bluuebunny/crossref_metadata_2025 huggingface dataset:
Coexistence of lupus anticoagulant and acquired haemophilia in a patient with monoclonal gammopathy of unknown significance
Authors: Taher A , Abiad R , Uthman I
Published: November 2003

Acquired haemophilia or factor VIII (FVIII) deficiency, caused by FVIII inhibitorantibodies, is a very rare condition that commonly results in severe haemorrhagic complications. We report a case of acquired haemophilia presenting with a left calf nontraumatichaematoma. The patient was also found to have lupus anticoagulant (LAC). The simultaneous presence of LAC and FVIII inhibitor is exceedingly rare. The differentiationbetween these two conditions is crucial, because both result in a prolongationof the activated partial thromboplastintime test, which does not correct when mixed with the plasma of a normal control; however, the clinical manifestations range from thrombosis in the presence of LAC to massive haemorrhage with FVIII inhibitors.
Abnormal expression of chemokine receptors on T-cells from patients with systemic lupus erythematosus
Authors: Eriksson C , Eneslätt K , Ivanoff J , Rantapää-Dahlqvist S , Sundqvist K-G
Published: November 2003

The expressionof chemokinereceptors on T-cells and chemokinelevels in the blood was studied in 23 patients with SLE (ACR criteria), seven patients with rheumatoid arthritis (RA) and in 15 healthy controls using flow cytometry, RT-PCR and ELISA. The cell surface expression of the chemokine receptors CXCR5 and CCR6 was decreased in SLE patients compared with controls (P 0.051 and P 0.002, respectively). The decrease of CXCR5 was confined to SLE patients with inactive disease (SLEDAI < 6) compared with active disease (SLEDAI ≥6) and controls. CXCR2 and CCR1 were increased in patients with active SLE compared with patients with inactive disease (P 0.001 and P 0.01, respectively) and with controls (P 0.02 and P 0.053, respectively). The levels of the chemokines MIP-1b MCP-1, SDF-1a, IP-10 and RANTES were significantly elevated in SLE patients compared with controls. Patients with renal involvement had increased surface expression of CXCR3 and CCR3 (P 0.04 in both) and a lower level of soluble IP-10 compared with patients without renal disease (P 0.025) and compared with controls (P 0.001). The ratio between CCR5 and CCR3 was significantly increased in RA patients compared with SLE patients and controls supporting a Th1 overweight in RA. In conclusion, patients with SLE showed abnormal T-cell expression of several chemokine receptors and levels of soluble chemokines in their plasma/serum.
Left-sided heart valve abnormalities and risk of ischemic cerebrovascular accidents in patients with systemic lupus erythematosus
Authors: Morelli S , Bernardo M L , Viganego F , Sgreccia A , De Marzio P , Conti F , Priori R , Valesini G
Published: November 2003

The aim of the study was to assess the relationship between ischemic cerebrovascular accidents (ICVAs), that is, transient ischemic attack (TIA) or stroke, and left-sided heart valve abnormalities (LHVAs) in patients with systemic lupus erythematosus (SLE). In total, 71 consecutive SLE patients were studied.At baseline, history, clinical and laboratoryevaluations, as well as trans-thoracic echocardiography (TTE) were performed. From the original population, so patients were followed up for a mean time of 5.80 + 1.53 years. After a mean period of 5.39 + 1.42 years; 40 patients underwent a repeat TTE.

Previous ICVA history was present at baseline in 16 patients (22.5%). Of these, 13 (81.2%) had evidence of LHVAs on TTE. Previous ICVAs were significantly associated to diagnosis of secondary anti-phospholipid syndrome (SAPS), positivity for anti-cardiolipin antibodies (aCl), and LHVAs. Multivariate analysis confirmed the correlation between previous ICVAs and LHVAs. LHVAs were not more commonly observed in patients with SAPS compared to patients without SAPS. At the end of follow-up, irrespective of any differences in antithrombotic treatment, ICVAs had occurred in 13 patients.During follow-up, ICVAs had recurredin seven patients, while a first eventTIA occurredin one patient. Multivariate analysis confirmed the relationship between ICVAs and LHVAs, and a trend towards a positive correlation of the former with SAPS. This study demonstratesthat LHVAs represent a compelling risk factor for the development of ICVAs in SLE patients. Conversely, SAPS and aCl positivity, although associated with ICVAs, did not clearly correlate with LHVAs in our study. These results provide insight on the pathogenesis of ICVAs and may give clues on the potential efficacy of preventive/therapeutic strategies in different SLE subpopulations.
Cerebral hypoperfusion detected by SPECT in patients with systemic lupus erythematosus is related to clinical activity and cumulative tissue damage
Authors: López-Longo F J , Caro N , Almoguera M I , Olazarán J , Alonso-Farto J C , Ortega A , Monteagudo I , González C Manuel , Carreño L
Published: November 2003

Cerebral single-photon emission computed tomography (SPECT) is a sensitive technique for the detection of central nervous system (CNS) involvement in systemic lupus erythematosus (SLE). The objectivewas to determine whether a relationship exists between cerebral hypoperfusionas detected by cerebral SPECT, cumulative tissue damage and the clinical activity of SLE. Cerebral technetium-99m-L, L-ethyl cysteinate dimer (99mTc-ECD) SPECT was performed in two groups of patients: 10 women with SLE (Group A) who had no previous history of major neuropsychiatric(NPS) manifestations and no minor NPS symptoms in the last six months, and 57 unselected women with SLE (Group B). In the same week that SPECT was performed, the SLE disease activity index (SLEDAI), SLICC/ACR damage index, native anti-DNA antibodies (ELISA) and erythrocyte sedimentation rate (ESR) were determined. In Group A, cerebral SPECT showed moderate or severe hypoperfusion (abnormal SPECT) in five patients without NPS symptoms, unrelated to age (mean 24.8 versus 27.8 years) or disease duration (mean 6.8 versus 9 years). Patients with significant cerebral hypoperfusionhad greater clinical disease activity (mean SLEDAI 13.6 versus 7.6) (SLEDAI > 7 in 5/5 versus 1/5; Fisher: 0.023; OR: 33; 95% CI: 2.3-469.8) and ESR (mean 43.6 versus 9.8; P < 0.05). In Group B, the mean age of the 57 unselectedwomen with SLE was 37 years (SD 6.3) and the mean duration of the disease was 9.7 years (SD 6.3). Cerebral SPECT revealed normal perfusion or mild hypoperfusion (normal SPECT) in 30 patients (52.6%), and moderate or severe hypoperfusion in 27 (47.4%). Hypoperfusion was unrelated to age, duration of SLE or concentrations of anti-DNA antibodies and C3 and C4 fractions. Patients with significant cerebral hypoperfusion had more active clinical disease (mean SLEDAI 13.92; SD 8.44 versus 4.56; SD 4.15) (Mann-Whitney, P < 0.005), more cumulative tissue damage (mean SLICC 2.66; SD 2.84 versus 1.03; SD 1.51) (Mann-Whitney, P 0.035), and higher ESR values (mean 28.7; SD 22.5 versus 17.7; SD 13.3) (Mann-Whitney, P 0.023) than patients with normal SPECT studies. Significant cerebral hypoperfusion was related both to NPS manifestations present at the time of the study (17 of 27, 63% versus 3 of 30, 10%) (OR: 15.3) and cumulative manifestations (19 of 27, 70.4% versus 8 of 30, 26.7%) (OR: 6.5), whether mild (OR: 5.5) or severe (OR: 8.2). In conclusion, cerebral hypoperfusion detected by SPECT in patients with SLE is related to clinical activity (SLEDAI), cumulative tissue damage (SLICC) and concomitant or previous NPS manifestations.
Antiphospholipid antibodies and antiphospholipid syndrome in 57 children and adolescents with systemic lupus erythematosus
Authors: Campos L MA , Kiss M H , D’Amico É A , Silva C A Almeida
Published: November 2003

The presence of antiphospholipid (aPL) antibodies and antiphospholipid syndrome (APS) was researchedin 57 childrenand adolescentswith systemic lupus erythematosus(SLE). The frequencyof aPL antibodies was 75.4% (anticardiolipin70.2% and lupus anticoagulant29.1%). The positivity for these antibodies fluctuated during the course of the disease. No association was found between aPL antibodiesand clinical or laboratory manifestationsor the autoantibodiesstudied, nor with the activity or gravity of the SLE. APS was diagnosed in 14% of the cases (eight patients), on average three years after the diagnosis of SLE. Four patients had arterial thrombosis (stroke, three; transient ischaemic attack, one; amaurosis fugax, two; renal, one), one presented with deep vein thrombosis (DVT) and three had involvement of small calibre vessels (osteonecrosis, two; transverse myelitis, one). Recurrences were observed in three of the eight cases (37.5%), with a mean interval of 13 months between the events. The presence of APS was associated with haemolytic anaemia, leukopenia, thrombocytopenia, coagulation abnormalities, ischaemic cerebrovascularaccidents, amaurosis fugax, osteonecrosisand interstitial pneumonitis. A negative association was observed between APS and the presence of anti-Ro antibodies.
The heterogeneity of neuropsychiatric systemic lupus erythematosus is reflected in lack of association with cerebrospinal fluid cytokine profiles
Authors: Jönsen A , Bengtsson A A , Nived O , Ryberg B , Truedsson L , Rönnblom L , Alm G V , Sturfelt G
Published: November 2003

The objectivewas to study the occurrenceof autoantibodiesand cytokinesin serum and cerebrospinal fluid (CSF) in neuropsychiatric systemic lupus erythematosus (NPSLE). In total, 28 consecutive patients with NPSLE and 16 systemic lupus erythematosus (SLE) patients without neuropsychiatric involvement (non-NPSLE) were studied. IFN-a, IL-6, IL-10, soluble terminal complement complex (TCC), anti-ribosomal P protein antibodies (anti-P) and anti-cardiolipin antibodies (aCL) were measured in serum and CSF by immunoassays. Analyses of white blood cell differential count, CSF-albumin/serum-albumin ratio, IgG-index in CSF and isoelectric focusing in serum and CSF were also performed. CSF specimens from 23 healthy individuals were used as controls. IFN-a was elevated in the CSF of 5 of 28 NPSLE patients compared to three of 14 among the non-NPSLE patients. IL-6 was elevated in CSF in three of 26 NPSLE patients. Normal concentration of IL-10 was found in CSF in all 27 NPSLE-patients analysed. IFN-a in serum was elevated in 18 of 28 NPSLE patients. No distinct clinical phenotype was related to elevated cytokine concentration in serum or CSF. One patient with cerebral involvement complicated by progressive multifocal leukoencephalopathy displayed a very high IFN-a concentration in serum. High concentration of TCC was present in CSF from only one patient with systemic vasculitis and focal cerebral symptoms. In conclusion, the results of this study suggest that the diagnostic value of serum and CSF concentrationsof IFN-a, IL-10, IL-6 and TCC is limited in unselected neuropsychiatricSLE, probably due to the heterogeneityof NPSLE pathogenesis.
Poor prognosis of end-stage renal disease in systemic lupus erythematosus: a cohort of Chinese patients
Authors: Lee Po-Tsang , Fang Hua-Chang , Chen Chien-Liang , Chiou Yee-Hsuan , Chou Kang-Ju , Chung Hsiao-Min
Published: November 2003

We studied the clinical course of 26 systemic lupus erythematosus(SLE) patients who started regular dialysis at our hospital and whose stay exceeded a three-month duration in order to investigate the long-term prognosis in a Chinese cohort. Clinical and serological activities of lupus before and after dialysis were analysed. To compare the long-term survival rate, controls were set using 78 age-matched end-stage renal disease (ESRD) patients who did not have SLE or diabetes mellitus and entered the chronic dialysis program at a similar period with SLE dialysis patients. There was a significant decrease in clinical lupus activity after starting regular dialysis (P < 0.05); however, the serologicalactivity remained the same. The five-and ten-yearsurvivalrates were significantly lower in the SLE patients (73 and 38% in the SLE group versus 95 and 88% in the non-SLE group, P < 0.05). SLE patients had a 4.3-times higher risk of death than non-SLE patients (P < 0.05, 95% confidence interval,1.2-15.2). Also, the deceased SLE patients had persistent lower serum levels of complement 3. SLE patients with ESRD remain clinically quiescent despite persistent serological abnormalities and have a worse prognosis than other uremia patients in the Chinese population.
Synthetic CpG oligodeoxynucleotides accelerate the development of lupus nephritis during preactive phase in NZB ×NZWF1 mice
Authors: Hasegawa K , Hayashi T
Published: November 2003

The effect of synthetic CpG-oligodeoxynucleotides (CpG-ODN) on the development of lupus nephritis during preactive phase (within seven months of age) in autoimmune lupus NZB ×NZWF1(B/WF1) mice was examined. Treatment of CpG-ODN was started at the age of 2.75 months and continued until 6.25 months. Overt disease began at the age of six months and progressed linearly at the age of 6.75 months in CpG-ODN-treated, but not control ODN-treated (control) groups. Also compared to control group, CpG-ODN-treated mice exhibited a severe glomerulonephritis(GN), with prominent deposits of IgG2a and C3, which paralleled increased titre of IgG2a type anti-nuclear antibody in the blood. Among several cytokines (interleukin, IL-6, IL-4, IL-1a, IL-10, interferon-g and tumor necrosis factor-a) in blood, IL-6 production paralleled the developmentof lupus nephritis. The present study suggests that CpG-ODN may enhance IL-6 production. The role of IL-6 in the development of GN will be discussed.
Recurrent cerebral infarctions in polyarteritis nodosa with circulating antiphospholipid antibodies and mitral valve disease
Authors: Morelli S , Perrone C , Paroli M
Published: November 2003

A case of recurrent cerebral infarctions in a 42-year-old woman affected by polyarteritis nodosa and antiphospholipid syndrome is reported. Two-dimensional echocardiography revealed grossly thickened mitral valve leaflets, possibly related to the presence of antiphospholipid antibodies. Thus, an embolic source at mitral level is hypothesized.
Effect of 1 year cyclosporine a treatment on the activity and renal involvement of systemic lupus erythematosus: a pilot study
Authors: Dostál C , Tesař V , Rychlík I , Zabka J , Vencovskŷ J , Bartûňková J , Stejskalová A , Tegzova D
Published: November 2003

Our objective was to determine the effect of 1 year low-dose cyclosporine A (CSA) treatment on disease activity and renal involvement in systemic lupus erythematosus (SLE). Patients included in the pilot study had an active form of the disease as defined by the SLE Disease Activity Index (SLEDAI). Main organ involvement was represented by lupus nephritis classified in repeated renal biopsies. Eleven patients with SLE were enrolled in the study. In eight of them, previous therapy with cyclophosphamide or azathioprine had to be interrupted due to serious adverse reaction or low efficacy. Nine patients experienced clinical nephrotic syndrome, and two the nephritic syndrome. After 12 months of CSA treatment, the mean SLEDAI score had decreased significantly from 26.18 to 4.00 (P < 0.01). Similarly, the titre of antinuclear and anti-dsDNA antibodies had dropped significantly (P < 0.01). Proteinuria decreased rapidly from 9.10 to 1.70 g/24 h (P < 0.001). According to the WHO classification of renal biopsies, three patients had their class altered from IV to III in response to CSA treatment and five patients had changed the status from the high severity grade to the mild. The adverse reactions included hypertension (45%), gingival hyperplasia (18%) and hirsutism (9%). No significant increase in serum creatinine or any CSA related toxic changes were found in renal biopsies. The favourable response observed in patients with active SLE and with major renal involvement strongly suggests that low-dose CSA is a potent drug as much for the reduction of the disease activity as for lupus nephropathy treatment.
Clinical profile of patients with late-onset SLE: not a benign subgroup
Authors: Mak S K , Lam E KM , Wong A KM
Published: November 2003

The onset of systemic lupus erythematosus (SLE) in later life has been associated with a benign clinical course and better prognosis compared with those with earlier onset. However, different reported studies have failed to agree on a distinct pattern of presentation. We retrospectively studied the clinical profile of a predominantly Chinese lupus population to review the behaviour of lateonset patients. Cumulative clinical features and laboratory findings in 102 patients with SLE were collected. Late-onset patients tended to have a less marked female predominance, a more insidious onset at presentation ( P < 0.001), a decreased incidence of cutaneous lesions ( P < 0.05), an increased occurrence of serositis ( P = 0.004) and a lower cumulative number of SLE manifestations (P = 0.022) compared with the early-onset group. The incidences of all major organ involvement as well as the requirement of immunosuppressive therapies were similar in the two groups. Thus, in this study, late-onset SLE patients had a different clinical profile from the early-onset group, but did not constitute a benign subgroup of the lupus population.
Association of osteonecrosis in systemic lupus erythematosus with abnormalities of fibrinolysis
Authors: Sheikh J S , Retzinger G S , Hess E V
Published: November 2003

Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing osteonecrosis (ON). Twenty-six patients with SLE were studied. Fifteen of these had ON and 11 did not. The latter were used as control subjects. Various coagulation analytes including antithrombin III (ATIII) activity, protein C activity, protein S activity, a2-antiplasmin activity, anticardiolipin antibodies (aCL), plasminogen activator inhibitor (PAI-1) activity and tissue type plasminogen activator (tPA) antigen were measured using citrated plasma samples from the patients. A significant proportion (80%) of patients had at least one laboratory abnormality that has been associated with a thrombotic predisposition. ON was significantly associated with elevated levels of PAI-1 activity; it was also associated with elevated PAI-1/tPA ratio. There was no association between ON of SLE and abnormalities of the other measured coagulation analytes. These results suggest that defective fibrinolysis seems to be operative in the pathogenesis of ON associated with SLE. The defect appears to involve an imbalance between tPA and its inhibitor, PAI-1. This imbalance could represent an important risk factor in the pathogenesis of ON.
Two populations of endothelial cell antibodies cross-react with heparin
Authors: Renaudineau Y , Revelen R , Bordron A , Mottier D , Youinou P , Le Corre R
Published: November 2003

As endothelial cells (EC) express heparin-like glycosaminoglycans, such as heparan sulfate, it was essential to investigate the relation of anti-EC antibody (AECA) to heparin reactivity. AECA were detected in 43 of 131 autoimmune sera and anti-heparin antibodies (AHA) in 25. These autoimmune reactivities were significantly associated (P corrected < 0.0005). Seven AECA-positive/AHA-positive and three AECA-negative/AHA-positive sera were affinity-purified using protein G column followed by a heparin-Sepharose column. Two populations of AECA were recovered from the second column. One was eluted with 0.4 M NaCl which bound to EC and to solid-phase heparin with low affinity, but not to soluble heparin. The second population of AECA, which was eluted with 4 M guanidine HCl=2 M NaCl, recognized EC and solid-phase heparin with high affinity, but also soluble heparin. The latter population of AECA might thus be an important cause of autoimmune vascular thrombosis in systemic diseases.
A Long-Term Study of Hydroxychloroquine Withdrawal on Exacerbations in Systemic Lupus Erythematosus
Authors:   The Canadian Hydroxychloroquine Study Group, Tsakonas E , Joseph L , Esdaile J M , Choquette D , Senécal J-L , Cividino A , Danoff D , Osterland C K , Yeadon C , Smith C D
Published: November 2003

The ability of antimalarials to moderate severe disease activity in systemic lupus erythematosus (SLE) is plausible but undemonstrated. We evaluated the long-term effectiveness of maintaining treatment with hydroxychloroquine sulphate (HCQ) to prevent major flares in quiescent SLE. Forty-seven patients with quiescent SLE who had been randomized to take HCQ (n = 25) or placebo (n = 22) as part of a 24-week withdrawal trial were evaluated for an additional 3 years. The primary outcome was time to a major flare of SLE which resulted in either the institution of or an increase in the current dosage of prednisone of 10 mg/day or more, or institution of therapy with immunosuppressive agents. Secondary outcomes included the specific subtype of these major flares (glomerulonephritis, vasculitis or other) and hospitalization for an exacerbation of SLE. An intent-to-treat analysis was conducted.

Over the 42 months of study, 11 of 22 (50%) patients randomized initially to placebo, and seven of 25 (28%) patients randomized to continue treatment experienced a major flare. The relative risk of major flare for those randomized to continue HCQ compared with controls was 0.43 (95% CI: 0.17, 1.12). The relative risks for subtypes of flares were 0.26 (95% CI: 0.03, 2.54) for nephritis, 0.51 (95% CI: 0.09, 3.08) for vasculitis and 0.65 (95% CI: 0.17, 2.41) for flares characterized by other symptoms. The relative risk of hospitalization for major flare for patients randomized to continue hydroxychloroquine was 0.58 (95% CI: 0.13, 2.60). While the results are not statistically significant, they are compatible with the clinical belief that HCQ has a long-term protective effect against major disease flares in SLE and suggest that on average, HCQ use reduces major flares by 57% (95% CI: 83% reduction to 12% increase).
Undifferentiated connective tissue diseases: the clinical and serological profiles of 91 patients followed for at least 1 year
Authors: Mosca M , Tavoni A , Neri R , Bencivelli W , Bombardieri S
Published: November 2003

The objective of this work was to evaluate the clinical and serological profiles of patients with undifferentiated connective tissue diseases (UCTD) who had been followed for at least 1 year. The retrospective analysis (1974–95) was based on UCTD patients diagnosed on the basis of clinical manifestations suggestive of a connective tissue disease, and the presence of at least one non-organspecific autoantibody. A total of 91 patients were evaluated. The condition of 79 remained stable during the follow up, while in 12 the UCTD evolved to systemic lupus erythematosus (SLE) within a mean period of 3 years (min. 1 year, max. 8 years, median 2 years) after the onset of the disease. At baseline none of the variables, considered alone, showed an association with the future development of SLE. Multiple regression analysis, however, suggested that the association of sicca symptoms, Raynaud's phenomenon and/or photosensitivity was inversely correlated with the development of SLE ( P = 0.0012, Fisher's exact test). The most common clinical manifestations of UCTD included arthritis, arthralgias, Raynaud's phenomenon, xerostomia, xerophthalmia and leukopenia. The stable UCTD patients showed a simple autoantibody profile characterized by a single autoantibody specificity in 82% of the cases 30% with anti-Ro/SSA alone and 28% with anti-RNP alone. This profile remained stable during the follow up. Anti-RNP antibodies alone correlated with the presence of Raynaud's phenomenon and arthritis ( P < 0.001 and P < 0.01, respectively), while anti-Ro/SSA antibodies alone correlated with xerostomia and xerophthalmia ( P < 0.01). In conclusion, the UCTDs in most of our patients seem to represent distinct clinical entities with a limited autoimmune repertoire rather than the early phases of definite connective tissue diseases. They could therefore provide an ideal model for the study of the clinico-serological correlations in autoimmune diseases.
Neuropsychiatric systemic lupus erythematosus before and after immunosuppressive treatment: a FDG PET study
Authors: Otte A , Weiner S M , Hoegerle S , Wolf R , Juengling F D , Peter H H , Nitzsche E U
Published: November 2003

At its inception, morphological imaging, like magnetic resonance imaging (MRI), is often not useful in neuropsychiatric systemic lupus erythematosus (NPSLE), although the disease clinically shows cerebral symptoms. Functional imaging, like positron emission tomography (PET), may be a method that offers some advantages. We report a 53-year-old white man with decreased memory and visual disturbances who met four of the American Rheumatism Association (ARA) criteria for the classification of SLE. He was investigated before and after 3 months of therapy using PET and F-18-fluoro-2-deoxy-D-glucose (FDG). Treatment consisted of prednisone (25 mg/day, tapered to 10 mg/day) and cyclophosphamide (daily 100 mg for 3 weeks followed by a drug-free interval of 1 week). For the control group, 15 clinically and neurologically healthy volunteers (5 male, 10 female, aged 48–7 years) were investigated. All study participants additionally had a cranial MRI. In both controls and the SLE patient, cranial MRI was negative. However, the patient showed a significant hypometabolism in the region parieto-occipital on both sides and the parietal region on the right side before treatment. After treatment metabolism in these regions was within normal limits. Hence, FDG-PET could help to verify brain-onset of SLE earlier and may be a powerful tool for controlling SLE treatment.
High levels of circulating early apoptic peripheral blood mononuclear cells in systemic lupus erythematosus
Authors: Perniok A , Wedekind F , Herrmann M , Specker C , Schneider M
Published: November 2003

Increased in vitro apoptosis and altered expression of apoptosis-related molecules have been reported in systemic lupus erythematosus (SLE). It was speculated that autoantigens released from apoptizing cells may contribute to the etiopathogenesis of SLE by both activation of autoreactive lymphocytes and the formation of immune complexes. Conflicting data about the level of cellular apoptosis from animal models for SLE and human SLE indicate different pathomechanisms.

In the present study we analysed the count of circulating early apoptotic cells and its correlation with the clinical activity in SLE compared with the amount in primary systemic vasculitis (PSV). The percentage of early apoptotic cells determined by Annexin V-FITC binding cells was significantly increased in peripheral blood of SLE patients compared with normal healthy donors (NHD) and PSV (NHD 5.62%, SLE 13.68%, PSV 8.69%). Analysis of lymphocytes revealed significantly increased counts in the T cell populations (NHD 5.15%, SLE 12.22%, PSV 10.01%), whereas the increase in B cells did not reach significance level (NHD 9.20%, SLE 18.95%, PSV 16.59%). Apoptotic cell count revealed no correlation to SLAM-Score or to immunosuppressive therapy, corticosteroid-dosage or absolute lymphocyte count.

The general increase of circulating apoptotic cells may indicate an impaired clearance in SLE patients, independent of clinical activity or therapeutic interventions. Autoantigens from apoptotic cells may contribute to both activation of autoreactive lymphocytes and formation of immune complexes.
Enhancement of hydroxyl radical DNA cleavage by serum anti-dsDNA antibodies in SLE
Authors: Watanabe N , Kubota T , Miyasaka N , Kanai Y
Published: November 2003

Autoantibodies reactive with double-stranded (ds) DNA are a hallmark of systemic lupus erythematosus (SLE), but it is not fully elucidated how these antibodies contribute to the various pathological changes observed in lupus patients. In a previous study, we have found a significant enhancement effect of two murine monoclonal anti-dsDNA antibodies on DNA cleavage by the hydroxyl radical. We have extended this study and have found that purified polyclonal anti-dsDNA antibodies from sera of lupus patients and an MRL/ lpr mouse, but not anti-ssDNA antibodies, also enhanced radical cleavage of DNA. The cleavage was inhibited by EDTA, DMSO and thiourea. The antibody preparations per se did not cleave DNA. These results suggest that such an enhancement effect on DNA cleavage is a feature of a significant part of anti-dsDNA antibody population and a possible clue in understanding the roles of anti-dsDNA antibodies in the pathophysiology of SLE under certain circumstances.
Measurement of damage in 210 Mexican patients with systemic lupus erythematosus: relationship with disease duration
Authors: Zonana-Nacach A , Camargo-Coronel A , Yáñez P , de Lourdes Sánchez M , Jáimenez-Balderas F J , Aceves-Avila J , Martínez-Osuna P , Fuentes J , Medina F , Fraga A
Published: November 2003

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index is a validated instrument specifically designed to ascertain damage in SLE; this instrument has been applied mainly to Caucasians and African-American SLE patients. The objective of this study was to assess damage using the SLICC/ACR Damage Index in Mexican SLE patients. The SLICC/ACR Damage Index was applied to 210 consecutive SLE patients with disease of variable duration. The SLICC/ACR Damage Index was assessed by review of hospital clinical records, interview and physical examination. One hundred and seventeen (55.5%) patients had some damage. The proportion of patients with damage increased significantly with disease duration (33% at 1–60 months, 66% at 61–120 months and 70% at ≥121 months, P < 0.001). The main organ systems involved were musculoskeletal (osteonecrosis), neuropsychiatric (neuropathy, seizures), gonadal (amenorrhea prior to age 40 years), ocular (cataracts), renal (glomerular filtration < 50%) and peripheral vascular (permanent damage by venous thrombosis). Damage was frequent, increased over time, particularly for ocular, renal, musculoskeletal and gonadal. Patients who experienced damage were older, had a longer disease duration, a greater number of ACR criteria at diagnosis, and were more likely to have renal involvement and antibodies to dsDNA. The damage occurred in many different domains and started to develop early after disease onset. Mexican patients had more peripheral vascular and gonadal involvement compared with published data from non-Hispanic SLE populations.
Cerebral magnetic resonance imaging in patients with or without antiphospholipid antibodies
Authors: Hachulla E , Michon-Pasturel U , Leys D , Pruvo J-P , Queyrel V , Masy E , Arvieux J , Caron C , Brevet-Coupeé F , Hatron P-Y , Devulder B
Published: November 2003

Objective: To determine in patients with systemic lupus erythematosus (SLE) or with primary antiphospholipid syndrome (PAPS) the prevalence of cerebral magnetic resonance imaging changes (MRI) and the relationship with antiphospholipid antibodies.

Methods: Twenty-nine consecutive SLE patients, 24 PAPS patients and 31 healthy controls were prospectively included in the study and underwent MRI Scan over a 1-year period. MRI scans were analyzed separately by a neuroradiologist for white matter changes [periventricular hyperintensity (PVH) (0–6 scale), deep white matter hyperintensity (WMH) (0–24 scale)], and one neurologist for cerebral atrophy (0–39 scale) and stroke subtypes. Statistical assessment consisted of a discriminant analysis performed with SAS-package with MRI data as dependent variables and, as independent variables, age, sex, arterial hypertension, diabetes mellitus, cardiopathy, migraine, neurological symptoms, antiphospholipid antibodies, SLE, steroid treatment.

Results: The prevalence of cerebral atrophy was increased in both SLE and PAPS groups relative to controls. PVH and WMH scores were significantly higher in SLE and PAPS than in controls. Focal infarct did not differ in the SLE group when compared with PAPS. PVH and WMH scores were significantly higher in patients with neurological symptoms. Using a correlation test we found a weak significant correlation between cerebral atrophy and lupus anticoagulant. The multivariate analysis found only three independent variables related to PVH and WMH: age, the diagnosis of SLE and cerebral atrophy.

Conclusions: Age, presence of SLE and presence of neurological symptoms were independently related with WMH and PVH, but not antiphospholipid antibodies.
Induction of in vitro heart block is not restricted to affinity purified anti-52 kDa Ro/SSA antibody from mothers of children with neonatal lupus
Authors: Viana V ST , Garcia S , Nascimento J HM , Elkon K B , Brot N , Campos de Carvalho A C , Bonfá E
Published: November 2003

The ability of affinity purified anti-52 kDa Ro/SSA antibody from patients without obstetric history of neonatal lupus to cause heart block using an experimental model was investigated. IgG-enriched fractions from sera of 20 systemic lupus erythematosus (SLE) and one Sjögren's syndrome (SS) all positives for anti-Ro/SSA antibodies as detected by CIE, were perfused on isolated whole rabbit hearts. Only six (29%) samples induced A-V block, five of them presenting low anti-Ro/SSA titre. All of them recognized the 52 kDa isoform on ELISA whereas only one had a concomitant binding to the 60 kDa protein. Moreover, affinity purified antibodies from two sera previously known to induce A-V block were obtained by affinity chromatography using a column containing the full-length 52 kDa Ro/SSA fusion protein. Paired eluate and effluent devoid of anti-52 kDa activity from the same patient were individually perfused in whole hearts. The ability to cause cardiac blockade was restricted to the affinity anti-52 kDa eluates. In addition, anti-52 kDa eluates from three IgG fractions that primarily failed to induce blockade remained ineffective. The present study has added to our knowledge that affinity anti-52 kDa Ro/SSA antibodies from mothers with healthy infants are capable of causing in vitro cardiac conduction disturbances. A prospective follow up of these patients will better delineate the clinical usefulness of this experimental model.
Naturally occurring anti-idiotypic antibodies reactive with anti-DNA antibodies in systemic lupus erythematosus
Authors: Williams W M , Isenberg D A
Published: November 2003

The levels of ‘putative’ anti-idiotypic antibodies reactive with F(ab0)2 fragments of affinity purified DNA binding antibodies from five SLE patients were measured in the serum of active and inactive systemic lupus erythematosus (SLE) patients, their relatives, spouses and healthy non-related individuals.

Serum anti-idiotypic antibodies of the IgG isotype could be detected in the serum of 8=15 inactive SLE patients, 3=19 active SLE patients, 17=27 SLE relatives, 1=4 SLE spouses and 6=32 healthy non-related individuals.

When the serum immunoglobulins from the individuals in each group were separated into IgG and IgM antibody fractions and analysed, a significant increase in levels of IgG anti-idiotypic reactivity were found in healthy individuals (16=32), whilst no significant increase in IgG anti-idiotypic antibodies were detected in SLE patients, SLE relatives and SLE spouses. Comparatively few individuals tested showed detectable levels of IgM anti-idiotypic antibodies.

These results demonstrate that anti-idiotypic antibodies reactive with anti-DNA antibodies are detectable in the serum of SLE patients, SLE relatives, SLE spouses and healthy individuals, and are predominantly of the IgG isotype. The increased frequency of IgG anti-idiotypic antibodies after separation from serum IgM antibodies infers that anti-idiotypic activity of some IgG immunoglobulins in the sera of healthy individuals may be masked by the presence of IgM antibodies in the serum.
Basaloid follicular hamartoma, total body hair loss and SLE
Authors: Morton S , Stevens A , Powell R J
Published: November 2003

We describe a patient with systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome (APLS) who developed a plaque-like lesion around the mouth and lost all body hair. Biopsies of the circumoral lesion and scalp, were originally reported as containing extensive basal cell carcinoma, but on review, both showed the typical appearance of a benign malformation of the hair follicle known as basaloid follicular hamartoma. Regrowth of hair and partial resolution of the peri-oral plaque occurred with more aggressive treatment of her SLE, but the basaloid follicular hamartomas in her scalp skin persisted. There is a known, but rare, association between this pattern of basaloid follicular hamartoma, alopecia and myasthenia gravis, but only two cases have been described in association with SLE and none with APLS.
DNAse treatment does not improve the survival of lupus prone (NZB6NZW)F1 mice
Authors: Verthelyi D , Dybdal N , Elias K A , Klinman D M
Published: November 2003

Objective: To examine the efficacy of deoxyribonuclease I (DNAse) therapy in the (NZB6 NZW)F1 murine model of lupus.

Methods: Lupus-prone female (NZB6NZW)F1 mice were treated daily with 0–15 mg/gof recombinant DNAse for 1–6 months. Parameters including anti-DNA autoantibody production, activation of cytokine secreting cells, kidney function and longevity were monitored.

Results: DNAse treatment selectively reduced the number of B cells secreting anti-dsDNA antibodies for approximately one month. However, neither short-term nor long-term treatment altered cytokine production, delayed the onset or reduced the severity of glomerulonephritis, or prolonged survival.

Conclusion: DNAse treatment initiated before, during, or after the onset of murine lupus did not improve clinical outcome.
Vasculitis in systemic lupus erythematosus
Authors: D'Cruz D
Published: November 2003

Vasculitis frequently complicates SLE, is associated with significant morbidity and mortality, and its pathophysiology is poorly understood. In seriously ill lupus patients with vasculitis, immunosuppression should almost always be considered.
Mixed cryoglobulinaemia: a cross-road between autoimmune and lymphoproliferative disorders
Authors: Ferri C , La Civita L , Longombardo G , Zignego A L , Pasero G
Published: November 2003

Mixed cryoglobulinaemia (MC) is a systemic vasculitis, secondary to the deposition in small and medium-sized blood vessels of circulating immune complexes, mainly the cryoglobulins, and complement. MC is characterised by a typical clinical triad (purpura, weakness, arthralgias) and by one or more organ involvement: chronic hepatitis, glomerulonephritis, peripheral neuropathy, skin ulcers and diffuse vasculitis. In a limited number of MC patients, a malignancy, that is B-cell non-Hodgkin's lymphoma or hepatocellular carcinoma, may also develop.

Hepatitis C virus (HCV) infection has been found in the majority of patients with MC; the frequency of HCV markers (91%) was significantly higher than other rheumatic diseases (6.4%), namely systemic lupus, Sjùgren's syndrome, rheumatoid arthritis and systemic sclerosis, or healthy controls (1.2%). The HCV infection of lymphoid tissues may represent the remote event leading to B-lymphocyte proliferation responsible for autoantibodies and immune-complex production. In a similar way, HCV infection may also be involved in the pathogenesis of other autoimmune (glomerulonephritis, thyroiditis, lung fibrosis, autoimmune hepatitis, porphyria cutanea tarda) and lymphoproliferative disorders (monoclonal gammopathies, B-cell lymphomas). MC shares numerous clinico-serological and pathological features with the above disorders. HCV seems to be their common etiological agent; however, a variable combination of unknown co-factors (infectious, genetic, environmental) should be determinant for the appearance of different clinical patterns.
Pathogenesis of vasculitis
Authors: Kallenberg C GM , Heeringa P
Published: November 2003

This review discusses current thoughts on the pathogenesis of vasculitis. Secondary vasculitides, frequently associated with infections or systemic autoimmune diseases, are, in most cases, characterized by immune deposits in the vessel wall, which probably underlies the development of lesions. In the primary vasculitides, immune deposits are generally absent. A group of primary vasculitides is, however, strongly associated with anti-neutrophil cytoplasmic autoantibodies (ANCA). Various in vitro and in vivo experimental data suggest that those ANCA are involved in the pathogenesis of lesions in the associated disorders.
Relationship between lupus nephritis activity and the serum level of soluble VCAM-1
Authors: Ikeda Y , Fujimoto T , Ameno M , Shiiki H , Dohi K
Published: November 2003

We measured the serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) in 72 patients with systemic lupus erythematosus (SLE) (including patients with active nephritis) and 33 normal control subjects, to investigate the correlation between levels of adhesion molecules and disease and histological activity. Serum samples were obtained at the time of renal biopsy in 27 patients with lupus nephritis. The 27 patients were divided into groups according to the World Health Organization (WHO) class as follows: class I / II, n = 11; class III / IV, n = 13 and class V, n = 3. We also determined the activity index (AI) in these 27 renal biopsy specimens. We obtained serial measurements of the serum levels of soluble adhesion molecules in 11 patients to examine the difference between active and remission stages. The serum level of sVCAM-1, but not sE-selectin or sICAM-1, was correlated with parameters of SLE disease activity, including the SLE disease activity index score, the anti-double stranded DNA antibody titer, the C3 level, the C4 level and the CH50 level. The serum levels of sVCAM-1, sE-selectin and sICAM-1 were significantly higher in patients with SLE than in controls (P = 0.006, P = 0.0005 and P = 0.04, respectively). The serum level of sVCAM-1 was significantly higher in patients with active lupus nephritis (WHO classes III and IV) than in patients in inactive lupus nephritis (WHO classes I and II) (P = 0.0016). The sVCAM-1 level was significantly elevated in patients with an AI > 4 compared with patients with an AI < 4(P = 0.0025). The sVCAM-1 level decreased significantly during remission (P = 0.0033).

The serum level of sVCAM-1 was elevated in patients with active lupus nephritis (WHO classes III and IV) and in patients with high AI scores. The serum level of sVCAM-1 was correlated with the SLE disease activity and decreased during remission. Therefore, the sVCAM-1 level may be a useful marker of lupus nephritis activity.
Using single-subject methodology to investigate psychiatric treatments in systemic lupus erythematosus
Authors: Iverson G L , Harnish M J , Paul R H
Published: November 2003

Psychiatric problems are frequently experienced by persons with systemic lupus erythematosus (SLE). Some researchers and clinicians presume that these psychiatric problems are a direct manifestation of the disease, while others suggest that psychosocial and environmental factors have greater etiological significance. Our lack of knowledge regarding the etiology of psychiatric problems in this population is a serious limitation to selecting treatment approaches or to understanding treatment efficacy. Studies that employ group research designs to investigate the etiology or treatment of psychiatric problems in patients with SLE are inherently limited. Therefore, this article provides a general introduction to single-subject methodology and illustrates some potential applications to investigating psychiatric treatments in persons with SLE.
Thrombogenic properties of antiphospholipid antibodies do not depend on their binding to β2 glycoprotein 1 (β2GP1) alone
Authors: Gharavi A E , Pierangeli S S , Gharavi E E , Hua T , Liu X W , Barker J H , Anderson G H , Harris E N
Published: November 2003

Immunization of mice with β2glycoprotein 1 (β2GP1) induces production of antiphospholipid (aPL) antibodies, which were shown to have thrombus enhancing properties in an experimental mouse model, indicating that these antibodies are thrombogenic in vivo. To determine whether the thrombogenic effect of murine antiphospholipid antibodies is due to their aPL or their anti-β2GP1 activity, we injected mice with murine monoclonal anticardiolipin (aCL) and anti-β2GP1 antibodies. Effects of these antibodies on thrombus formation, was evaluated utilizing a mouse model which enables kinetics of thrombus formation to be studied. The results of this study showed that the size of the thrombus in animals injected with murine aCL antibodies was larger than that in control groups. There was no difference in thrombus kinetics between anti-β2GP1 injected mice and controls, suggesting that the thrombogenic effect of aPL antibodies is not related to their anti-b2GP1 activity alone. Mice receiving monoclonal antibodies with both aCL and anti-β2GP1 activity, also increase thrombus size when compared with controls. These data indicate that murine aCL, but not anti-β2GP1, antibodies are thrombogenic in vivo.
Anti-β2-glycoprotein I and anti-prothrombin antibodies in patients with the ‘antiphospholipid’ syndrome: Immunological specificity and clotting profiles
Authors: Kandiah D A , Krilis S A
Published: November 2003

Lupus anticoagulant (LA) antibodies have been shown to be directed to protein-phospholipid complexes. In this study, we report on LA antibodies from patients with the ‘antiphospholipid’ syndrome (APS), that are directed to prothrombin and b2-glycoprotein I, but not to the complexes of these plasma proteins to anionic phospholipids. The anti-prothrombin antibodies studied had different reactivities in two clotting assays: the dilute Russell's viper venom time (dRVVT) and the dilute kaolin clotting time (dKCT). Anti-prothrombin and anti-b2-glycoprotein I (anti-b2GPI) antibodies, affinity-purified from one patient with APS were not cross-reactive and had different effects in the dRVVT and dKCT clotting tests. Polyclonal anti-prothrombin antibodies, affinity-purified on a prothrombin column, from two patients with prothrombin reactivity in their plasma, have affinity constants to prothrombin of 104 and 192 nM. The patient with affinity-purified antibodies to prothrombin and b2GPI, had affinity constants to prothrombin and b2GPI, respectively, of 192 nM and 3030 nM, respectively. LA antibodies are a heterogenous population of antibodies that have different immunological specificities and clotting test reactivities in different patients.
Fequency of antibodies to the cholesterol transport protein apolipoprotein A1 in patients with SLE
Authors: Dinu A R , Merrill J T , Shen C , Antonov I V , Myones B L , Lahita R G
Published: November 2003

In examining reasons for premature atherosclerosis in systemic lupus erythematosus (SLE), we previously reported low levels of the cholesterol transport protein apolipoprotein A1 (apoA1) in these patients, and specific antibodies to purified apoA1 were identified in the sera of 5 out of 30 lupus patients. The current study was initiated to determine whether these antibodies are common in lupus patients. 520 serum samples from 175 patients with SLE or primary antiphospholipid syndrome (PAPS) were tested for antibodies to purified apoA1. Positive sera were retested for binding to apolipoprotein incorporated into reconstructed nascent or mature high-density lipoprotein (HDL). Autoantibodies to apoA1 were found in 32.5% of patients with SLE and 22.9% of patients with PAPS, associated with the presence of aPL (anti-β2 glycoprotein-1, antiβ2 GP1) antibodies. When reconstructed, nascent and mature HDL molecules were compared as antigen-containing environments, positive sera reacted best to apoA1 embedded in mature HDL molecules. This report confirms the high prevalence of antibodies to apoA1 in patients with systemic lupus and suggests a high affinity of these antibodies for mature HDL.