Invasive aspergillosis in patients with systemic lupus erythematosus: a retrospective study on clinical characteristics and risk factors for mortality.

Objective The objective of this paper is to analyze the clinical features, outcomes, mortality risk factors, and all-cause mortalities of invasive aspergillosis (IA) in patients with systemic lupus erythematosus (SLE). Methods Medical records were reviewed to identify SLE patients with IA from January 2006 to June 2017, at Taipei Veterans General Hospital, Taiwan. A total of 6714 SLE patients were included. Clinical/laboratory parameters and treatment outcomes were analyzed. Results Four patients (19.0%) had definite and 17 had probable (81.0%) IA. Seven patients (33.3%) survived and 14 died (66.7%). Concurrently, there were 19 pneumonias (90.5%), 17 cases of other infections (81.0%), eight bacteremia (38.1%), nine cytomegalovirus (CMV, 42.7%) and six Candida (28.6%) infections. In all 55 blood cultures, 38 (69.1%) yielded gram-negative bacilli, of which carbapenem-resistant A. baumannii accounted for eight (21.1%); 17 (30.9%) yielded gram-positive cocci, of which methicillin-resistant S. aureus accounted for six (35.3%); and vancomycin-resistant Enterococcus accounted for four (23.5%). Daily steroid dose ≥ 20 mg (hazard ratio (HR) 2.00), recent pulse steroid therapy (HR 2.80), azathioprine (HR 2.00), rituximab (HR 2.00), plasmapheresis (HR 2.00), acute respiratory distress syndrome (HR 2.00), concurrent infections (HR 5.667) and CMV viremia (HR 1.75) were higher in the fatality group. All p values were less than 0.05. Septic shock ( n = 7, 50% in the fatality group) is the most common cause of mortality. Conclusions High daily steroid dosing, recent pulse steroid therapy, azathioprine, rituximab, concurrent infections, and CMV viremia were mortality risk factors for IA in SLE.

Increased serum fibroblast growth factor-23 and decreased bone turnover in patients with systemic lupus erythematosus under treatment with cyclosporine and steroid but not steroid only.

SUMMARY: In patients with systemic lupus erythematosus (SLE), low bone mineral density (BMD) is associated with increased age, prolonged disease, low body mass index (BMI), and overlap with rheumatoid arthritis (RA). Elevated fibroblast growth factor (FGF)-23 in cyclosporine A (CsA) users with SLE are associated with decreased active vitamin D and osteocalcin. INTRODUCTION: The objective of this study was to investigate the steroid and CsA effect on bone metabolism and serum FGF-23 in SLE patients. METHODS: Seventy-two SLE patients and 10 age- and sex-matched healthy individuals underwent blood tests for bone metabolic biomarkers and FGF-23, and lumbar spine dual-energy X-ray absorptiometry for BMD. RESULTS: Comparisons between patients and controls were made in premenopausal women/men younger than 50 years and postmenopausal women/men older than 50 years separately. SLE patients had more frequent low Z-score (≤-2.0, 8.5 vs. 0%), osteopenia (-2.5

High-density lipoprotein cholesterol and the risk of nephropathy in type 2 diabetic patients.

BACKGROUND AND AIMS: To date, few studies have demonstrated the impact of variations in blood pressure, blood glucose and lipid levels on the progression of diabetic nephropathy (DN) in type 2 diabetic patients. This study aimed to assess the associations of mean values and variability in metabolic parameters with the development of DN in type 2 diabetic patients. METHODS AND RESULTS: A total of 864 patients who had participated in a comprehensive diabetic care program for at least for 3 years were studied. Patients were stratified into progressor (n = 180) and non-progressor groups (n = 684) according to the status of progression of DN during the follow-up period. By Cox regression analysis, a higher mean HDL-C level was observed to be a protective factor against the progression of DN [hazard ratio (95% CI): 0.971(0.953-0.989), P = 0.002] and a higher HDL-C variation was found to be associated with a higher risk [hazard ratio (95% CI): 1.177(1.032-1.341), P = 0.015] of DN progression. By the Kaplan-Meier survival curve, patients with a higher HDL-C level and lower HDL-C variability were found to have the lowest risk of development of nephropathy. CONCLUSIONS: Our study demonstrated for the first time that type 2 diabetic patients under a standard disease management program who have a stable and a higher mean HDL-C level were associated with a lower risk of development of DN.

B lymphocyte-induced maturation protein 1 (BLIMP-1) attenuates autoimmune diabetes in NOD mice by suppressing Th1 and Th17 cells.

AIMS/HYPOTHESIS: Recent reports indicate that B lymphocyte-induced maturation protein 1 (BLIMP-1), encoded by the Prdm1 gene, expands its control over T cells and is associated with susceptibility to colitis in mice with T cell-specific BLIMP-1 deficiency. In this study, we aimed to investigate the potential role of BLIMP-1 in regulating autoimmune diabetes and T helper type 17 (Th17) cells. METHODS: We generated T cell-specific Blimp1 (also known as Prdm1) transgenic (Tg) or conditional knockout (CKO) NOD mice, in which Blimp1 is overexpressed or deleted in T cells, respectively. By side-by-side analysing these Tg or CKO mice, we further dissected the potential mechanisms of BLIMP-1-mediated modulation on autoimmune diabetes. RESULTS: Overproduction of BLIMP-1 in T cells significantly attenuated insulitis and the incidence of diabetes in NOD mice. Consistent with these results, the diabetogenic effect of splenocytes was remarkably impaired in Blimp1 Tg mice. Moreover, overproduction of BLIMP-1 repressed the proliferation and activation of lymphocytes and enhanced the function of regulatory T cells (Tregs) in NOD mice. In contrast, mice lacking BLIMP-1 in T cells markedly increased Th1 and Th17 cells, and developed highly proliferative and activated lymphocytes. Strikingly, overexpansion of Th1 and Th17 cells in CKO mice was significantly reduced by introducing a Blimp1 transgene, reinforcing the emerging role of BLIMP-1 in autoimmunity. CONCLUSIONS/INTERPRETATION: We conclude that BLIMP-1 orchestrates a T cell-specific modulation of autoimmunity by affecting lymphocyte proliferation and activation, Th1 and Th17 cell differentiation, and Treg function. Our results provide a theoretical basis for developing BLIMP-1-manipulated therapies for autoimmune diabetes.

Experimental osteoarthritis induced by surgical realignment of the patella in BALB/c mice.

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP. After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks. Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change.

Usefulness of human leucocyte antigen-B27 subtypes in predicting ankylosing spondylitis: Taiwan experience.

BACKGROUND: Genetic factors are clearly attributed to the susceptibility of ankylosing spondylitis (AS). The human leucocyte antigen (HLA)-B27 proved to be the very useful marker for diagnosing AS. The aim of this study was to determine the prevalence of HLA-B27 subtypes in Taiwan and to investigate whether these subtypes may be of help in predicting the diagnosis of AS. METHODS: A total of 314 patients with AS and a control group of 71 subjects positive for HLA-B27 detected by flow cytometry analysis were recruited for the study. HLA-B27 subtypes were confirmed by the polymerase chain reaction-sequence-specific primers and sequence-specific oligonucleotide probing. RESULTS: Four B27 alleles were identified: B*2704, B*2705, B*2706 and B*2707. HLA-B*2704 was the predominant allele. There were significant differences in the distribution of HLA-B27 subtypes between patients with AS and controls. Five of them who were homozygous for the B*2704 allele were solely found in AS group but not in controls. Statistical analysis showed that B*2704 was positively associated with AS, which suggested an increased possibility of having AS. Other HLA-B27 subtypes showed no strong correlation with AS. CONCLUSION: In the Taiwanese population, susceptibility to AS was determined by the presence of HLA-B*2704. Although B*2706 was reported to have a negative association with AS in Taiwanese, Thai and Chinese Singaporean populations, we report, in our study, two AS patients with B*2706 (0.6%). Disease heterogeneity suggests that other than genetic background, many pathogenic factors could be associated with AS. This may need to be investigated with a larger group of patients with AS and controls.

Interleukin (IL)-23 p19 expression induced by IL-1beta in human fibroblast-like synoviocytes with rheumatoid arthritis via active nuclear factor-kappaB and AP-1 dependent pathway.

OBJECTIVES: To explore the source of the p19 subunit of interleukin-23 (IL-23) in joints with rheumatoid arthritis (RA), the effects of IL-1beta and tumour necrosis factor (TNF)-alpha on IL-23 gene expression in RA fibroblast-like synoviocytes and the effect of IL-23 on proinflammatory cytokines. METHODS: Expression of IL-23 p19 in joints was examined by immunohistochemical analysis of patients with RA and osteoarthritis (OA). The effects of IL-1beta and TNF-alpha on the expression, of IL-23 p19 and IL-12 p35 subunits in human fibroblast-like synoviocytes from RA patients (HFLS-RA) were determined by reverse transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and western blotting assay. Blockade of nuclear factor kappaB (NF-kappaB) or AP-1 activation was used to verify the involvement of intracellular signal pathways of the induction of p19. IL-23-induced IL-8 and IL-6 productions were determined in HFLS-RA by RT-PCR and enzyme-linked immunosorbent assay. RESULTS: IL-23 p19 was expressed in the synovium from RA, but not from OA patients. Similar to the protein expression, IL-23 p19 mRNA could be detected by RT-PCR in four of five RA synovial fluid mononuclear cells (SFMC). IL-1beta and TNF-alpha could induce RA fibroblast-like synoviocytes to produce the IL-23 p19 subunit. The effects of IL-1beta were much stronger than TNF-alpha. These responses were observed in both a dose-responsive and time-dependent manner. IL-1beta produced weakly enhanced gene expression of the p35 subunits of IL-12. IL-1beta also promotes the p35 expression, a subunit of IL-12, but weakly. In addition, the NF-kappaB and the AP-1 inhibitors down-regulated the expression of IL-23 p19 mRNA induced by IL-1beta. IL-23 receptor (IL-23R) was of constitutive expression in HFLS-RA. Moreover, IL-23 up-regulated the IL-8 and IL-6 mRNA and protein levels in a dose-dependent manner in HFLS-RA. CONCLUSIONS: Our results demonstrate that IL-23, produced by mononuclear cells in synovial fluid with RA and HFLS-RA, promotes inflammatory responses in RA by inducing IL-8 and IL-6 production from HFLS. IL-1beta regulates IL-23 p19 expression via NF-kappaB and AP-1 pathways. This report also demonstrates that IL-23 could promote inflammatory responses in HFLS-RA by stimulating IL-8 and IL-6 production.

Adenovirus expressing interleukin-1 receptor antagonist alleviates allergic airway inflammation in a murine model of asthma.

Interleukin-1 (IL-1) is a proinflammatory cytokine and IL-1 receptor antagonist (IL-1ra) is a natural inhibitor that binds to IL-1 receptor type I without inducing signal transduction. It is suggested that IL-1 is required for allergen-specific T helper type 2 cell activation and the development of airway hyper-responsiveness (AHR), but the immunologic effect of exogenous IL-1ra in allergic asthma remains unclear. To examine the effect of IL-1ra on airway inflammation and immunoeffector cells in allergic asthma, recombinant adenovirus expressing human IL-1ra (Ad-hIL-1ra) was delivered intranasally into ovalbumin (OVA)-immunized mice. Single intranasal administration of Ad-hIL-1ra before airway antigen challenge in OVA-immunized mice significantly decreased the severity of AHR and reduced pulmonary infiltration of eosinophils and neutrophils. Suppression of IL-5 and eotaxin with concomitant enhancement of interferon gamma in bronchoalveolar lavage fluid was also noted in OVA-immunized mice by administration of Ad-hIL-1ra. In addition, histological studies showed that Ad-hIL-1ra was able to decrease OVA-induced peribronchial inflammation. Taken together, our results indicated that administration of Ad-hIL-1ra may have therapeutic potential for the immunomodulatory treatment of allergic asthma.

Sweet's syndrome as an initial presentation in systemic lupus erythematosus: a case report and review of the literature.

Malar or discoid rash is the most frequent specific cutaneous lesion for systemic lupus erythematosus (SLE). Neutrophilic dermatosis as an initial presentation in SLE is unusual. We describe a 38-year old female patient who primarily suffered from erythematous tender plaques and fever. Examination of skin biopsy of the plaques showed dense neutrophilic infiltration in the dermis. Polyarthritis, heavy proteinuria, photosensitivity and positive antinuclear antibodies (ANA > 1:1280) concluded the diagnosis of SLE. The plaques disappeared completely after treatment with systemic corticosteroids. To our knowledge, this is the first reported SLE patient with Sweet's syndrome as the initial presentation in literature review.

Dehydroepiandrosterone suppresses interleukin 10 synthesis in women with systemic lupus erythematosus.

OBJECTIVE: To study the effects of dehydroepiandrosterone (prasterone, DHEA) 200 mg/day on cytokine profiles in adult women with active systemic lupus erythematosus (SLE). METHODS: In a double blind, randomised, placebo controlled study conducted as part of a larger multicentre study, 30 adult women with active SLE received oral DHEA 200 mg/day or placebo for 24 weeks. Baseline prednisone (<10 mg/day) and other concomitant SLE medications were to remain constant. The levels of cytokines including interleukin (IL) 1, IL2, interferon gamma, IL4, and IL10 were determined by ELISA. The mean change from baseline to 24 weeks of therapy was analysed. RESULTS: The two groups (DHEA n = 15; placebo n = 15) were well balanced for baseline characteristics. Only IL1beta and IL10 could be detected in the serum of lupus patients; however, there was no significant mean (SD) difference in serum IL1beta before and after treatment (9.94 (8.92) v 9.20 (6.49) pg/ml). IL10 demonstrated a greater and significant reduction from baseline (9.21 (9.66) to 1.89 (1.47) pg/ml in the DHEA treatment group). CONCLUSIONS: In a 24 week study of adult Chinese women with mild to moderate SLE, treatment with DHEA 200 mg once daily resulted in significant reduction of serum levels of IL10. This finding may suggest why DHEA could significantly reduce lupus flares.

Ruptured renal microaneurysms complicated with a retroperitoneal abscess for a patient with systemic lupus erythematosus.

Renal artery aneurysm is extremely rare among patients with systemic lupus erythematosus.(SLE). Herein, we report on a 22-year-old male lupus patient who presented with acute abdominal pain, anemia and subsequent hypertension. Abdominal computed tomography revealed a peri-renal hematoma over the right kidney. A renal angiography revealed bilateral renal microaneurysms. The patient subsequently developed a right-side retroperitoneal abscess 4 weeks after hematoma formation and received an emergent laparotomy with drainage. Subsequent culture ofthe abscess-derived fluid revealed the presence of Proteus mirabilis and Escherichia coli. Following appropriate antipyretic and immunosuppressive drugs therapy, the patient recovered successfully. To the best of our knowledge, this is the first report of SLE associated with a retro-peritoneal abscess probably secondary to a ruptured renal microaneurysm.

The expression and significance of intracellular T helper cytokines in systemic lupus erythematosus.

To analyze the Th1 and Th2 paradigm of peripheral T helper cells in patients with systemic lupus erythematosus (SLE). The intracellular Th1 and Th2 cytokines were analyzed in fresh blood T cells from 20 SLE patients who had not yet received any treatment. Th1 and Th2 cells were quantitated based on their intracellular cytokine content as assessed by flow cytometry. Cytokine expressions were correlated with clinical features, laboratory findings, and disease activities. There was no difference in the expression of intracellular IFN-y, or IL-4 between SLE patients and healthy controls. However, the IL-2 and IL-10 levels were significantly higher and lower respectively in the lupus patients than in the control group. In addition, patients with arthritis had higher IFN-gamma expression than patients without arthritis. Moreover, patients with serositis or CNS involvement had higher IL-4 expression than in patients without these manifestations. There was no correlation between the SLEDAI scores and the cytokine expression levels. However, patients with serum anti-ds DNA antibodies had higher IL-10 levels than in those without these antibodies. The present study demonstrates that a Th1 pattern of intracellular cytokines predominates in patients with SLE prior to treatment. The pattern of particular intracellular T cell cytokines may suggest specific clinical manifestations and disease progression of SLE.

Endoscopic comparison of the gastroduodenal safety and the effects on arachidonic acid products between meloxicam and piroxicam in the treatment of osteoarthritis.

Our objective was to evaluate the efficacy, the gastroduodenal safety, and the effects on arachidonic acid products of meloxicam, a new acidic enolic non-steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2 over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in this double-blind parallel-groups randomised study. The efficacy for pain relief of the two tested medications was assessed by means of visual analogue scale and other clinical parameters. Pre- and post-treatment endoscopies were performed, and the findings were scored and recorded. The gastric fluid was aspirated at each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined by ELISA. There was no significant difference between the groups regarding the primary efficacy. Changes in endoscopic findings by means of Lanza score showed statistically significant differences between the two treatment groups in favour of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons showed a statistically significant difference (worsening) in gastric and total score with piroxicam, but no significant difference with meloxicam. The frequency of clinically relevant cases (total score >2) also showed a statistically significant worsening in the piroxicam group. The better GI tolerability of meloxicam was also suggested by fewer adverse GI events and no withdrawals due to adverse events compared with piroxicam. The pre-/post-study gastric juice concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/- 85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98 pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2 and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/- 50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4 weeks' treatment; however, there was no difference between these two groups. Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4 concentration significantly, and the between-groups difference was significant. Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with osteoarthritis of the knee.

Western and Chinese antirheumatic drug-induced T cell apoptotic DNA damage uses different caspase cascades and is independent of Fas/Fas ligand interaction.

Spontaneous or therapeutic induction of T cell apoptosis plays a critical role in establishing transplantation tolerance and maintaining remission of autoimmune diseases. We investigated the mechanisms of apoptosis induced by Chinese and Western antirheumatic drugs (ARDs) in human T cells. We found that hydroxychloroquine, Tripterygium wilfordii hook F, and tetrandrine (Tet), but not methotrexate, at therapeutic concentrations can cause T cell death. In addition, Tet selectively killed T cells, especially activated T cells. Although ARD-induced cytotoxicity was mediated through apoptotic mechanisms, Fas/Fas ligand interaction was not required. We further demonstrated that the processes of phosphatidylserine externalization and DNA damage along the ARD-induced T cell apoptotic pathway could operate independently, and that selective inhibition of DNA damage by caspase inhibitors did not prevent T cells from undergoing cell death. Moreover, we found that Tet- and Tripterygium wilfordii hook F-induced T cell DNA damage required caspase-3 activity, and hydroxychloroquine-induced T cell DNA damage was mediated through a caspase-3- and caspase-8-independent, but Z-Asp-Glu-Val-Asp-fluomethyl ketone-sensitive, signaling pathway. Finally, the observation that ARD-induced activation of caspase-3 in both Fas-sensitive and Fas-resistant Jurkat T cells indicates that Fas/Fas ligand interaction plays no role in ARD-induced T cell apoptosis. Our observations provide new information about the complex apoptotic mechanisms of ARDs, and have implications for combining Western and Chinese ARDs that have different immunomodulatory mechanisms in the therapy of autoimmune diseases and transplantation rejection.

Protective effect of lipophilic antioxidants on phorbol-induced acute lung injury in rats.

OBJECTIVE: To determine whether the lipophilic antioxidant U-74389G can ameliorate the acute lung injury induced by phorbol myristate acetate (PMA) in our isolated lung model in rats, and to compare its activity with the intracellular enzymes superoxide dismutase (SOD) or catalase. DESIGN: Randomized, controlled study. SETTING: Animal-care facility procedure room. SUBJECTS: Forty-two adult male Sprague-Dawley rats each weighing 250-350 g. INTERVENTIONS: Typical acute lung injury was induced successfully by PMA during 60 mins of observation. PMA (2 microg/kg) elicited a significant increase in microvascular permeability (measured by using the capillary filtration coefficient Kfc), lung weight gain, the lung weight/body weight ratio, pulmonary arterial pressure, and the protein concentration of the bronchoalveolar lavage fluid. MEASUREMENTS AND MAIN RESULTS: Pretreatment with 1 mg of U-74389G significantly attenuated the acute lung injury induced by PMA, all parameters having decreased significantly (p <.001). The protective effect of U-74389G was dose dependent, but SOD (6,000 U/kg) or catalase (50,000 U/kg) exhibited no protective effect. CONCLUSIONS: U-74389G significantly ameliorates acute lung injury induced by PMA in rats.

Infection of human dendritic cells by dengue virus causes cell maturation and cytokine production.

Dengue virus (DV) infection is a major problem in public health. It can cause fatal diseases such as Dengue hemorrhagic fever and Dengue shock syndrome. Dendritic cells (DC) are professional APCs required for establishing a primary immune response. Here, we investigated the role of human PBMC-derived DC in DV infection. Using different techniques, including plaque assay, flow cytometry analysis, nested RT-PCR, and confocal microscope and electron microscope examinations, we show that DV can enter cultured human DC and produce virus particles. After entrance, DV could be visualized in cystic vesicles, vacuoles, and the endoplasmic reticulum. The DV-infected DC also showed proliferation and hypertrophy of the endoplasmic reticulum as well as the swollen mitochondria. In addition, the DV-stimulated DC could express maturation markers such as B7-1, B7-2, HLA-DR, CD11b, and CD83. Furthermore, the infection of DC by DV induced production of TNF-alpha and IFN-alpha, but not IL-6 and IL-12. Although DC underwent spontaneous apoptosis in the absence of feeding cytokines, this process appeared to be delayed after DV infection. Our observations provide important information in understanding the pathogenesis of DV infection.

Aspirin differentially regulates endotoxin-induced IL-12 and TNF-alpha production in human dendritic cells.

OBJECTIVE: In the development of autoimmune diseases, dendritic cells (DC) play critical roles. Here, we examined the effect of aspirin on lipopolysaccharide (LPS)-induced DC activation. METHODS: The monocyte-derived DC were established. The cytokine production was measured by ELISA, reverse transcriptase/polymerase chain reaction, or intracellular staining analyzed by flow cytometry. The expression of cell surface molecules was determined by flow cytometry. RESULTS: Aspirin inhibited LPS-induced DC maturation and costimulatory molecules expression. Aspirin, at therapeutic concentrations, also decreased LPS-induced IL-12 and IL-10 production. In contrast, the LPS-induced TNF-alpha production was enhanced by aspirin. The differential effects of aspirin on IL-12 and TNF-alpha production may not be due to down-regulation of cyclooxygenase activities. CONCLUSION: The various effects of aspirin on LPS-stimulated DC may influence the understanding of the diverse immunomodulatory mechanisms of this anti-inflammatory drug.

Excellent effect of steroid plus azathioprine in a young woman with pernicious anaemia and systemic lupus erythematosus.

We describe a 29-year-old woman who developed pernicious anaemia 2 years after the diagnosis of systemic lupus erythematosus. This is a rare association despite the relationship between the autoimmune aetiologies of these two conditions. Seven other cases have been described, but our report demonstrates a case with an excellent response to steroid and azathioprine.