bluuebunny/crossref_metadata_2025 huggingface dataset:
Rate, pattern and factors related to damage in Brazilian systemic lupus erythematosus patients
Authors: Soares Márcio , Reis L , Papi J AS , Cardoso C RL
Published: November 2003

The Systemic Lupus InternationalCollaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI) is an accepted instrument to ascertain damage. It has been shown to vary among differentSLE populations.The aim of this study was to assess SDI score, pattern and factors related to damage in Brazilian SLE outpatients. The SDI was obtained in 105 patients with a median age of 41 (5-95%, 19-61.7) years and a median SLE duration of 127 (17.6-345.9) months. Patients had a median SDI of 2 (0-8) and 81.9% had some damage (SDI > 0). Damage was associatedwith a higher number of ACR criteria for SLE in multivariate analysis (OR 2.32, 95%CI 1.23-4.37, P 0.009). Antiphospholipid syndrome (APS) (OR 9.82, 95%CI 2.74-35.23, P < 0.001), methylprednisolone pulses (OR 3.91, 95%CI 1.19-12.81, P 0.024), age (OR 1.70, 95%CI 1.02-1.13, P 0.011) and prednisone use duration (OR 1.01, 95%CI 1.002-1.02, P 0.020) were related to severe damage (SDI ≥4). Hypertensionwas associated with renal, cardiac and atherosclerotic damage, as cyclophosphamide pulses were with premature menopause. In conclusion, damage was very frequent in Brazilian SLE patients, mainly due to skin involvement, compared to other SLE populations. The presence of APS was the major independent contributor to the development of severe damage. Arterial hypertension was identified as a common risk factor for renal, cardiac and atherosclerotic damage.
Remission of refractory lupus nephritis with a protocol including rituximab
Authors: Fra G P , Avanzi G C , Bartoli E
Published: November 2003

Immunosuppression with corticosteroids and cyclophosphamide is the standard of care for lupus nephritis. We report a 19-year old woman with lupus nephritis and nephrotic syndrome who had not achieved complete remission after treatment with 15.7g cyclophosphamideand 13.7g prednisone.We planned a consolidation phase with: 1) cyclophosphamide 20mg/kg i.v. every 28 days for three cycles; 2) anti-CD20 chimeric monoclonal antibody (rituximab) 375mg/m2 i.v. weekly for four weeks; and 3) slow tapering of prednisone p.o., q.o.d., after a reinduction dose during rituximab administration. At the end of this phase the patient achieved complete remission. An indefinite maintenance treatment with methotrexate, cyclosporin and low-dose prednisone was then started. Twenty-four months later the patient remains in remission. In the immunosuppressive treatment of lupusnephritisthe insertionof a consolidationphasewith rituximab combinedwith cyclophosphamide achieves a therapeutically important and lasting deletion of the lymphocyte clone responsible for autoimmunity.
Anticardiolipin antibodies in various diseases in Taiwan: a retrospective analysis
Authors: Tsai M-H , Tsai W-P , Liao S-T , Liou L-b
Published: November 2003

The goals of this study are to determine the frequency of anticardiolipinantibodies (ACA) in patients with various diseases and to evaluate the clinical significance of ACA in Taiwan. We collected 690 patients from ACA laboratory records. They were divided into eight groups in order to compare ACA percentages. Positive rates of ACA in different disease groups were below 20%, except for 38.2% in autoimmune diseases with vascular thrombosis. Compared with old stroke, the ACA positivity in young stroke was not significantly different (P 0.482). The positive percentage of lupus anticoagulant (LA) (2.86%) was lower than that of ACA (15.66%) in young stroke (P 0.015). Among patients with pregnancy loss or prematurity, the ACA positivity in lupus patients (44.44%) was higher than without lupus (9.76%; P 0.01). The prevalence of ACA is higher in patients with vascular thrombosis complicated by autoimmune diseases than with thrombosis alone in Taiwan. Young and old stroke do not differ in ACA positivity. Moreover, ACA is more prevalent than LA for young stroke related coagulation.The ACA positivity for pregnancy loss or prematurity is very low in Taiwan. In summary, this is the first report on the frequency of ACA and other coagulation factors in various diseases in Taiwan.
Renal involvement in primary antiphospholipid syndrome and its response to immunosuppressive therapy
Authors: Korkmaz C , Kabukcuoglu S , Isiksoy S , Yalçin A U
Published: November 2003

Antiphospholipid syndrome (APS) is the association between antiphospholipid antibodies, venous and arterial thrombosis and pregnancy morbidity. Although the kidney may be affected in APS, the treatment of renal involvement is yet to be elucidated.This report describes the clinical and laboratory features of four patients with primary APS nephropathy, and the beneficial effect of immunosuppressive therapy accompanied by warfarin and angiotensin-convertingenzyme inhibitor. We also briefly discuss the possible mechanisms of the beneficial effects of immunosuppressiveson primary APS nephropathy.
Systemic lupus erythematous with recurrent Guillain -Barré-like syndrome treated with intravenous immunoglobulins
Authors: Lewis M , Gibson T
Published: November 2003

We report on an unusual case of a young African male with systemic lupus erythematosus who developed an acute, severe Guillain-Barré-like peripheral neuropathy associated with ascites. The illness appeared to respond dramatically to a short course of intravenous immunoglobulins. Eight months later he had recurrence of identical features.He required respiratorysupport.On this occasion there was no response to intravenousimmunoglobulins or other measures and he died of sepsis after a protracted period of paralysis.
Epidemiology of systemic lupus erythematosus in a northern Spanish population: gender and age influence on immunological features
Authors: López P , Mozo L , Gutiérrez C , Suárez A
Published: November 2003

The present work was planned to research epidemiological and immunological features of systemic lupus erythematosus (SLE) in a Caucasian population from the north of Spain (Asturias). There is only one specialized immunology laboratory in this region where samples from all patients with a plausible or a firm diagnosis of SLE are referred for immunological analysis. Since 1992 we have reviewed registered data from samples submitted to the immunology laboratory with a firm, definitive diagnosis of SLE, based on the fulfillment of the American College of Rheumatology (ACR) criteria. We have constructed a database, which included 367 SLE patients. The point prevalencewas 34.12/100 000 (95% CI: 30.63-37.61/100 000), whereas the incidence rate calculated during the last five years was 2.15/100 000/year (95% CI: 1.76-2.54/100 000/year). The female/male ratio varied according to the age at diagnosis, being maximum (50: 1) between 22 and 28 years. The median age at diagnostis was significantly lower in females than in males. Immunological features also yielded sex and age peculiarities. The percentage of patients with anti-SSa antibodies yielded significant differences between males (18.6%) and females (34.6%). Anti-RNP and anti-Sm antibodies were more frequently present in childhood-onset patients, the difference with the oldest-onset group being statistically significant. Other analyses did not show significant differences, although, as a whole, we observed a trend towards a higher presence of autoantibodies related to an early disease onset.
Testing for anti-nucleosome antibodies in daily practice: a monocentric evaluation in 1696 patients
Authors: Ghillani-Dalbin P , Amoura Z , Cacoub P , Charuel J-L , Diemert M-C , Piette J-C , Musset L
Published: November 2003

The objective was to report our experience of the detection of anti-nucleosome (anti-Nuc) antibodies (Ab) in a large series of consecutive patients, and to compare these results with those of anti-nuclear and anti-dsDNA Ab. In total, 1696 consecutive patients with suspected or confirmed autoimmune disease were tested over a two-year period. The biological investigation included detection of anti-nuclear, anti-dsDNA and anti-Nuc Ab. Among 1696 sera, 382 (23%) were negative for all Ab tested (anti-nuclear, anti-dsDNA and anti-Nuc) and 1314 (77%) were positive for at least one Ab. Anti-Nuc Ab were positive in 350/1314 patients. In this group, 249/350 (71%) also had positive anti-nuclear and anti-dsDNA, 97/350 (28%) had only positive anti-nuclear Ab without anti-dsDNA Ab and 4/350 (1%) had both anti-dsDNA and anti-Nuc Ab without anti-nuclear Ab. No patient had ‘isolated’ anti-Nuc Ab. Clinical data were available for 307/350 anti-Nuc positive patients. Systemic lupus erythematosus (SLE) was diagnosed in 240/307 (78%) patients, including 43 SLE patients with negative anti-dsDNA Ab. In conclusion, this study extends the relevance of anti-Nuc Ab to routine use for the diagnosis of connective tissue diseases, mainly anti-dsDNA Ab negative SLE.
Spreading of the immune response from 52 kDaRo and 60 kDaRo to calreticulin in experimental autoimmunity
Authors: Kinoshita G , Keech C L , Sontheimer R D , Purcell A , McCluskey J , Gordon T P
Published: November 2003

Calreticulin (CR) is widely recognized as a new human autoantigen but there are conflicting data concerning its relationship with the Ro(SS-A) ribonucleoprotein (RNP). Recent evidence suggests that CR binds to 52 kDaRo (Ro52) by a protein/protein interaction and binds to hY RNA and rubella virus RNA. Other studies have shown that initiation of immunity to either Ro52 or 60 kDaRo (Ro60) can lead to reciprocal spreading of autoimmunity to Ro60 or Ro52, respectively, and induce anti-La autoantibodies in some strains of mice. These findings support a physical association of these polypeptides in Ro/La complexes. To test the hypothesis that CR is physically associated with Ro52 and/or Ro60 we examined the sera of Ro52-, Ro60 and La-immunized mice for intermolecular spreading to CR. Immune sera from BALB/c and C3H/HeJ mice immunized with recombinant 6xHis-mouse Ro52, 6xHis-human Ro60 or 6xHis-human La were tested for reactivity by ELISA and immunoblotting with a full-length human CR protein expressed as a soluble maltose binding protein fusion protein (CR-MBP). Five of the six Ro52-immunized C3H/HeJ mice sera and all six Ro60-immunized C3H/HeJ mice sera reacted with the CR-MBP (but not a MBP control) on ELISA. In the BALB/c group, the responder rate was lower with one in six of the Ro52-immunized and one in five of the Ro60-immunized mice spreading to CR. In contrast, none of the BALB/corC3H/HeJ mice which was immunized with La showed evidence of a recruited anti-CR antibody response. Immunoblotting of the different recombinant proteins with immune sera from the C3H/HeJ mice confirmed the specificity of the initial and recruited antibody responses. The spreading of immunity from Ro52 and Ro60 to CR in Ro-immunized mice suggests that a subpopulation of CR or CR-like molecules must associate under certain circumstances with Ro52 and Ro60 polypeptides in vivo, possibly as Ro/CR complexes concentrated in surface membrane blebs of apoptotic cells. The lack of spreading to CR in Laimmunized mice suggests that CR may be associated with a subpopulation of Ro particles from which La has already dissociated.
Anti-phospholipid-antibodies in patients with relapsing polychondritis
Authors: Zeuner M , Straub R H , Schlosser U , Rauh G , Schmitz G , Schòlmerich J , Lang B
Published: November 2003

Relapsing polychondritis (RP) is an extremly rare multisystemic disease thought to be of autoimmune origin. In order to assess if RP is associated with anti-phospholipid antibodies (aPL), clinical data and sera of 21 patients with RP were collected in a multicentre study. Concentration of anti-cardiolipin antibodies (aCL) (IgG-, IgM-and IgA-isotypes), anti-phosphatidylserine-antibodies (aPS) (IgG-and IgM-isotypes) and anti-β-2-glycoprotein I-antibodies (aβ2 GPI) were measured by ELISA. In eight patients aCL were found to be elevated. One patient had elevated aPS. No patient had elevated aβ2 GPI. No patient had clinical signs and symptoms of a aPL syndrome. Interestingly, the two RP patients with the highest aPL had concomitant systemic lupus erythematosus (SLE). Therefore the presence of elevated aPL in RP is probably more closely related to an associated SLE than to RP itself. There is no convincing evidence that aPL are associated with RP.
Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients
Authors: Shah N M , Khamashta M A , Atsumi T , Hughes G RV
Published: November 2003

We report a 10-year follow-up on 52 patients with raised levels of anticardiolipin antibodies (aCL) who were first seen at our tertiary referral centre in 1986. The clinical and serological features of these 52 patients are described. Thirty-one patients had the antiphospholipid syndrome (APS) in 1986. Nine of these patients (29%) had further thrombotic events during the follow-up period. Of the other 21 aCL positive patients without clinical manifestations of APS, 11 (52%) developed the syndrome over this period. Five patients (10%) died during the follow-up. Close monitoring of patients with connective tissue diseases and aCL is essential as the likelihood of developing antiphospholipid syndrome is high.
Refractory hiccough heralding transverse myelitis in the primary antiphospholipid syndrome
Authors: Ruiz-Argüelles G J , Guzmán-Ramos J , Flores-Flores J , Garay-Martínez J
Published: November 2003

The case of a 32-year-old female patient with a primary form of the antiphospholipid syndrome is presented. The initial symptom was a pathological form of hiccough, refractory to conventional therapy that was followed, weeks later, by a full-blown picture of transverse myelitis. Despite the fact that transverse myelitis has been described as associated with the presence of antiphospholipid antibodies, we could not find the description of refractory hiccough as the initial manifestation of the antiphospholipid syndrome. The administration of steroids, heparin and plasmapheresis resulted in resolution of the neurological symptoms.
Effect of extremely low dose cyclosporine treatment on the thrombocytopenia in systemic lupus erythematosus
Authors: Sugiyama M , Ogasawara H , Kaneko H , Hishikawa T , Sekigawa I , Iida N , Hashimoto H , Hirose S
Published: November 2003

Cyclosporine is widely known to be effective in cases involving both transplantation as well as a spectrum of immune-mediated diseases, although careful monitoring is required for the preemptive detection of its adverse effects. Here we report the successful treatment by extremely low dose cyclosporine (1 mg/kg per day) of two patients with thrombocytopenia in systemic lupus erythematosus.
Meta-analysis of the risk of venous thrombosis in individuals with antiphospholipid antibodies without underlying autoimmune disease or previous thrombosis
Authors: Wahl D G , Guillemin F , de Maistre E , Perret-Guillaume C , Lecompte T , Thibaut G
Published: November 2003

Patients with systemic lupus erythematosus (SLE) and antiphospholipid antibodies (aPL) are at a greater risk for venous thromboembolism (VTE) than SLE patients without these antibodies. For patients without SLE there is a controversy about the risk associated with these antibodies and about their prognostic significance. We reviewed the degree of evidence and describe the odds ratio for VTE associated with aPL, namely the lupus anticoagulant (LA) and anticardiolipin antibodies (aCL), in patients without SLE. The study was a meta-analysis of seven observational studies of risk for antiphospholipid associated venous thromboembolism (VTE), excluding SLE patients. The strategies to identify published research included a computerized literature search and the review of citations in primarily relevant articles for the period 1983 to 1997. A summary of study characteristics and a critical appraisal of study quality were done. Summary odds ratios were obtained conducted using a random and a fixed effects-model. The overall odds ratio for aCL associated VTE obtained by fixed-effects model was 1.56 (95% CI, 1.10—2.24) and 1.64 (95% CI, 0.93—2.89) by random-effects model. The heterogeneity of these results appeared to be due in part to the detection limit of the aCL assay: the odds ratio was 3.21 (95% CI, 1.11—9.28) with both models when high titres only were considered. The overall odds ratio for LA associated VTE was 11.1 (95% CI, 3.81—32.3). In conclusion meta-analysis of the risk for antiphospholipid associated thrombosis demonstrated a higher risk in patients with the LA than in other patients. This risk was also higher than in patients with aCL even when high titres only were considered.
Book Review: Systemic lupus erythematosus and thrombotic thrombocytopenic purpura. Report of three cases and review of the literature
Authors: Caramaschi P , Riccetti M M , Pasini A Fratta , Savarin T , Biasi D , Todeschini G
Published: November 2003

We describe three female patients affected by both systemic lupus erythematosus and thrombotic thrombocytopenic purpura, one with a fatal outcome. The literature about this disease association is reviewed.
Impact of disease activity and cumulative damage on the health of lupus patients
Authors: Fortin P R , Abrahamowicz M , Neville C , du Berger R , Fraenkel L , Clarke A E , Danoff D
Published: November 2003

To test if lupus activity and damage predict physical function and general health in lupus was the objective of this study. Ninety-six patients with lupus were seen at baseline and monthly for 4 months. Sociodemographic characteristics and lupus damage (SLICC/ACR DI), were collected at baseline while lupus activity (SLAM-R, SLEDAI), health status measures (HAQ, SF-36TM) and immunological tests were collected at each visit. Associations of lupus activity and damage with general health and physical function were evaluated. Baseline health status measures were greatly impaired and comparable to those of severe medical illnesses. In cross-sectional analyses, baseline activity score measured by SLAM-R, but not by SLEDAI, correlated with most subscales of SF-36TM. Baseline damage score SLICC ACR DI correlated only with the HAQ and the physical function subscale of SF-36TM. Differences in both activity measures (SLAM-R and SLEDAI) over time correlated with change in health status measures while baseline cumulative damage (SLICC/ACR DI) correlated with the average level of physical function only. Lupus activity measures, SLAM-R and SLEDAI, although differing cross-sectionally, both reflected patients' health status performance over time and lupus damage measure, SLICC/ACR DI, performed well in assessing physical function. Lupus patients scores for health are poor and comparable to those found in severe medical illnesses.
4-Aminoquinoline antimalarials enhance UV-B induced c–jun transcriptional activation
Authors: Nguyen T Q , Capra J D , Sontheimer R D
Published: November 2003

Previous work has documented that the earliest observable response in mammalian cells following ultraviolet (UV) irradiation is the activation of plasma membrane-associated Src tyrosine kinases. These molecules then trigger a signalling cascade that results in activation of the transcription factor AP-1 which subsequently transactivates the early immediate genes including c–jun. This pathway has been postulated to play a protective role against UV damage. As aminoquinoline antimalarials such as chloroquine are known to downregulate several photoinduced cutaneous disorders including LE-specific skin disease, we asked whether chloroquine might be capable of modulating this early limb of the UV light response. A431 cells (a human epidermal keratinocyte cell line) that had been transfected with a c–jun luciferase reporter gene construct were then treated with physiologically relevant concentrations of chloroquine followed by exposure to 0—125 J/m2 of UV-B from a bank of unfiltered FS20 lamps. Chloroquine pretreatment resulted in a dose–dependent increase in luciferase activity in permanently transfected A431 cells (luciferase activity was increased by 45% at 2.5 × 10-5 M chloroquine and 125 J/m2 of UV-B).

Hydroxychloroquine pretreatment also resulted in an increase in luciferase activity. Primaquine, an 8-aminoquinoline, did not influence the UV-B induced c- jun activity. Furthermore, chloroquine did not have a similar impact on HSP-70 gene activity during heat shock. These studies suggest that the beneficial effect of the 4-aminoquinoline antimalarials in various photodermatoses including cutaneous LE might result in part from the capacity of these drugs to enhance the protective early limb of the UV response.
Survival analysis of 306 European Spanish patients with systemic lupus erythematosus
Authors: Blanco F J , Gómez-Reino J J , de la Mata J , Corrales A , Rodríguez-Valverde V , Rosas J C , de la Camara A Gómez , Pascual E
Published: November 2003

Objective: To describe survival of lupus in South European Spanish patients.

Patients and Methods: Observational study of all SLE Spanish patients seen at three University Hospitals between 1975 and 1993. The charts of all patients were retrospectively reviewed. Sixtyfour clinic and laboratory variables were extracted from charts. Univariate analysis, multivariate Cox proportional hazard regression analysis, actuarial life tables and multiple logistic regression analysis were used to calculate survival probability and identify variables associated with survival.

Results: Three hundred and six (275 female and 31 male) patients were identified. Their mean age at diagnosis was 31.9 years (range 4 to 85). The mean duration of followup was 79 (1—126) months. Thirty-one patients died. The most common cause of death was infection (29%). Five, 10 and 15 years' survival rate was 90%–0.0158, 85%–0.0262 and 80%–0.0413, respectively. Log-rank analysis showed that male sex, proteinuria and nephropathy at diagnosis were associated with poor survival. By univariate and multivariate analysis male gender, nephropathy and CNS involvement were associated with worse survival.

Conclusion: In SLE patients from Spain, rate of survival is similar to other Caucasian patients, and better than other ethnic groups of Spanish ancestry. Other factors rather than genetic factors could explain our findings.
Renal expression of IL-6 and TNFα genes in lupus nephritis
Authors: Herrera-Esparza R , Barbosa-Cisneros O , Villalobos-Hurtado R , Avalos-Díaz E
Published: November 2003

These studies were carried out to examine the presence of the inflammatory cytokines IL-6 and TNFα in kidneys of patients with lupus nephritis as an indicator of their possible role in its pathogenesis. A total of 19 kidney biopsies from patients with type III or IV lupus nephritis were processed by direct immunofluorescence using monoclonal anti-IL-6 and TNFα antibodies. Local expression of these genes was demonstrated both by in situ hybridization and by reverse transcriptase-PCR amplification of total RNA isolated from kidney tissue. Fifty-two percent of the biopsies exhibited IL-6 and TNFα deposited along the glomeruli and tubules; in situ expression of these cytokines was demonstrated in 6 biopsies with type IV, and 1 with type III nephritis. Inflammatory cytokines are actively synthesized in the kidneys of patients with lupus nephritis and therefore, may play a role in its pathogenesis.
Familial coexistence of primary antiphospholipid syndrome and factor VLeiden
Authors: Schütt M , Klüter H , Hagedorn-Greiwe M , Fehm H L , Wiedemann G J
Published: November 2003

The antiphospholipid syndrome (APS) is an autoimmune thrombophilic disorder in which thromboembolism and thrombocytopenia occur. The antiphospholipid antibodies in these patients may cause acquired activated protein C resistance, whereas hereditary activated protein C resistance results from a common single point mutation in coagulation factor V (factor VLeiden). In a family of 11 members with 4 normal subjects, autoimmune thrombocytopenia was documented in 6 patients. Three out of these were found to have thrombocytopenia associated with primary APS. In addition, these 3 subjects were also heterozygous for the factor VLeiden. Only in this group of individuals did life threatening thromboembolic complications occur, while other thrombocytopenic family members showed no thrombotic manifestations. Genetic studies revealed no linkage between APS and HLA class II alleles. Taken together, we present a family with autoimmune thrombocytopenia, which is associated with primary APS in at least 50% of thrombocytopenic individuals. The coexistence of both APS and factor VLeiden in thrombocytopenic subjects, led to an increased number of thrombotic events, suggesting a critical role of combined acquired and hereditary activated protein C resistance in the development of thrombosis in this family. Since no association between APS and specific HLA groups was found, other underlying risk factors for the development of APS must be considered.
Clinical correlates, serum autoantibodies and the role of the major histocompatibility complex in French Canadian and non-French Canadian Caucasians with SLE
Authors: Podrebarac T A , Boisert D M , Goldstein R
Published: November 2003

Objective: To investigate the predisposing role of major histocompatibility complex (MHC) genes to autoantibody production and clinical manifestations comparing French Canadian and Non-French Canadian Caucasians with systemic lupus erythematosus (SLE)

Methods: Ninety-one Caucasian patients with SLE were studied. Clinical manifestations, autoantibody expression and HLA-A, B, (serology), DR, DQ and C4A gene deletion (restriction fragment length polymorphism [RFLP] typing) were determined.

Results: Photosensitivity was present in all SLE subjects with anti-Ro antibodies (P = 0.001, RR = 13.1, Cl = 1.8, 564). Photosensitivity was further associated with the HLA-A1, C4A gene deletion haplotype. More strikingly, C4A gene deletion was associated with anti-Ro (P = 0.008, RR = 4.6, Cl = 1.4, 16.2) and anti-La (P = 0.02, RR = 11.7, Cl = 1.4, 549) autoantibodies. This relationship was also significant for anti-Ro antibody in the French Canadian patients (P = 0.01, RR = 21.3, Cl = 1.7, 105.3). In contrast, anti-dsDNA autoantibodies were negatively associated with photosensitivity (P = 0.02, RR = 0.3, Cl = 0.07, 0.8) and correlated with HLA-DR15 (P = 0.006, RR = 4.2, Cl = 1.5, 12.8) and Dw2 (P = 0.009, RR = 3.9, Cl = 1.4, 11.9).

Conclusion: C4A gene deletion has a previously unrecognized powerful association with anti-Ro and anti-La autoantibodies. These results support the concept of divergent MHC gene associations with autoantibody expression and emphasize the influence of ethnicity on the immunogenetic study of SLE.
Dietary polyunsaturated fatty acids decrease anti-dsDNA and anti-cardiolipin antibodies production in idiotype induced mouse model of systemic lupus erythematosus
Authors: Reifen R , Blank M , Afek A , Kopilowiz Y , Sklan D , Gershwin M E , German B , Yoshida S , Shoenfeld Y
Published: November 2003

Objective: To examine the effect of diets with different polyunsaturated fatty acid contents, including linseed oil which contains 70% omega-3 fatty acids, on autoantibody production in idiotype induced mouse model of systemic lupus erythematosus (SLE).

Methods: Five different fats were fed to mice with induced SLE and antibody titers to anti-DNA and anti-cardiolipin were determined and histological examination of kidneys were carried out.

Results: SLE mice fed linseed oil showed lower titers of antibodies to DNA and to cardiolipin and less severe kidney damage than mice fed other diets, including fish oil.

Conclusion: Use of linseed oil may attenuate the severity of SLE and this diet may be recommended for other auto-immune diseases as well.
Serological markers in Arabs with lupus nephritis
Authors: Al Attia H M , Al Ahmed Y H , Chandani A U
Published: November 2003

The aim of this study was to characterize the autoantibody profile of Arabs with lupus nephritis (LN). Therefore, the records of 42 Arabs with classical systemic lupus erythematosus (SLE) were reviewed. Twenty one (50%) with LN and 21 without. Most patients with LN have developed their nephropathy within the first five years of the disease. Only C3 hypocomplementemia achieved statistically significant correlation in nephritic patients and anti ribonucleoprotein (RNP) antibodies in non-nephritic patients. The difference in anti double stranded DNA (dsDNA) antibodies was insignificant ( P = 0.107), as both groups had markedly high prevalence of these antibodies. In addition, there was no significant negative association between detectable rheumatoid factor (RI) and patients with LN. We also examined the spectrum of specific entities of antibodies that had previously been reported in association with LN in other series (anti Smith (Sm), RNP and SS-A without anti SS-B, anti SS-A and SS-B, anti RNP and Smith, anti RNP and dsDNA and anti RNP and SS-A antibodies). None has shown any correlation with renal disease, P = 1.00, P = 0.591, P = 0.613, P = 0.195 and P = 0.148, respectively. In conclusion, the study demonstrates that Arab patients with LN do not exhibit a distinctive serological profile, nonetheless it provides useful information to studies of SLE in different ethnic or racial groups.
Young Onset of Primary Sjögren's syndrome: clinical and immunological characteristics
Authors: Ramos-Casals M , Cervera R , Font J , Garcóa-Carrasco M , Espinosa G , Reino S , Pallarés L , Ingelmo M
Published: November 2003

The objective of our study was to determine the clinical and immunological characteristics of primary Sjögren's syndrome (SS) in patients with a young onset of the disease. We included 144 consecutive patients (134 female and 10 male; mean age at onset 53 y; range 20±87 y) 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 13 (9%) patients, disease onset occurred before the age of 35. All were female and the disease onset occurred between 20±34 y (mean, 28 y). When compared with patients with older onset, patients with a young onset of the primary SS presented a higher prevalence of lymphadenopathy (54% vs 6%, P < 0.001), rheumatoid factor (70% vs 39%, P = 0.034), anti-Ro/SS-A antibodies (70% vs 28%, P = 0.004) and monoclonal immunoglobulins (23% vs 4%, P = 0.02) in their sera. From the initial diagnosis of SS, three patients with a young-onset of the primary SS have developed lymphoproliferative disease at the time of the study, compared with one patient of the older-onset group (23% vs 1%, P = 0.002). Our study shows several differences between younger and older onset patients, including a higher incidence of lymphomas in the younger, thus confering to the age at onset of the disease a prognostic value.
Interleukin-2 and systemic lupus erythematosus—fifteen years later
Authors: Crispin J C , Alcocer-Varela J
Published: November 2003

Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder in which multiple immunologic abnormalities have been described. In this review, we thoroughly analyse the impaired T cell production of, and response to, interleukin-2 (IL-2) characteristic of patients with SLE. Since it was first reported, several articles have provided us with enlightening, but somewhat confusing, data that reveal the complexity of the subject. The IL-2 production by T cells is part of a complex network in which a discrete alteration is capable of disrupting the whole system. On the other hand, regulatory mechanisms exist that, in an attempt to compensate the primary alteration, provoke secondary defects. Evidence indicates that this defect is not intrinsic, but rather, results from multiple microenvironmental influences that act on the T cell and modify its activation state and its cytokine production. Abnormalities in co-stimulatory mechanisms and in cytokines that may be related to the IL-2 production deficiency, have been described in patients with SLE. We also consider the information derived from murine SLE models, IL-2 knockout models and reports concerning the immune dysregulation present in patients with SLE.
Systemic lupus erythematosus VII: frequency and impact of secondary Sjøgren's syndrome
Authors: Nossent J C , Swaak A JG
Published: November 2003

Background: The prognosis of patients with systemic lupus erythematosus (SLE) largely depends on the severity of cumulative organ damage during the course of the disease. While Sjùgren's syndrome (SS) predominantly affects exocrine glands, a considerable number of patients develop visceral organ damage. Thus, the occurrence of a secondary SS (2°SS) in SLE patients, may result in more extensive organ damage and thereby adversely affect prognosis.

Patients/Methods: 138 patients meeting the 1982 American College of Rheumatology (ACR) classification criteria for SLE were prospectively studied over a mean period of ninety months. 2°SS was diagnosed according to the 1993 European Study Group criteria and complication rates and prognosis were compared between patients with and without SS.

Results: 27 patients (19%) developed SS after a mean period of 48 months. There was a gradual increase in SS prevalence over time after SLE-onset. 2°SS patients were older (mean age 41 vs 35 years, P = 0.03), had less renal disease (19% vs 38%, P = 0.04), more thrombocytopenia (26% vs 9%, P = 0.05) and similar serological profiles (including anti-SSa) as patients without SS. Overall mortality was lower in patients with SS (4% vs 13.5%, P = 0.01), while lifetable analysis showed improved survival estimates for 2°SS patients with borderline statistical significance (P = 0.06).

Conclusions:2SS develops in about one-fifth of SLE patients in a time-dependent fashion: these patients are older, have less renal involvement and their prognosis is at least as good as for those remaining free of SS.
Polyarteritis nodosa, microscopic polyangiitis and Churg–Strauss syndrome
Authors: Lhote F , Cohen P , Guillevin L
Published: November 2003

Polyarteritis nodosa (PAN), first described by Küssmaul and Maier, is a well-known form of necrotizing angiitis whose manifestations are weight loss, fever, asthenia, peripheral neuropathy, renal involvement, musculoskeletal and cutaneous manifestations, hypertension, gastrointestinal tract involvement, and cardiac failure. Recently individualized from PAN, microscopic polyangiitis (MPA) is a systemic vasculitis of small-size vessels whose clinical manifestations are very similar to those of PAN, but it is characterized by the presence of rapidly progressive glomerulonephritis (RPGN), which is nearly constant, and pulmonary involvement usually absent in PAN. Churg–Strauss syndrome (CSS) is a disorder characterized by hypereosinophilia and systemic vasculitis similar to that of PAN and occurring in individuals with asthma and allergic rhinitis. Considering the etiologies of PAN, primary and secondary vasculitides can also be distinguished because PAN can be the consequence of hepatitis B virus (HBV) infection and sometimes of other etiologic agents.

The prognosis of systemic vasculitides has been transformed by corticosteroids that are, except in HBV-related PAN, the basic treatment. Immunosuppressive drugs, especially cyclophophamide, have also contributed to improving the prognosis, but their precise role in the management of these vasculitides is still being elucidated.
Childhood vasculitis
Authors: Dillon M J
Published: November 2003

Vasculitis can and does occur in childhood. Apart from the relatively common vasculitides (Henoch–Schönlein purpura, Kawasaki disease and in world wide terms Takayasu disease) there are a number of important but comparatively rare disorders affecting children. These include macroscopic and microscopic polyarteritis, cutaneous polyarteritis, Wegener's granulomatosis, Churg–Strauss syndrome, primary angiitis of the central nervous system, hypersensitivity angiitis, hypocomplimentaemic urticarial vasculitis, vasculitis associated with various connective tissue disorders and vasculitis associated with conditions such as Behçets syndrome, familial Mediterranean fever and Cogan's syndrome. Distinguishing these conditions from other disorders is often difficult and requires clinical acumen and appropriate investigative procedures. With modern therapeutic agents, it is possible to implement appropriate therapy but in spite of this, there remains a not inconsequential morbidity and mortality.
Giant cell arteritis
Authors: Hunder G G
Published: November 2003

In many populations giant cell arteritis (GCA) is the most common form of vasculitis. Genetic markers, ethnic factors, and increasing age over 50 years appear to enhance susceptibility and an infection may trigger its onset. Recent investigations provide evidence that the vasculitic reaction is part of an immune response to an antigen residing in involved artery walls. These studies along with the description of an experimental model of the disease have significantly increased out understanding of GCA.
Wegener's granulomatosis: disease course, assessment of activity and extent and treatment
Authors: de Groot K , Gross W L
Published: November 2003

Wegener's granulomatosis (WG) belongs to the group of necrotizing primary systemic vasculitides of unknown etiology, that are associated with anti-neutrophil cytoplasmic antibodies. The pathological hallmark of WG is the coexistence of vasculitis and granuloma. Due to more sensitive diagnostic instruments, especially ANCA testing, the incidence of diagnosis of WG has risen in the past ten years. Although the precise pathophysiology is not understood yet, there is ample evidence that ANCA, which can lead to cytotoxic reactions in the vascular texture, play a major role, possibly promoted by a dysbalance in the anti-idiotypic network. The clinical disease course is typically two-phasic, beginning with a granulomatous inflammation of the upper respiratory tract, that usually is followed by a generalized vasculitic phase, that can range from mild organ dysfuntion to lifethreatening multi-organ failure. Consequently, diagnostic procedures, patients' assessment and therapeutic regimens need to be individualized, adapted to stage and activity of the disease as well as standardized.
Self Ig peptides that help anti-DNA antibody production: importance of charged residues
Authors: Hahn B H , Singh R R , Ebling F M
Published: November 2003

Young NZB/NZW F1 (BWF1) mice develop T cell repertoires that are spontaneously stimulated by peptides derived from the VH regions of BWF1 J558-encoded autoantibodies (autoAb) to DNA, but not to VH region peptides of a J558-encoded antibody to an exogenous antigen. Immunization of young BWF1 mice with selected Ig-derived peptides accelerates anti-DNA production and nephritis, and immune tolerance induction to a combination of these determinants delays anti-DNA production and disease onset. To further characterize this immunoregulatory circuitry, we asked whether this phenomenon of spontaneous T cell activation by VH region peptides is restricted to anti-DNA Ab of the VH J558 family, and what are the charge and structural attributes of these T cell determinants? We studied spontaneous T cell proliferative responses to peptides derived from an autoAb to DNA constructed from VH 7183 and found that it contains several T cell determinants. Both charge and size of certain amino acids (AA) within each peptide seemed to be important. Peptides containing arginine (R) or glutamic acid (E) were more likely to be T cell determinants than peptides without those AA; replacement of charged AA with uncharged AA abolished T cell recognition of a peptide. We previously reported that some Abs to DNA are enriched in R in their VH; pathogenic BWF1 IgG anti-DNA are enriched in positively and negatively charged AA in VH Therefore, we speculate that peptides from natural IgM autoAb may initially activate BWF1 T cells, and as somatic mutations of Ig occur, charged AA introduced into V regions increase the number of T cell determinants, thus favoring upregulation of pathogenic Ab subsets. Therefore, in predisposed individuals, the ability of T cells to recognize more charged T cell determinants in autoAb may be one mechanism promoting development of disease.
Acute acalculous cholecystitis in systemic lupus erythematosus: a case report and review of the literature
Authors: Kamimura T , Mimori A , Takeda A , Masuyama J , Yoshio T , Okazaki H , Kano S , Minota S
Published: November 2003

A 27-year-old woman with systemic lupus erythematosus (SLE) was found to have acute acalculous cholecystitis. At the time of admission, the patient was not under corticosteroid or immunosuppressive therapy. Computed tomography (CT) and ultrasonography revealed findings in the gall bladder consistent with acute acalculous cholecystitis. Her abdominal pain completely disappeared following corticosteroid therapy, with dramatic improvement in the images of CT and ultrasonography. Six similar cases of SLE complicated with acute acalculous cholecystitis have been reported in the literature and they were all treated surgically by cholecystectomy or cholecystostomy. This is the first case report in which acute acalculous cholecystitis accompanying SLE was treated successfully by corticosteroid without surgical intervention.
Platelet activation and turnover in the primary antiphospholipid syndrome
Authors: Joseph J E , Donohoe S , Harrison P , Mackie I J , Machin S J
Published: November 2003

Thromboembolism is a common occurrence in patients with the antiphospholipid syndrome (APS). The mechanism responsible for this phenomenon is unclear; there are several theories. One possibility is that a pathogenic interaction exists between antiphospholipid antibodies and platelets, leading to their activation. This study examined the expression of the platelet activation markers CD62 and CD63 by flow cytometry in 20 patients with the primary antiphospholipid syndrome (PAPS). Levels of soluble P-selectin were also assayed. Reticulated platelets were measured as an indicator of increased platelet production and/or turnover. Median CD63 expression was significantly increased in patients (14.3%) compared to a group of healthy controls (10.1%, P , 0.0008). There was no significant difference in median CD62 expression or percent reticulated platelets between the two groups. The median level of soluble P-selectin was significantly higher in PAPS patients (35.5 ng/ml) compared to controls (18.8 ng/ml, P , 0.0028). Patients receiving aspirin had lower median CD63 values (13.1%) when compared to those patients who were not (18.0%, P , 0.023). However, aspirin therapy did not prevent significant platelet activation occurring in some individual patients.

Our data suggest that although not excessive, there is a degree of increased platelet activation in some PAPS patients, which is not always suppressed by antiplatelet therapy with aspirin.
Defective early T and T-dependent B cell activation in systemic lupus erythematosus
Authors: Fernández-Gutiérrez B , de Miguel S , Morado C , Hernández-García C , Bañares A , Jover J A
Published: November 2003

Systemic lupus erythematosus (SLE) is characterized by autoantibody production of unknown origin. Since T-B cell interaction is a key event to produce antibodies, we investigated this interaction through study of CD69, CD40 ligand (CD40L) and CD23 expression (three very early activation antigens). Peripheral blood mononuclear cells (PBMC) from inactive lupus patients were studied following culture with either medium alone, anti-CD3 monoclonal antibody (mAb), recombinant interleukin-4 (rIL-4) or phorbol myristate acetate (PMA)–ionomycin. Analysis of CD23 expression on lupus B cells in basal conditions and after anti-CD3 challenge of PBMC, a reflection of cognate interaction between T and B cells, was clearly defective. Conversely, CD23 expression on lupus B cells following non-cognate T cell signals (rIL-4) was preserved.

CD69 and CD40L expression was also impaired in lupus T cells following anti-CD3 challenge. Nonetheless, activation by means of PMA and/or ionomycin was preserved both in T cells (CD69 and CD40L expression) and in B cells (CD23 expression).

These results indicate that B cells from inactive lupus patients display a normal early response to direct B-cell stimuli. Conversely, T-dependent B-cell stimuli are clearly defective in SLE patients in remission. These results indicate that T-B cognate interaction related to defective T cell activation located between surface membrane and protein kinase C (PKC)=ionomycin function is an intrinsic characteristic of these patients.
Subacute cutaneous lupus erythematosus associated with cinnarizine and thiethylperazine therapy
Authors: Toll A , Campo-Pisa P , González-Castro J , Campo-Voegeli A , Azoón A , Iranzo P , Lecha M , Herrero C
Published: November 2003

We report the case of a woman who developed subacute cutaneous lupus erythematosus (SCLE) after exposure to the sun while taking cinnarizine and thiethylperazine. The patient recalled that 10 years previously, a similar eruption had appeared after sunbathing, while she was taking only cinnarizine. SCLE development in this patient was probably drug related and there is some evidence that cinnarizine played an important pathogenic role.
Anti-prolactin autoantibodies in systemic lupus erythematosus patients with associated hyperprolactinemia
Authors: Leaños A , Pascoe D , Fraga A , Blanco-Favela F
Published: November 2003

Hyperprolactinemia has been found in a subset of systemic lupus erythematosus (SLE) patients. In order to explore whether antibodies to prolactin (PRL) play a role in SLE patients with associated hyperprolactinemia, we performed a cross-sectional study in which 259 consecutive SLE patients were tested for hyperprolactinemia and anti-prolactin autoantibodies. Forty-one (15.8%) had prolactin levels above the norm. The frequency of anti-PRL autoantibodies in hyperprolactinemia was 2=14 (14.3%). In the SLE patients with ‘idiopathic hyperprolactinemia’, 11=27 (40.7%) had anti-PRL antibodies. The levels of serum PRL were significantly higher in patients with idiopathic hyperprolactinemia and anti-PRL autoantibody compared to the patients with idiopathic hyperprolactinemia who were anti-PRL autoantibody-negative. Patients with idiopathic hyperprolactinemia and anti-PRL autoantibody had relatively low SLE disease activity index (SLEDAI) scores and significantly different laboratory parameters compared to those with idiopathic hyperprolactinemia and no anti-PRL antibody. There was a significant correlation between titers of the anti-PRL autoantibody and serum PRL levels (rs = 0.98, P = 0.0001). These data suggest that anti-PRL antibodies could be the cause of hyperprolactinemia in a subset of SLE patients, especially those with particularly high serum prolactin levels with a diagnosis of ‘idiopathic hyperprolactinemia’. The patients with anti-PRL antibody had fewer clinical manifestations and less serological activity, indicating that biological activity of PRL was attenuated by the autoantibody.