Disorders In Systemic Lupus Erythematosus Research Articles

Vitamin D: Extra-skeletal effects

There is a growing concern of vitamin D deficiency and its relationship with several extra-skeletal pathological states, ranging from immune disorders (systemic lupus erythematosus, type 1 diabetes mellitus, multiple sclerosis, inflammatory bowel diseases, and rheumatoid arthritis), cardiovascular disorders (coronary artery disease, atherosclerosis, and hypertension), infections (viral and bacterial), endocrine disorders (growth failure, infertility in males, metabolic syndrome, and type 2 diabetes mellitus), neuro-psychiatric, and neuro-degenerative disorders, renal disorders, chronic lung disorders to cancer. Besides its positive effects on the musculo-skeletal system, vitamin D has shown to take an active part in the regulation of cellular proliferation, differentiation, apoptosis, and angiogenesis. It has been shown to control approximately 3% of the human genes directly or indirectly. Although there is a strong body of evidence toward implication of vitamin& D deficiency with several extra-skeletal disorders, it remains unclear if vitamin D supplementation may slow down, halt or even reverse the disease processes. This review aims to discuss the potential associations of vitamin D with various extra-skeletal disorders.

抗アクアポリン4抗体のほか複数の自己抗体をともなった視神経脊髄炎の1例

We report a patient with optic neuropathy and longitudinally extensive myelitis associated with anti-aquaporin 4 (AQP4) antibody and other autoantibodies. An 89-year-old woman presented with progressive numbness and weakness of the extremities which had acutely developed. She also complained of neck pain and gait disturbance. The results of a general physical examination were unremarkable. Neurologic examination disclosed right optic atrophy, an absence of touch sensation, pain, and muscular weakness in all her extremities. Her deep tendon reflexes were decreased, and the Babinski sign was bilaterally positive. Immunoserologic study yielded positive titers for anti-nuclear antibody (ANA), anti-double-stranded DNA, anti-Sjögren syndrome (SS)-A, anti-SS-B, and anti-ribonucleoprotein (RNP) antibodies. A lumbar cerebrospinal fluid examination showed a protein concentration of 54 mg/dL, a glucose concentration of 50 mg/dL (simultaneous blood concentration, 140 mg/dL), and a cell count of 2/mm(3). Chest radiography revealed interstitial pneumonia. Magnetic resonance imaging (MRI) of the cervical spine showed spondylotic cervical canal stenosis with cord impingement. T2-weighted MR images demonstrated increased signal intensity extending from C2 to C6, while contrast enhancement was noted in T1-weighted MR images upon gadolinium-DTPA administration. We suspected longitudinally extensive myelitis associated with the autoimmune disorders systemic lupus erythematosus and Sjögren syndrome. After intravenous methylprednisolone administration, her neurologic abnormalities gradually decreased, while MRI no longer showed increased signal or contrast enhancement. Anti-AQP4 antibody titers were positive. We consider that this patient had a neuromyelitis optica (NMO) spectrum disorder which was associated with systemic autoimmune disease. The possibility of NMO should be considered in similar patients with autoimmune disease, and anti-AQP4 antibody should be assessed.

Increased cardiac injury in NZB/W F1 mice received antibody against human parvovirus B19 VP1 unique region protein

Human parvovirus B19 (B19) infection has been postulated to both myocardial injury and development of systemic lupus erythematosus (SLE). However, the influence of anti-B19-VP1u antibodies on cardiac disorders in SLE is still obscure. To elucidate the effects of anti-B19-VP1u IgG in SLE, passive transfer of PBS, normal rabbit IgG or rabbit anti-B19-VP1u IgG was injected intravenously into NZB/W F1 mice, respectively. Significant expression of IL-1β, IL-6 and TNF-α were detected in NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Markedly cardiomyocyte disarray and lymphocyte infiltration were observed in left ventricle of hearts from NZB/W F1 mice receiving rabbit anti-B19-VP1u IgG. Additionally, significant increases of matrix metalloproteinase-9 (MMP9) activity and protein expression were detected in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. Accordingly, significant increase of phosphorylated p-38 and NF-κB proteins were observed in left ventricle of hearts from NZB/W F1 mice receiving B19-VP1u IgG. However, no significant variation of cardiac atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), heart-type fatty acid-binding protein (h-FABP) and creatine kinase MB (CK-MB) were detected among all experimental groups. These findings firstly demonstrated the aggravated effects of anti-B19 VP1u IgG on cardiac injury by induction of inflammatory but not myocardial infarction-associated proteins through activation of phosphorylated p-38 and NF-κB signaling.

Identification of Three New Autoantibodies Associated with Systemic Lupus Erythematosus Using Two Proteomic Approaches

Our objective was to identify new serum autoantibodies associated with systemic lupus erythematosus (SLE), focusing on those found in patients with central nervous system (CNS) syndromes. Autoantigens in human brain proteins were screened by multiple proteomic analyses: two-dimensional polyacrylamide gel electrophoresis/Western blots followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and immunoprecipitation followed by liquid chromatography-tandem mass spectrometry shotgun analysis. The presence of serum IgG autoantibodies against 11 selected recombinant antigens was assessed by Western blot and enzyme-linked immunosorbent assay (ELISA) in the sera of 106 SLE patients and 100 normal healthy controls. The O.D. values in sera from SLE patients were significantly higher than those of controls for the antigens crystallin αB (p = 0.0002), esterase D (p = 0.0002), APEX nuclease 1 (p < 0.0001), ribosomal protein P0 (p < 0.0001), and PA28γ (p = 0.0005); the first three are newly reported. The anti-esterase D antibody levels were significantly higher in the CNS group than in the non-CNS group (p = 0.016). Moreover, when the SLE patients were categorized using CNS manifestations indicating neurologic or psychiatric disorders, the anti-APEX nuclease 1 antibody levels were significantly elevated in SLE patients with psychiatric disorders (p = 0.037). In conclusion, the association of SLE with several new and previously reported autoantibodies has been demonstrated. Statistically significant associations between anti-esterase D antibodies and CNS syndromes as well as between anti-APEX nuclease 1 antibodies and psychiatric disorders in SLE were also demonstrated. The combined immunoproteomic approaches used in this study are reliable and effective methods for identifying SLE autoantigens.

Common mental disorders and psychological distress in systemic lupus erythematosus are not associated with disease activity

Psychiatric diagnosis in patients with systemic lupus erythematosus (SLE) is controversial: variations have been reported in frequency, diagnostic assays, associations with disease activity, autoantibodies, and contributing social factors. Eighty-three consecutive non-selected Chilean patients with SLE were evaluated for: (i) 26 common mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), using the Mini-International Neuropsychiatric Interview (MINI-plus); (ii) psychological suffering measured by Hospital Anxiety and Depression Scale (HADS); (iii) ACR 1999 neuropsychiatric (NP)SLE criteria; (iv) SLE disease activity (SLEDAI-2K); (v) cumulative damage (SLICC/ACR); and (vi) anti-ribosomal P antibodies by enzyme-linked immunoassay and immunoblot. Psychiatric diagnoses occurred in 44.6% of patients; the most frequent (21.7%) was major depressive episode (MDE). No association with lupus activity was observed in patients with a DSM-IV diagnosis or MDE or psychological suffering. ACR 1999 NPSLE criteria were present in 42.2% of patients, the majority corresponding to mood (28.9%) or anxiety disorders (15.6%). Suicidal risk was present in 9.6% of patients. Anti-ribosomal P antibodies (13.3%) were not associated with DSM-IV diagnosis. Severe psychiatric disorders in SLE are common and not associated with disease activity.

The spectrum of thyroid disorders in systemic lupus erythematosus

To study the spectrum of thyroid disorders in systemic lupus erythematosus (SLE). Hundred SLE patients as per American Rheumatology Association(ARA) classification criteria underwent clinical examination, including assessment of disease activity (SLEDAI) and laboratory evaluation for serum triiodothyronine (T3),free thyroxine (FT4), thyroid stimulating hormone (TSH), antithyroperoxidase (TPO) antibody and antithyroglobulin (TG) antibody. Hundred age- and sex-matched apparently healthy individuals served as control. Thirty-six (36%) lupus patients had thyroid dysfunction when compared to 8 (8%) of controls and all of them were women. Primary hypothyroidism was the commonest dysfunction in 14 (14%), while subclinical hypothyroidism and subclinical hyperthyroidism was seen in 12 (12%) and 2 (2%), respectively. Eight (8%) had isolated low T3 consistent with sick euthyroid syndrome. Eighteen (50%) of thyroid dysfunction were autoimmune in nature (autoantibody positive) and rest 18 (50%) were non-autoimmune. Euthyroid state with the elevation of antibodies alone was seen in 12 (12%) of the lupus patients. In contrast, only 5 (5%) of controls had primary hypothyroidism and 3 (3%) had subclinical hypothyroidism, while none had hyperthyroidism. SLEDAI score and disease duration were compared between lupus patients with thyroid dysfunction to those with normal thyroid function. A statistically significant association was found between SLEDAI and thyroid dysfunction of sick euthyroid type.SLE disease duration had no statistically significant association with thyroid dysfunction. Prevalence of thyroid autoantibodies in lupus patients was 30% when compared to 10% of controls. Ninety-six (96%) of the SLE patients were ANA positive, while 4 (4%) of them were ANA negative but were anti-Sm antibody positive. There were no suggestions of any other autoimmune endocrine diseases like diabetes or Addison's disease (clinically and on baseline investigations) in our lupus cohort and hence no further work up was done for these diseases. Thyroid disorders are frequent in SLE and are multifactorial with a definite higher prevalence of hypothyroidism as well as thyroid autoantibodies.

Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus

The origins and consequences of a regulatory T cell (Treg) disorder in systemic lupus erythematosus (SLE) are poorly understood. In the (NZBxNZW) F1 mouse model of lupus, we found that...

Homeostatic imbalance of regulatory and effector T cells due to IL-2 deprivation amplifies murine lupus

The origins and consequences of a regulatory T cell (Treg) disorder in systemic lupus erythematosus (SLE) are poorly understood. In the (NZBxNZW) F(1) mouse model of lupus, we found that CD4(+)Foxp3(+) Treg failed to maintain a competitive pool size in the peripheral lymphoid organs resulting in a progressive homeostatic imbalance of CD4(+)Foxp3(+) Treg and CD4(+)Foxp3(-) conventional T cells (Tcon). In addition, Treg acquired phenotypic changes that are reminiscent of IL-2 deficiency concomitantly to a progressive decline in IL-2-producing Tcon and an increase in activated, IFN-gamma-producing effector Tcon. Nonetheless, Treg from lupus-prone mice were functionally intact and capable to influence the course of disease. Systemic reduction of IL-2 levels early in disease promoted Tcon hyperactivity, induced the imbalance of Treg and effector Tcon, and strongly accelerated disease progression. In contrast, administration of IL-2 partially restored the balance of Treg and effector Tcon by promoting the homeostatic proliferation of endogenous Treg and impeded the progression of established disease. Thus, an acquired and self-amplifying disruption of the Treg-IL-2 axis contributed essentially to Tcon hyperactivity and the development of murine lupus. The reversibility of this homeostatic Treg disorder provides promising approaches for the treatment of SLE.

Chorea as a rare symptom of systemic lupus erythematosus in the elderly

The opinion that systemic lupus erythematosus (SLE) is a young people disease translates into its rare diagnosing in subjects in their 6th decade of life and older. The variability of neuropsychiatric disorders that may be the first symptoms of the disease suggest the need for their in-depth diagnostics and treatment. Chorea is one of the rarest neuropsychiatric symptoms of SLE. It may be present in an early stage of the disease and it is one of the most common motor disorders in SLE. The presented case of diagnosing SLE in a 79-year-old male shows the importance of individual and thorough assessment of the clinical picture of every patient regardless of his/her age and gender. In the discussed case the clinical course of the disease denies common opinions about the picture of SLE in the elderly.

Successful treatment of amegakaryocytic thrombocytopenia with anti-CD20 antibody (rituximab) in a patient with systemic lupus erythematosus

Amegakaryocytic thrombocytopenia is an extremely rare disorder in systemic lupus erythematosus, and its mechanism and treatment are still largely unknown. We describe a 42-year-old woman with systemic lupus erythematosus who presented various clinical manifestations of life-threatening amegakaryocytic thrombocytopenia (10,000 platelets/mm3 with a marked decrease of megakaryocytes in the bone marrow), proteinuria, psychosis, refractory chylothorax, ascites, and type II diabetes caused by the anti-insulin receptor autoantibody. She was initially treated with prednisolone (25-50 mg/day) and cyclosporine A (200 mg/day) without any improvement in severe thrombocytopenia. However, her clinical symptoms, including platelet counts, dramatically improved, with a concurrent decrease in the anti-c-Mpl antibody, an autoantibody against the thrombopoietin receptor, after a subsequent treatment with rituximab (375 mg/m2 intravenously, weekly, for two consecutive weeks). Our case suggested that amegakaryocytic thrombocytopenia in patients with systemic lupus erythematosus might be mediated by the anti-c-Mpl antibody and could be treated with rituximab through elimination of pathogenic B cells producing autoimmune antibodies.

The PPARgamma Agonist Rosiglitazone Decreases Blood Pressure and Renal Injury in a Female Mouse Model of Systemic Lupus Erythematosus

Women with the inflammatory autoimmune disorder systemic lupus erythematosus (SLE) exhibit a high incidence of hypertension and renal injury. Peroxisome proliferator activated receptor gamma (PPARγ) activation has anti‐inflammatory and anti‐hypertensive effects. We tested whether the PPARγ agonist rosiglitazone (Rosi) prevents hypertension and renal injury in a female mouse model of SLE (NZBWF1). 30 week old SLE and control (NZW/LacJ) mice (n≥ 7 per group) were fed either Rosi (5mg/kg/day in standard chow) or unsupplemented chow for 4 weeks. Renal injury was assessed using the glomerulosclerosis index (GSI) and a positive urinary albumin test ≥100 mg/dL, Albustix). MAP, measured by indwelling catheters, was increased in SLE mice compared to controls (139±4 vs. 112±4, p&lt;0.05). Rosi treatment significantly lowered MAP in SLE mice (127±4, p&lt;0.05) but had no effect in control mice (111±4 mmHg). Anti‐DNA auto‐antibodies, a marker for SLE, did not differ in vehicle or Rosi treated SLE mice (756±157 vs 762±251 ng/ml). Only 18% of Rosi treated SLE mice exhibited albuminuria compared to 42% of vehicle treated SLE mice. Mice with SLE had increased GSI compared with controls (1.9±0.6 vs 0.6±0.1, p&lt;0.05). Preliminary data indicate that GSI is reduced in Rosi treated SLE mice (1.0±0.2) with no effect in control mice (0.7±0.1). These data implicate PPARγ as a potential therapeutic target for the treatment hypertension and renal end‐organ damage associated with SLE. (supported by R01HL085907 MJR)

Blood-brain barrier damage as a risk factor for corticosteroid-induced psychiatric disorders in systemic lupus erythematosus

To clarify the incidence of and risk factors for corticosteroid-induced psychiatric disorders (CIPDs) in patients with systemic lupus erythematosus (SLE), we conducted a prospective study of 161 consecutive episodes in 155 inpatients with a SLE flare who were treated with corticosteroids. A subgroup of these patients, those who experienced a total of 22 episodes with current overt central nervous system manifestations of SLE (CNS-SLE), were excluded from follow-up. Results of clinical, laboratory, and neurologic tests (including electroencephalography, magnetic resonance imaging of the brain, and cerebrospinal fluid [CSF] analysis), performed within a week before corticosteroid administration, were assessed with regard to development of CIPDs. Within 8 weeks of corticosteroid administration, a diagnosis of CIPD was made for 14 (10.1%) of 139 episodes in 135 patients with a non-CNS-SLE flare. Using multiple logistic regression analysis, we identified positive Q(albumin) (CSF/serum albumin ratio; an indicator of blood-brain barrier [BBB] damage) (odds ratio [OR], 33.3; 95% confidence interval [CI], 3.64-304; p=0.002) and low serum levels of complements (OR, 0.91; 95% CI, 0.83-1.00; p=0.047) as independent risk factors for CIPDs. Positive Q(albumin) was detected in 45% (5 of 11) of episodes in which CIPDs developed. Compared with episodes in which no psychiatric events occurred, a higher level of Q(albumin) was found in episodes in which CIPDs developed, and an even higher level was noted in episodes with active CNS-SLE (Jonckheere-Terpstra test, p<0.001). Although no causal links have been proven, the results from the present study raise the possibility that BBB damage may be associated with SLE- and corticosteroid-induced behavioral changes.

Prevalence of depressive and anxiety disorders in systemic lupus erythematosus and their association with anti-ribosomal P antibodies

Objective To estimate the prevalence of psychiatric disorders in patients with systemic lupus erythematosus (SLE) and explore their association with anti-ribosomal P (anti-P) antibodies. Methods Seventy-one consecutive female SLE patients without neurological manifestations were evaluated for psychiatric disorders using the Structured Clinical Interview for DSM-IV (SCID). Anti-P antibodies were measured by enzyme-linked immunosorbent assay (ELISA)/immunoblot analysis. Results The mean age of subjects was 34.8 years (SD: 10.1 years), and the mean duration of SLE was 9.8 years (SD: 6.5 years). The 30-day prevalences of psychiatric disorders were: mood disorders 26.8%, anxiety disorders 46.5%, adjustment disorders 8.4%, alcohol abuse 1.4%, and somatoform disorder 1.4%. The lifetime prevalences of psychiatric disorders were: mood disorders 69%, anxiety disorders 52.1%, alcohol abuse 1.4%, and somatoform disorder 1.4%. Subjects with and without psychiatric manifestations did not differ regarding SLE clinical and laboratorial parameters including presence or absence of anti-P antibodies (23.1% vs. 20%, respectively, p = 1.0), disease activity, as measured by the Systemic Lupus Erythematosus Disease activity Index (4.08 ± 5.7 vs. 4.95 ± 6.3 respectively, p = 0.60) and cumulated damage, as measured by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (0.7 ± 2.3 vs. 0.3 ± 0.7 respectively, p = 0.33). Conclusions Mood and anxiety disorders are the most frequently observed psychiatric disorders in female SLE patients without concomitant neurological manifestations. These mild/moderate forms of psychiatric disorders are not associated with anti-P antibodies in SLE patients. Our findings reinforce the importance of systematic psychiatric evaluation for these patients in order to provide adequate and comprehensive care.

Reversible Posterior Leukoencephalopathy Syndrome Induced by Sunitinib

TO THE EDITOR: We would like to report the occurrence of reversible posterior leukoencephalopathy that we believe is directly attributable to sunitinib malate (Sutent; Pfizer Pharmaceuticals Group, New York, NY), a receptor tyrosine kinase inhibitor with antiangiogenic activity that is approved for the treatment of advanced renal cell carcinoma. A 70-year-old woman diagnosed with renal cell carcinoma and bone metastasis was first treated with palliative nefrectomy and interferon plus vinblastine. Afterwards, she was enrolled in a phase II clinical trial with sunitinib malate (50 mg daily for 4 weeks every 6 weeks). Two weeks after starting the treatment, she was admitted to the hospital because of partial seizures affecting her left superior extremity, headache, and vision loss in the previous 2 days. The physical examination was normal except for cortical blindness and hypertension (170/100 mmHg). Blood tests, including coagulation study and gasometry, were unremarkable. Computed tomography of the brain showed symmetric subcortical hypodense lesions in the occipital lobes, consistent with reversible posterior leukoencephalopathy syndrome (RPLS). Magnetic resonance imaging was requested to rule out brain micrometastasis and it confirmed the findings of RPLS: symmetric hyperintense T2 signal involving bilateral occipital and parietal lobes in the subcortical distribution (Fig 1). Sunitinib administration was withheld and the patient was treated with anticonvulsants and antihypertensives. She recovered completely, was discharged in a few days and had a normal brain computed tomography performed 1 month later. The RPLS was initially reported by Hinchey et al. It is a clinical condition characterized by headache, seizures, impaired vision, acute hypertension, and typical magnetic resonance imaging and computed tomography imaging findings (symmetric and reversible). This syndrome has been described related to different circumstances: hypertensive encephalopathy, eclampsia, collagen vascular disorders (systemic lupus erythematosus, polyarteritis nodose, Behcet), trombotic thrombocytopenic purpura, acute porphyria, postcarotid endarterectomy, and Guillain-Barre syndrome. However, it is most commonly caused by immunosuppressive agents and cytotoxic drugs as cyclosporine A, tacrolimus, interferon alfa, cisplatin, cytarabine, IV immunoglobulins, L-asparaginase, and more recently by bevacizumab (antiangiogenic agent) and sorafenib (tyrosine kinase inhibitor). Its pathogenesis is not precisely known. It is postulated that the alterations can be related with the appearance of vasogenic edema because of elevation in the blood pressure (vasospasm) or because of toxic damage to blood-brain barrier or vascular endothelium. Sunitinib has a dual activity: extracellular action against vascular endothelial growth factor receptor (antiangiogenic) and intracellular action against tyrosine kinase domains, which can produce hypertension. In our case, the set of symptoms could be caused through both mechanisms.

Electric charge and sugar chains of immunoglobulin G in systemic lupus erythematosus

The charge condition of anti-DNA antibody is thought to be closely related to the pathology of renal disorders in systemic lupus erythematosus (SLE). We examined the relationships among the electric charge of IgG, proteinuria, and DNA binding capacity in SLE patients. Abnormal sugar chains, which affect the IgG charge, were also studied. IgG in SLE patients with proteinuria had a higher positive electric charge than that in SLE patients without proteinuria, healthy individuals, and patients with other collagen diseases. Anti-DNA antibody titers measured by enzyme-linked immunosorbent assay (ELISA) were high in the positive charge regions of the IgG fractions obtained by a cationic exchange column. The binding capacity of double-stranded (ds)DNA measured by the Farr assay tended to be present specifically in the positive charge region in SLE patients with proteinuria. In affinoblotting using lectins, the percentage of IgG deficient in negative-charged sugar chains was found to be high in patients with a preponderant positive charge on anti-DNA antibody. Abnormal IgG-bound sugar chains result in a preponderantly positive charge and are involved in the etiology of SLE nephritis.

Hormonal Regulation of B Cell Development: 17β-Estradiol Impairs Negative Selection of High-Affinity DNA-Reactive B Cells at More Than One Developmental Checkpoint

There are increasing data suggesting that sex hormones, such as estrogen, have immunomodulatory effects and play a role in disease progression and pathogenesis in patients with the autoimmune disorder systemic lupus erythematosus. We have shown previously that treatment with 17beta-estradiol (E2) induces a lupus phenotype in BALB/c mice that express a transgene-encoded H chain of an anti-DNA Ab. Because E2 treatment interferes with normal tolerance of naive DNA-reactive B cells, we elected to study the effects of hormonal modulation on the regulation of autoreactive B cells at early developmental checkpoints. Single-cell PCR was performed to study the repertoire of DNA-reactive B cell subsets. High-affinity DNA-reactive B cells were rescued at both the immature and transitional B cell stage in E2-treated mice. Interestingly, although low-affinity DNA-reactive B cells survive negative selection in control mice, the frequency of these cells was significantly reduced in the mature pool of E2-treated mice, suggesting that the high-affinity DNA-reactive cells that mature to immunocompetence out-compete the low-affinity population for survival as mature B cells. These data provide evidence that an elevation in serum levels of E2 facilitates the maturation of a pathogenic naive autoreactive B cell repertoire and hampers the maturation of a potentially protective autoreactive B cell repertoire. Furthermore, these data show that both positive and negative selection occur within the transitional B cell stage.

Alterações da personalidade no lúpus eritematoso sistêmico

O lúpus eritematoso sistêmico (LES) é uma doença auto-imune de natureza crônica e multissistêmica, podendo afetar de forma importante o sistema nervoso central (SNC). Embora bastante freqüentes, as alterações de personalidade ainda não foram bem estudadas nessa população. Este é o principal objeto de estudo deste artigo de revisão, que verificou a divergência entre os autores quanto à importância dos traços de personalidade e suas alterações no desencadeamento e evolução da doença lúpica. Há controvérsia, ainda, sobre a etiologia das alterações de personalidade no LES, questionando-se se estas ocorreriam pelo estresse psicológico imposto pela patologia, pela atividade da doença no SNC, ou, ainda, pelo uso de medicamentos, como os glicocorticóides. Há necessidade, portanto, de novos estudos que venham a elucidar estas questões.

A Preterm Infant Who Has Acute Respiratory Decompensation

A 4-day-old preterm male infant presents with respiratory failure requiring 100% oxygen on assisted ventilation. ### Prenatal History: ### Birth History and Presentation: The infant was delivered by the vaginal route in vertex presentation. He had initial poor respiratory effort, but responded to warming, stimulation, and blow-by oxygen. Apgar scores were 7 at 1 minute and 8 at 5 minutes. He continued to demonstrate increased work of breathing and was intubated in the delivery room. He was admitted to the neonatal intensive care unit (NICU) for prematurity and respiratory distress. His birthweight was 1,589 g, which was appropriate for gestational age. Thirty minutes after birth, the patient had worsening tachypnea and subcostal retractions; chest radiograph at this time demonstrated diffuse bilateral reticular granular densities and microatelectasis CXR 1 . Oxygen saturation in room air was 78%. When 100% oxygen was administered, the oxygen saturation increased to 92%. Arterial blood gas (ABG) revealed: What is the appropriate treatment of this infant at this time? On arrival to the NICU, the patient was intubated and placed on mechanical ventilation. An echocardiogram revealed normal cardiac structure and function. The blood lactate level was elevated at 225.2 mg/dL (25 mmol/L). Blood ammonia concentration also was elevated at 518 mmol/L. Ketones were noted in the urine. ### Vital Signs Were: ### Physical Examination

Pregnancy Outcome in Lupus Nephropathy

The autoimmune disorder systemic lupus erythematosus (SLE) chiefly affects women of childbearing age. Reported incidence figures range from 1 in 660 to 1 in 2952 deliveries. The clinical course of SLE in pregnant women isunpredictable, but the effects of lupus nephritis (LN) on fetal outcomes remain uncertain. The investigators examined maternal and fetal outcomes in 24 patients with LN who had 55 pregnancies over a 15-year period. All the women met American College of Rheumatology revised criteria for SLE and had clinical evidence of LN (proteinuria, nephrotic syndrome, renal insufficiency). Ten had longstanding LN. There were 36 pregnancies in 16 patients in remission (group A) and 19 pregnancies in 8 women with clinically active renal disease at the time of birth (group B). First-trimester spontaneous abortion occurred in 9 group A women (25%). There were 25 live births and 2 stillbirths. More than one fifth of the deliveries were preterm births. Complications included intrauterine growth retardation (11%), pregnancy-induced hypertension in 18.5%, and premature rupture of membranes in 7.4% of group A cases. Eleven of 36 pregnancies resulted in spontaneous term delivery. Approximately one third of group B pregnancies ended in spontaneous abortion. Three of 13 viable deliveries were uncomplicated term births. Chronic hypertension complicated 6 of the 19 group B pregnancies. Four cesarean sections were carried out. There were 3 spontaneous preterm deliveries. Three group B pregnancies were complicated by intrauterine growth retardation; all these mothers were hypertensive. Three stillbirths occurred, and there was I early neonatal death. Overall perinatal mortality was 150 per 1000 deliveries. The mean gestational age of live-born infants in this study was 33.5 weeks, and the mean birth weight was 2.5 kg. Two women had irreversible deterioration of renal function and died. A postpartum flare of clinical LN occurred in 3 group A and 3 group B cases. Two of these 6 women required high-dose steroid therapy. Pregnant women with LN are at high risk of complicated pregnancies and adverse outcomes. Ideally, a rheumatologist and obstetrician/perinatologist who have experience with SLE in pregnancy will follow these patients. Much better outcomes may be expected if LN is controlled before conception.

Autoantibody profile in systemic lupus erythematosus with psychiatric manifestations: a role for anti-endothelial-cell antibodies

This study was performed to determine the correlation between psychiatric manifestations and several autoantibodies that might participate in the pathogenesis of psychiatric disorders in the course of systemic lupus erythematosus (SLE). Fifty-one unselected outpatients with SLE were enrolled. Psychiatric evaluation was performed according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. The prevalence of antibodies against endothelial cells (AECA), cardiolipin, β2 glycoprotein I, Ro, Ro52, La, glial fibrillary acidic protein, ribosomal P protein, dsDNA, and nucleosomes was assessed by experimental and commercial enzyme-linked immunosorbent assays. According to the cutoff value, AECA were present in 11 of 17 (64.7%) SLE patients with psychosis and mood disorders and in 10 of 34 (29.4%) patients without psychiatric manifestations other than anxiety (P = 0.03). Moreover, the AECA binding index was significantly higher in the first group (P = 0.03). Conversely, no significant correlation was found between the presence of the other autoantibodies studied and psychiatric involvement. The results of this study suggest a relationship between AECA and psychosis and mood disorders in SLE, supporting the hypothesis of a biological origin of these disturbances.