 20 SLE patients with intravenous immunoglobulin clinical and serologic response
Authors: Levy Yair , Sherer Yaniv , Ahmed Alaa , Langevitz Pnina , George Jacob , Fabbrizzi Fabrizio , Terryberry Jeff , Meissner Martyna , Lorber Margalit , Peter James B , Shoenfeld Yehuda
Published: November 2003

Objective: To test the clinical response of systemic lupus erythematosus (SLE) patients to intravenous immunoglobulins (IVIg), and whether the clinical response of IVIg treatment in SLE is accompanied by modification of SLE-associated autoantibodies/antibodies (Abs) and complement levels.

Methods: Twenty SLE patients were treated with high-dose (2 g/kg) IVIg monthly, in a 5-d schedule. Each patient received between 1-8 treatment courses. They were evaluated for the clinical response, Systemic Lupus Activity Measure (SLAM) score before and after IVIg, levels of antinuclear antibody (ANA), dsDNA (double-stranded DNA), SS-A or SS-B, ENA (extractable nuclear antigens), C3 and C4 levels before and after the treatment, and before and after each treatment course.

Results: A beneficial clinical response following IVIg treatment was noted in 17 out of 20 patients (85%). Few clinical manifestations responded more to treatment: arthritis, fever, thrombocytopenia, and neuropsychiatric lupus. In 9 patients evaluated before and after IVIg, mean SLAM score decreased from 19.3 ± 4.7 to 4 ± 2.9 (P < 0.0001). There was a tendency towards abnormal levels of complement and Abs before IVIg courses among the treatment responders compared with the non-responders, and similarly the former tended to have normalization of their abnormal levels more than the latter. These differences were found statistically significant only with respect to C4 and SS-A or SS-B levels before IVIg courses.

Conclusion: IVIg has a high response rate among SLE patients. A combination of clinical manifestations, Abs and complement levels may aid in the future in predicting who among SLE patients will benefit more from IVIg treatment.
Systemic lupus erythematosus in Lebanon
Authors: Uthman Imad , Nasr Fuad , Kassak Kassem , Masri Abdul-Fattah
Published: November 2003

The present study describes the clinical characteristics of patients with systemic lupus erythematosus (SLE) from the American University of Beirut Medical Center (AUBMC), one of the largest teaching hospitals in Lebanon. This is a retrospective chart review of 100 SLE patients seen over a 20 y period. There were 86 females and 14 males, with a median age of 26 y. 85 patients were Lebanese and 15 patients were Palestinians. The main clinical features were arthritis and/or arthralgias seen in 95% of our patients, followed by malar rash (52%), and renal involvement (50%). Of the hematological manifestations, thrombocytopenia was most commonly seen in 33% of patients, followed by leucopenia in 17% and hemolytic anemia in 10% Oral ulcers and serositis were both seen in 40% of patients. Less frequent manifestations included discoid lupus (19%), neuropsychiatric manifestations (19%), and photosensitivity (16%). Antinuclear antibodies were detected in 87% of patients, whereas anti-DNA antibodies were seen in 50% of cases. 25 patients (25%) had a false-positive VDRL. A comparison between our findings and 3 other Arab SLE groups revealed a higher incidence of oral ulcers, discoid lupus, articular manifestations, thrombocytopenia and false-positive VDRL, and a lower incidence of photosensitivity, leucopenia, neuropsychiatric manifestations, and anti-DNA antibodies.
Minocycline-induced clinical and biological lupus-like disease
Authors: Tournigand Christophe , Genereau Thierry , Prudent Murielle , Diemert Marie-Claude , Herson Serge , Chosidow Olivier
Published: November 2003

A 14-year-old girl developed maculopapular rash, myalgias, arthralgias and myocarditis with elevated anti-nuclear and anti-double-stranded DNA antibodies. She was taking minocycline for acne and all symptoms resolved when this treatment was stopped. The patient has no evidence of disease one year after onset of symptoms. Clinicians should be aware of minocycline's responsibility in inducing lupus-like disease.
Hughes syndrome associated with cytomegalovirus infection
Authors: Uthman I , Tabbarah Z , Gharavi A E
Published: November 2003

We report the case of a patient with an acute cytomegalovirus (CMV) infection who developed Hughes syndrome, manifested by a common iliac vein thrombosis. IgM anticardiolipin antibodies (aCL) appeared with the onset of the infection, followed later by IgG aCL. Five months later, both IgM and IgG aCL levels disappeared from the serum. This is the second case of Hughes syndrome associated with CMV infection to be reported in the literature.
‘Sustained remission’ in a case of SLE following megadose cyclophosphamide
Authors: Mittal G , Balakrishna C , Mangat G , Joshi V R
Published: November 2003

Cytotoxic therapy, especially with cyclophosphamide in the dose 8–20 mg/kg used as intermittent pulses, has been shown to improve both patient and renal survival in systematic lupus erythematosus (SLE), but to date there is no cure for the disease. Owing to the paucity of recognisable clones, the rationale and goal of cytotoxic immunosuppressive therapy in the treatment of immune-mediated diseases as against malignancies is to suppress the aberrant infiammation and immune-mediated reactions responsible for tissue damage, without dangerously suppressing the normal host defence mechanism(s). We report the case of a patient suffering from SLE with nephritis who has remained in sustained remission over the past 8 years without any maintenance therapy following an accidental administration of a single dose of 5000 mg of intravenous cyclophosphamide (44.2 mg/kg body weight). The patient recovered fully from pancytopenia following the injection. Presently, she is asymptomatic and working gainfully. Her laboratory parameters including blood counts, urine analysis, FANA and anti-dsDNA have reverted to normal. Cyclophosphamide in the dose of 30–160 mg/kg has been safely and effectively used in various neoplastic conditions with the aim of destroying every possible tumour cell. The experience of the present case suggests that such an approach may be applicable to SLE.
Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations
Authors: Sabbadini M G , Manfredi A A , Bozzolo E , Ferrario L , Rugarli C , Scorza R , Origgi L , Vanoli M , Gambini O , Vanzulli L , Croce D , Campana A , Messa C , Fazio F , Tincani A , Anzola G , Cattaneo R , Padovani A , Gasparotti R , Gerli R , Quartesan R , Piccirilli M , Farsi A , Emmi E , Domeneghetti M , Piccini C , Massacesi L , Pupi A , De Cristoforis M , Danieli M , Candela M , Fraticelli P , Bartolini M , Salvolini U , Danieli G , Passaleva A
Published: November 2003

Objective: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations.

Methods: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)).

Results: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory.

Conclusions: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.
Primary Sjögren's syndrome in the elderly: clinical and immunological characteristics
Authors: García-Carrasco M , Cervera R , Rosas J , Ramos-Casals M , Morlá R M , Sisó A , Jimé S , Pallaré L , Font J , Ingelmo M
Published: November 2003

The objective of the study was to determine the clinical and immunological characteristics of primary Sjoögren's syndrome (SS) in patients with an older onset of the disease. We included 223 consecutive patients (204 female and 19 male; mean age at onset 53 years; range 15-87 years) visited in our Units. All patients were white and fulfilled four or more of the diagnostic criteria for SS proposed by the European Community Study Group in 1993. Disease onset was determined on the basis of the appearance of symptoms strongly suggestive of SS. In 31 patients the onset of disease occurred after the age of 70 years, and they represent the elderly-onset group described in this report. The remaining 192 patients presented disease onset before the age of 70 years, and they represent the younger-onset group.

Of the 31 (14%) patients with elderly onset of primary SS, 26 were female and 5 male, and the disease onset occurred between 70 and 87 years (mean 74 years). The most common extraglandular manifestations were articular involvement (29%), hepatic involvement (20%), peripheral neuropathy (16%) and interstitial pneumopathy (13%). When compared with patients with a younger onset, the prevalences of glandular and extraglandular manifestations and immunological features (cryoglobulinemia, hypocomplementemia and positivity for RF, anti-Ro/SS-A or anti-La/SS-B) were similar in both groups.

In conclusion, although primary SS is typically a disease of middle-aged adults, clinicians should note that it may be diagnosed frequently among elderly patients. However, we could not found any notable differences in clinical and immunological characteristics of patients with elderly onset of primary SS.
Decreased expression of the p21ras stimulatory factor hSOS in PBMC from inactive SLE patients
Authors: Rapoport M J , Mor A , Amit M , Rosenberg R , Ramot Y , Mizrachi A , Wysenbeek A J
Published: November 2003

Expression of the p21ras protooncogene is reported to be increased in animal models and in patients with SLE. However, the expression of p21ras regulatory elements has not been determined. We determined the expression of p21ras, and its regulatory elements p120-ras-GAP and hSOS, in PBMC of 10 patients with inactive SLE (mean SLEDAI score 1.8 0.53) and 10 age-and sexmatched healthy controls. No difference was found between the two groups in the levels of p21ras (3760–513 and 3367–335, P = 0.25) and ras-GAP (1048–261 and 1534–247, P = 0.11) in patients and controls, respectively. In contrast, levels of hSOS were significantly decreased in patients as compared to controls: 955 218 and 2306 327, P = 0.002, respectively. The mitogeninduced proliferative response was comparable in the two groups: SI 20.8 4.2 and 15.03 4.9, P = 0.135, in patients and controls, respectively. Taken together, our data demonstrate that nonactive SLE patients are characterized by reduced hSOS expression and underscore the need for a comprehensive evaluation of p21ras pathway in these patients.
Integrin signalling defects in T-lymphocytes in systemic lupus erythematosus
Authors: Ng T TC , Collins I E , Kanner S B , Humphries M J , Amft N , Wickremasinghe R G , D'Cruz D , Nye K E , Morrow W JW
Published: November 2003

Objective: To establish the relationship between T cell responses to integrin coreceptor stimulation and B cell hyperreactivity as measured by pathologic autoantibody production.

Methods: Peripheral blood mononuclear cells from 42 patients with SLE according to the American Rheumatism Association criteria were examined for their ability to adhere to plateimmobilised fibronectin. Co-stimulation assays were performed on the same cells using anti-CD3 antibody alone or co-immobilised with an anti-b1-integrin antibody. Proliferative responses were measured by 3[H]thymidine pulsing on day 3 and activation was determined using a commercial protein kinase C assay, the protocol being established by our group in association with Promega. b1-Integrin expression was established by FACS analysis.

Results: An impaired PKC response to integrin-mediated activation was found in T-lymphocytes from 6=21 (29%) SLE patients, which correlated significantly with an absence of anti-dsDNA antibody in patient sera, irrespective of prednisolone treatment. Integrin co-stimulation of TcR/CD3-induced proliferation and T cell adhesion to fibronectin were also impaired among 5=21 (24%) and 6=15 (40%) patients studied, respectively.

Conclusion: We hypothesise that the integrity of b1-integrin signalling pathways may influence pathological antibody production in SLE by affecting T-lymphocyte activation and interactions between T and Blymphocytes.
Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE
Authors: Wu R , Svenungsson E , Gunnarsson I , Andersson B , Lundberg I , Elinder L Schäfer , Frostegård J
Published: November 2003

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. β-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to β2GP1.

There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.
Systemic lupus erythematosus complicated by necrotizing fasciitis
Authors: Mendez E A , Espinoza L M , Harris M , Angulo J , Sanders C V , Espinoza L R
Published: November 2003

A case of necrotizing fasciitis (NF) is described in a 46-year-old woman with recent onset systemic lupus erythematosus (SLE). Deep-tissue infections are more common in SLE patients on high-dose corticosteroids, but, to our knowledge, this is the second case described in association with SLE. Although NF may initially be difficult to diagnose, the presence of marked systemic symptoms out of proportion to the local findings should suggest the correct diagnosis. NF diagnostic criteria, treatment and prognosis are discussed.
Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes
Authors: Chapman J , Cohen-Armon M , Shoenfeld Y , Korczyn A D
Published: November 2003

Antiphospholipid antibodies (aPL) are associated with neurological diseases such as stroke, migraine, epilepsy and dementia and are thus associated with both vascular and non-vascular neurological disease. We have therefore examined the possibility that these antibodies interact directly with neuronal tissue by studying the electrophysiological effects of aPL on a brain synaptosoneurosome preparation. IgG from patients with high levels of aPL and neurological involvement was purified by protein-G affinity chromatography as was control IgG pooled from ten sera with low levels of aPL. Synaptoneurosomes were purified from perfused rat brain stem. IgG from the patient with the highest level of aPL at a concentration equivalent to 1:5 serum dilution caused significant depolarization of the synaptoneurosomes as determined by accumulation of the lipophylic cation [3H]-tetraphenylphosphonium. IgG from this patient as well as IgG from two elderly patients with high levels of aPL were subsequently shown to permeabilize the synaptosomes to labeled nicotinamide adenine dinucleotide (NAD) and pertussis toxin-ADP-ribose transferase (PTX-A protein) as assayed by labeled ADP-ribosylation of G-proteins in the membranes. No such effects were seen with the control IgG. aPL may thus have the potential to disrupt neuronal function by direct action on nerve terminals. These results may explain some of the non-thromboembolic CNS manifestations of the antiphospholipid syndrome.
Anticardiolipin and anti-β2glycoprotein-I antibodies in patients with systemic lupus erythematosus: Comparison between Colombians and Spaniards
Authors: Cucurull E , Espinoza L R , Mendez E , Molina J F , Molina J , Ordi-Ros J , Gharavi A E
Published: November 2003

We studied the prevalence, isotype distribution, and clinical significance of anticardiolipin (aCL) and anti-β2glycoprotein I (anti-β2) antibodies in two populations of patients with systemic lupus erythematosus (SLE), 160 Colombians and 160 Spaniards. All sera were tested in our laboratory by enzyme-linked immunosorbent assay (ELISA) for IgG, IgM, and IgA aCL, as well as IgG and IgM anti-β2GPI. Positive results for at least 1 of the 3 aCL isotypes were found in 40 Colombians (25%) and 55 Spaniards (34%). IgG aCL was the predominant isotype in both populations. Positive results for at least 1 of the anti-β2GPI isotypes were found in 34 Colombians (21%) and 29 Spaniards (18%). IgG anti-β2GPI was the dominant isotype in Colombians, while IgM was predominant in Spaniards. Positivity for anti-β2GPI in aCL-positive patients was present in 77% in the Colombian group and 50% in the Spaniard group. Among Colombians, IgG aCL and anti-β2GPI correlated with thrombosis, fetal loss, and thrombocytopenia. Among Spaniards, IgG aCL and IgG anti-β2GPI correlated with thrombosis, fetal loss, and livedo reticularis. For detecting thrombosis and fetal loss, aCL ELISA was more sensitive than anti-β2GPI in Spaniards, and anti-β2GPI ELISA was more specific than aCL in both populations.
Primary subcutaneous nocardial infection in a SLE patient
Authors: Balbir-Gurman A , Schapira D , Nahir A M
Published: November 2003

A patient with systemic lupus erythematosus (SLE) developed primary subcutaneous nocardiosis during steroid and cyclophosphamide therapy for diffuse proliferative glomerulonephritis. In spite of local process the patient manifested signs of general deterioration mimicking SLE exacerbation. The diagnosis was made by bacteriologic examination of the material obtained by CT guided aspiration. Surgical drainage and systemic treatment with trimetoprim/sulphamethoxazole (TMT/SMZ) 960 mg twice/d led to a clinical recovery and enabled the continuation of the steroid and cytotoxic regimen.
A double-blind, placebo-controlled, clinical trial of dehydroepiandrosterone in severe systemic lupus erythematosus
Authors: van Vollenhoven R F , Park J L , Genovese M C , West J P , McGuire J L
Published: November 2003

Objective: To determine if dehydroepiandrosterone (DHEA) is beneficial in severe systemic lupus erythematosus (SLE).

Methods: A double-blinded, placebo-controlled, randomized clinical trial in 21 patients with severe and active SLE, manifestated primarily by nephritis, serositis or hematological abnormalities. In addition to conventional treatment with corticosteroids +/-immunosuppressives, patients received DHEA 200 mg/d vs placebo for 6 months, followed by a 6-month open label period. The primary outcome was a prospectively defined responder analysis, based on a quantitatively specified improvement of the principal severe lupus manifestation at 6 months.

Results: Nineteen patients were available for evaluation at 6 months. Baseline imbalance between the groups was noted, with the DHEA group having greater disease activity at baseline (P < 0.05 by physician's global assessment). Eleven patients were responders: 7/9 patients on DHEA vs 4=10 patients on placebo (P < 0.10). Of the secondary outcomes, mean improvement in SLE disease activity index (SLE-DAI) score was greater in the DHEA group (710.3 3.1 vs 73.9 1.4, P < 0.07). Bone mineral density at the lumbo-sacral spine showed significant reduction in the placebo group, but was maintained in the DHEA group.

Conclusion: DHEA therapy, when added to conventional treatment for severe SLE, may at most have a small added benefit with respect to lupus outcomes, but baseline imbalances in the study population limit the generalizability of the results. DHEA appears to have a protective effect with respect to corticosteroid-induced osteopenia in such patients.
Atherosclerosis-related markers in systemic lupus erythematosus patients: The role of humoral immunity in enhanced atherogenesis
Authors: George J , Harats D , Gilburd B , Levy Y , Langevitz P , Shoenfeld Y
Published: November 2003

Systemic Lupus Erythematosus (SLE) patients experience premature atherosclerosis. A deranged lipid metabolism and use of immunosuppressive medications accounts partially for the accelerated process. The role of autoimmunity in atherosclerosis has recently been highlighted. Autoantigenic determinants thought to play a role in the development of atherosclerosis include: modified lipoproteins, heat shock proteins and β2-glycoprotein I (a target of ‘autoimmune’ anticardiolipin antibodies). In this present work we determined autoimmune markers which may be associated with premature atherosclerotic process found in SLE patients. We have found that antibodies to oxLDL were raised in the sera of lupus patients and cross-reacted with cardiolipin and with β2GPI. OxLDL containing immune-complexes of the IgG and IgM isotypes were both elevated in the SLE patients as compared with healthy controls. Patients with high Lipoprotein (a) concentrations (> 30 mg/dl) had higher levels of IgM oxLDL-containing immune-complexes. IgM but not IgG anti-HSP-65 antibodies were elevated in the lupus patients and levels of oxLDL containing immune-complexes correlated positively with the presence of anti-HSP 65 antibodies.

Lysophosphatidylcholine (LPC) is a peroxide-derivative formed during LDL oxidation, was shown to evoke a humoral response in healthy subjects. Antibodies to lysophosphatidylcholine of the IgG but not the IgM isotype were reduced in SLE patients compared with controls, suggesting it may be ‘consumed’ into oxLDL containing immune complexes.

Therefore, SLE patients exhibit a humoral autoimmune response towards the antigenic candidates incriminated in the progression of atherosclerosis. These findings may help identify factors that are involved in accelerating atherogenesis in SLE patients.
Clinical characteristics and outcome of southern Chinese males with systemic lupus erythematosus
Authors: Mok C C , Lau C S , Chan T M , Wong R WS
Published: November 2003

The aims were to study the gender differences in clinical manifestations, disease course and organ damage in systemic lupus erythematosus (SLE).

Clinical manifestations, autoantibody profile, relapses and damage scores were obtained from 51 Chinese males with SLE and compared with 201 consecutive female SLE controls.

Fifty-one males were identified among 630 SLE patients who attended our clinics, giving a male prevalence of 8% and a female to male ratio of 11.4–1. Both the male SLE patients and the female controls had similar age and SLEDAI score at disease onset. Male SLE patients had less alopecia ( P = 0.03), Raynaud's phenomenon ( P = 0.01) and anti-Ro ( P = 0.049) during the course of the disease but none of the differences were statistically significant after correction for multiple observations. The prevalence of major organ involvement in either sex was not different. Both groups of patients had a comparable mean duration of follow-up (104 vs 102 months, P = 0.87). Males had a significantly lower rate of relapses (total No. of flares/patient-year: 0.23 in men vs 0.33 in women, P = 0.04), but the frequency of severe flares (No. of severe flares/patient/year in men 0.08 vs 0.12 in women, P = 0.16) was not significantly different from the females. Male patients with positive anti-Ro had significantly less overall flares than their female counterparts who were anti-Ro positive (0.16 vs 0.34, P = 0.006). However, the use of immunosuppressive agents for disease control in patients of both sexes was similar. 22 (43%) of the males and 78 (39%) of the females had organ damage. A higher percentage of male patients had impairment of renal function ( P = 0.006) but the proportion of patients who required dialysis was not different (4% in men vs 2% in females, P = 0.92). There was also a trend of more cardiovascular damage in the males but the difference was not statistically significant ( P = 0.09). The mean SLICC/ACR scores were not significantly higher in the males than the females (0.71 vs 0.60, P ‘ 0.47).

Males tend to differ from females in clinical manifestations, immunological profile and disease course in SLE. However, there was no gender difference in the involvement of major organs/systems. Males had less overall disease flares than the females but the rate of severe flares was not significantly lower. For patients who were anti-Ro positive, males had significantly less total number of flares/patient-year than their female counterparts. More renal impairment and cardiovascular damage was present in our male lupus patients but the overall damage scores were not significantly higher.
Responsiveness of peripheral blood B cells to recombinant CD40 ligand in patients with systemic lupus erythematosus
Authors: Harigai M , Hara M , Fukasawa C , Nakazawa S , Kawaguchi Y , Kamatani N , Kashiwazaki S
Published: November 2003

Objective: To investigate the immunopathological significance of CD40=CD40 ligand system for B cell hyperactivation in SLE patients, the expression and the function of CD40 on B cells were compared with those of normal controls.

Methods: Expression of CD40 was evaluated by flow cytometry. DNA synthesis of B cells were measured by 3H–TdR incorporation. Antibody production was assessed by ELISA.

Results: There was no significant difference between SLE and normal controls in CD40 expression on peripheral blood B cells. Recombinant CD40 ligand-leucine zipper fusion protein (CD40L-LZ) 3significantly enhanced 3H ÿ TdR incorporation by both SLE and normal B cells–P < 0:01ƒ. H ÿ TdR incorporation of SLE B cells without stimuli (P < 0:001) and with CD40L-LZ stimulation (p < 0:05) were significantly lower in SLE patients compared with normal controls. Active SLE B cells spontaneously produced significantly larger amounts of total IgG than normal B cells (P < 0:05). CD40L-LZ significantly increased the production of total IgG by SLE B cells (P < 0:05), but not by normal B cells. Active SLE B cells spontaneously produced IgG anti-dsDNA and IgG anti-ssDNA antibodies. CD40L-LZ significantly increased the production of these autoantibodies by SLE B cells (P < 0:05). B cells from normal controls do not produce these autoantibodies spontaneously nor in response to CD40L-LZ.

Conclusion: These findings indicate that signalling via CD40 plays an important role in B cell proliferation and autoantibody production in human SLE.
The BH1 idiotype defines a population of anticardiolipin antibodies closely associated with the antiphospholipid syndrome
Authors: Mason A N , Harmer I J , Mageed R A , Mackworth-Young C G
Published: November 2003

Background: A human IgM monoclonal anticardiolipin antibody–BH1–has previously been described, which has characteristics typical of antiphospholipid antibodies in the serum of patients with antiphospholipid syndrome (APS). It appears to be idiotypically distinct from other human monoclonal autoantibodies of different or overlapping ligand-binding specificities derived from patients with related conditions.

Aim: To determine whether the idiotype of BH1 is expressed on particular populations of antibodies (antiphospholipid and anti-β2-glucoprotein I) in the serum of patients with APS and other conditions.

Methods: Sera from patients with APS (9), systemic lupus erythematosus without APS (`uncomplicated SLE'–9), and rheumatoid arthritis (RA–15), and from normal controls (15) were tested by enzyme-linked immunosorbent assay (ELISA) for reactivity with cardiolipin, β2 glycoprotein I (β2 GPI), and a polyclonal anti-idiotype raised against BH1 (RIdBH1). Absorption experiments were subsequently performed on selected sera using micelles of cardiolipin or phosphatidyl choline.

Results: Eight out of nine patients with APS were positive for binding to RIdBH1 (IgG and/or IgM), while only one patient with uncomplicated SLE and none of the patients with RA or the healthy controls were positive. Although all of the patients with APS were positive for binding to β2 GPI, there was poor correlation between these results and levels of binding to cardiolipin and RIdBH1. Absorption of sera from patients with APS by cardolipin micelles resulted in a median reduction in IgG anticardiolipin and anti-β2 GPI activity of 81.6% and 6.3% respectively. For those sera positive for IgG reactivity with RIdBH1 the median reduction in this activity was 79.4%. Antibodies eluted from selected micelles showed activity against cardiolipin, β2 GPI and RIdBH1. Three anticardiolipin-positive sera from patients with RA were similarly absorbed; however the eluted antibodies failed to bind to RIdBH1. Absorption of all these sera with phosphatidyl choline resulted in no significant reduction in any of these activities.

Conclusions: The BH1 idiotype defines a population of serum antibodies associated with features of APS. The antibody response in this condition, though diverse, may include the expression of a restricted group of variable region genes.
Devic's neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus
Authors: Bonnet F , Mercié P , Morlat P , Hocke C , Vergnes C , Ellie E , Viallard J-F , Faure I , Pellegrin J-L , Beylot J , Leng B
Published: November 2003

Neuropsychiatric forms of systemic lupus erythematosus (SLE) vary, most commonly consisting of seizures, psychiatric disturbances, or focal central nervous deficits. This is a new case of neuromyelitis optica or Devic's syndrome during the course of SLE. Few reports of this association exist in the literature. Our objective is to report this unique case of Devic's neuromyelitis optica during pregnancy in a patient with systemic lupus erythematosus. A 28-year-old woman had been diagnosed as having SLE with cutaneous and articular involvement in 1987 when she was 17 years old. She was treated with a synthetic antimalarial agent associated with corticosteroids. In 1994, during the fourth month of pregnancy, she had signs of transverse myelitis with a sensory level at T6 associated with an optic neuropathy suggesting a Devic's syndrome. The patient was managed by plasmapheresis sessions and intravenous corticosteroids. Transverse myelitis recurred postpartum and three years later at the same thoracic level. Management by bolus administration of a steroid and cyclophosphamide resulted in remission again. There have only been around a dozen reports in the literature of patients who had both Devic's neuromyelitis optica and SLE. Magnetic resonance imaging is contributive to diagnosis and therapeutic follow-up, showing spinal cord lesions with increased intensity on T2-weighted sequences. Although the clinical course of the present patient has been favourable so far, the prognosis of this neurologic disease is generally considered to be poor with elevated mortality.
Antibodies to cardiolipin and β2-glycoprotein-1 in HTLV-1-associated myelopathy/tropical spastic paraparesis
Authors: Faghiri Z , Wilson W A , Taheri F , Barton E N , Morgan OStC , Gharavi A E
Published: November 2003

Anticardiolipin and anti-β2GP1 antibodies were measured in 50 patients with HTLV-1-associated Myelopathy-Tropical Spastic Paraparesis (HAM-TSP) and the results were compared with those obtained for 34 HTLV-1-positive and 35 HTLV-1-negative controls, as well as 128 SLE patients. aCL but not anti-β2GP1 was associated with HTLV-1 infection. aCL was more prevalent than anti-β2GP1 (32% vs 8%) and was not associated with anti-β2GP1 in HAM-TSP. IgA was the dominant isotype of aCL and anti-β2GP1. The data suggest that tin HAM-TSP, IgA aCL are frequent and are associated with HTLV-1 infection.
The pulmonary-renal syndrome: a poorly understood clinicopathologic condition
Authors: Bosch X , Font J
Published: November 2003

The co-existence of pulmonary hemorrhage and glomerulonephritis delineates a severe syndrome, often underestimated, resulting from several diseases and frequently associated with serum positivity for antineutrophil cytoplasmic antibodies (ANCA) or antiglomerular basement membrane (GBM) antibodies. The most common illness presenting as pulmonary-renal syndrome is systemic vasculitis. Moreover, the idiopathic pulmonary-renal syndrome is a distinctive clinicopathologic entity with different pathogenetic mechanisms. Tissue immunofluorescence studies are fundamental in distinguishing anti-GBM antibody-mediated forms from immune-complex-mediated and ANCA-associated forms. The type of glomerular or alveolar immunologic injury is the main factor determining the outcome and thus the prognosis of the pulmonary-renal syndrome. Development and improvement of appropriate serologic detection techniques have given reliable and early guidance for diagnosing these cases.
Treatment of chronic bilateral pleural effusions with intravenous immunoglobulin and cyclosporin
Authors: Sherer Y , Langevitz P , Levy Y , Fabrizzi F , Shoenfeld Y
Published: November 2003

A 48 y old woman with unremarkable medical history was admitted with bilateral pleural effusions; even though the fluid was drained, it re-accumulated and necessitated many repeated drainages in the following 2.5 y (56 hospitalisations). The patient underwent an extensive diagnostic work-up that disclosed elevated serum antinuclear antibodies, serum anti-dsDNA antibodies, pleural fluid anti-dsDNA and decreased pleural fluid C3 and C4. During that period she has been treated with a variety of immunomodulating agents, several pleural talcage and pleurectomy, without any apparent response. Thereafter, she received six courses of IVIg (2 g/kg body weight) in monthly intervals, followed by four months treatment with cyclosporin. This treatment resulted in gradual and eventually complete disappearance of the pleural effusion, and now after more than 2 y the patient is free of symptoms and receives no further medications.
Immunological and clinical differences between juvenile and adult onset of systemic lupus erythematosus
Authors: Carreño L , López-Longo F J , Monteagudo I , Rodríguez-Mahou M , Bascones M , González C M , Saint-Cyr C , Lapointe N
Published: November 2003

Introduction: Systemic lupus erythematosus (SLE) in children usually follows a more severe course than in adults, but sometimes in the previous studies reported there are many confounding factors

Objective: To analyse the immunological and clinical characteristics of SLE juvenile onset and SLE adult onset.

Methods: We studied 179 patients with SLE, 49 patients were aged 6 – 18 yrs at onset of disease. Anti-dsDNA antibodies were detected by radioimmunoassay and antibodies to extractable nuclear antigens (ENA): anti-nRNP, anti-Sm, anti-Ro/SS-A and anti-La/SS-B antibodies by ELISA, counterimmuno-electrophoresis and immunoblotting.

Results: Juvenile-onset SLE shows a higher frequency of cutaneous vasculitis (44.8% vs 27.6%; P < 0.05), seizures (18.3% vs 7.6%; P < 0.05) nephropathy (67.3% vs 48.4%; P < 0.025), and discoid lupus erythematosus (26.5% vs 13.8%; P < 0.05). The incidence of articular manifestations is lower than in adults (85.7% vs 96.1%; P < 0.025). No significant differences were found between the two groups in relation with the prevalence of antinuclear antibodies.

Conclusions: Juvenile-onset SLE has more frequent neurological and renal manifestations than adult-onset SLE, but immunological markers are similar in both groups. These features suggest the most severe clinical manifestations in the juvenile-onset SLE group are not related with the presence of studied antibodies by different methods.
Antiphospholipid (Hughes') syndrome in African-Americans: IgA aCL and aβ2 glycoprotein-I is the most frequent isotype
Authors: Diri E , Cucurull E , Gharavi A E , Kapoor D , Mendez E A , Scopelitis E , Wilson W A
Published: November 2003

Antiphospholipid (Hughes') syndrome (APS) has not been reported in African-Americans (A-A) as frequently as in other ethnic groups. We describe eight A-A female patients with APS, including two cases of primary APS (PAPS), four with APS secondary to systemic lupus erythematosus (SLE), one with Sjögren's syndrome, and one with overlap connective tissue disease (CTD). Their mean age was 34 y (range 24–47 y). Patients were followed for a mean of 6 y (range 0.3–11 y). During follow up, both anticardiolipin (aCL) and anti-b2glycoprotein-I (ab2GPI) antibodies were measured in stored sera by enzyme-linked immunosorbent assay (ELISA). IgA was the most frequent isotype of aCL and ab2GPI, and co-occurred with the IgM isotype in three of four patients with neurologic manifestations.
Human Fc gamma receptor IIA (FcγRIIA) genotyping and association with systemic lupus erythematosus (SLE) in Chinese and Malays in Malaysia
Authors: Yap S N , Phipps M E , Manivasagar M , Tan S Y , Bosco J J
Published: November 2003

SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcγRIIA) occurs in two allelic forms. The allele FcγRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcγRIIA-H131 has a higher capacity for hIgG2 compared to FcγRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcγRIIA using a novel polymerase chain reaction-allele specific primer(PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (w2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcγRIIA-H131 in the ethnic groups studied.
Control of severe systemic lupus erythematosus after high-dose immunusuppressive therapy and transplantation of CD34+ purified autologous stem cells from peripheral blood
Authors: Fouillard L , Gorin N C , Laporte J Ph , Leon A , Brantus J F , Miossec P
Published: November 2003

A 35 y old woman with severe and progressive systemic lupus erythematosus (SLE) received highdose chemotherapy followed by a T cell depleted autologous stem cell transplantation. Peripheral blood stem cell were mobilised with Cyclophosphamide 4.5 g/m2 followed by Granulocyte-Colony Stimulating Factor (G-CSF). A CD34 positive selection provided a 3 log T cell depletion. High-dose immunosuppression consisted of the BEAM regimen. The purified autograft was reinfused on day 0. In the post transplant period, hemopoietic growth factors, G-CSF, Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Erythropoietin, were administered, engraftment was rapid. Both the mobilisation and the transplant procedures were easily performed and well tolerated. One year later, the patient is in clinical remission. The ANA and anti-SSA-antibodies were undetectable at 1 and 6 months after intensification, but reappeared at low levels at 9 months. Corticosteroid requirement has gradually decreased. In conclusion, we report here the favourable evolution of a patient with a severe SLE, who clinically improved with high-dose immunosuppressive therapy and autologous stem cell transplantation, and showed a 9 month serological remission.
Classification and definition of major flares in SLE clinical trials
Authors: Petri Michelle , Buyon Jill , Kim Mimi
Published: November 2003

Multiple reliable and valid disease activities indices exist and have been used successfully in longitudinal studies. However, the definition of flare, using these intruments, has not been universally decided or accepted. Because flare is one of the three major patterns of lupus activity, it will remain an important outcome measure in both longitudinal and clinical trial studies.
Equivalence trials in SLE research: issues to consider
Authors: Kim Mimi Y , Buyon Jill P , Petri Michelle , Skovron Mary Louise , Shore Roy E
Published: November 2003

In contrast to the objective of most clinical trials, which is to demonstrate superiority of an experimental treatment over a standard or placebo, the aim of an equivalence trial is to show that two treatments are equivalent in outcome or only marginally different. This would be of interest when an experimental treatment offers advantages such as reduced toxicity, ease of administration, or cost relative to the standard. Demonstrating equivalence may also be a goal when evaluating the safety of certain drugs because similarity in the risks of an adverse event in subjects exposed and unexposed to the drug is an indication of its safety. The classical formulation of the null hypothesis of treatment equality that is used in superiority trials is not applicable to equivalence trials because absolute equivalence between treatment groups cannot be proven. The strategy in equivalence trials is to define a maximum difference between treatment groups that is clinically acceptable and then assess whether there is sufficient evidence from the trial to conclude that the true treatment difference is within this acceptable range. In this paper, we discuss issues surrounding the planning, conduct, and analysis of equivalence trials in the context of SLE, with examples from the SELENA study.