Frequency of anti-neutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus / Frecuencia de los anticuerpos anticitoplasma de neutrófilo en pacientes con lupus eritematoso sistémico

ABSTRACT Introduction: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease. Patients with SLE exhibit multiple serum autoantibodies, including anti-neutrophil cytoplasmic antibodies (ANCAs). There are two main techniques to detect ANCAs: indirect immunofluorescence (IIF) and enzyme-linked immunosorbent assay (ELISA). In this study, an attempt was made to determine the frequency and clinical associations of ANCAs in patients with SLE. Methods: A cross-sectional study was conducted in a tertiary care hospital in Colombia that included 74 patients with SLE. The presence of ANCAs was assessed using IIF with ethanol-fixed slides, and ELISA was used to detect antibody specificities for myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA. Results: Of the 74 patients with SLE evaluated, 60 (81.1%) of them were ANCA-positive by IIF. By contrast, only one patient showed specificity for PR3-ANCA by ELISA. The relevance of ANCA positivity by IIF and clinical and serological features was significant for renal involvement (p = .0174), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) (p = .0308). Conclusion: ANCAs are common in the serum of patients with SLE, as detected by ethanol-fixed slides with IIF staining. However, detection of specificity to PR3 and/or MPO is rare, thus highlighting the importance of detecting these autoantibodies by different techniques.

RESUMEN Introducción: El lupus eritematoso sistémico (LES) es una enfermedad autoinmune sistémica. Los pacientes con LES muestran múltiples autoanticuerpos séricos, incluyendo los anticuerpos anticitoplasma de neutrófilo (ANCA, por sus siglas en inglés). Existen 2 técnicas principales para la detección de ANCA: inmunofluorescencia indirecta (IFI) y ensayo por inmunoadsorción ligado a enzimas (ELISA). En este estudio nuestro objetivo fue determinar la frecuencia y las asociaciones clínicas de los ANCA en pacientes con LES. Métodos: Realizamos un estudio transversal de 74 pacientes con LES en un hospital de alta complejidad de Colombia. La presencia de ANCA se evaluó por IFI, utilizando láminas con fijación de etanol, y con ELISA para determinar las especificidades para mieloperoxidasa (MPO)-ANCA y proteinasa 3 (PR3)-ANCA. Resultados: Fueron evaluados 74 pacientes con LES, 60 (81,1%) de ellos fueron positivos para ANCA. Por el contrario, solo un paciente mostró especificidad para PR3-ANCA por ELISA. La relación entre la positividad para ANCA por IFI y las características clínicas y serológicas fue estadísticamente significativa para compromiso renal (p = 0,0174) y para el índice de actividad de la enfermedad (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI]) (p = 0,0308). Conclusiones: Los ANCA detectados mediante fijación con etanol por técnicas de IFI, son comunes en pacientes con LES. Sin embargo, la detección de especificidades para PR3 o MPO es rara; se destaca la importancia de la evaluación de estos autoanticuerpos mediante diferentes técnicas.

Systemic erythematosus lupus and pregnancy outcomes in a Colombian cohort.

OBJECTIVE: Pregnant women with SLE have higher probabilities of maternal complications. SLE during pregnancy has alternating patterns of remission and flare-ups; however, most pregnant SLE patients tend to worsen with associated poor obstetric and perinatal outcomes. This study aimed to describe obstetric outcomes in pregnant women with SLE. METHODS: This retrospective study was performed between 2011 and 2020 at a highly complex referral health center in Cali, Colombia. Pregnant women with a diagnosis of SLE were included. Demographic, clinical, and laboratory features and obstetric and fetal outcomes, including intensive care unit (ICU) characteristics, were evaluated. RESULTS: Forty-eight pregnant women with SLE were included. The median age was 29 (25-33.7) years. The SLE diagnosis was made before pregnancy in 38 (79.1%) patients, with a median disease duration of 46 (12-84) months. Thirteen (27.1%) patients had lupus nephritis. Preterm labor (34, 70.8%), preeclampsia (25, 52%), and preterm rupture of membranes (10, 20.8%) were the most common obstetric complications. A relationship between a greater systemic lupus erythematosus pregnancy disease activity index (SLEPDAI) and the development of hypertensive disorders during pregnancy was established (preeclampsia = p < 0.0366; eclampsia = p < 0.0153). A relationship was identified between lupus nephritis (LN) and eclampsia (p < 0.01), preterm labor (p < 0.045), and placental abruption (p < 0.01). Seventeen (35.4%) patients required ICU admission; 52.9% of them were due to AID activity, 17.6% for cardiovascular damage, 11.7% for septic shock, and 5.8% for acute kidney failure. Fetal survival was 89.5% (N = 43/48). Among the live births, two (4.2%) newborns were diagnosed with neonatal lupus, and two (4.2%) were diagnosed with congenital heart block. One maternal death was registered due to preeclampsia and intraventricular hemorrhage. CONCLUSIONS: This study is the first to describe SLE during pregnancy in Colombia. SLE was the most prevalent AID in this cohort, and complications included preterm labor, preeclampsia, and postpartum hemorrhage. A higher SLEPDAI and lupus nephritis predicted adverse maternal outcomes.

Caracterización epidemiológica de pacientes con miopatía inflamatoria en un hospital de cuarto nivel en Cali, Colombia / Epidemiological characterization of patients with inflammatory myopathy in a fourth level hospital in Cali, Colombia

Introducción: Las miopatías inflamatorias idiopáticas (MII) constituyen un grupo heterogéneo de enfermedades que comprometen la musculatura esquelética y se manifiestan por debilidad y signos inflamatorios en la biopsia muscular. El objetivo de este estudio es hacer una caracterización epidemiológica de una cohorte de pacientes con MII en una población del suroccidente colombiano. Metodología: De forma retrospectiva, se revisaron las historias clínicas de pacientes con diagnóstico de MII que fueron tratados en un hospital de cuarto nivel de complejidad en Cali, Colombia, entre el 2011 y el 2017. Se recolectaron variables demográficas, clínicas, serológicas y de tratamiento. Resultados: Se identificaron 72 pacientes con MII, mayoritariamente mujeres (n = 54, 75%). La media de edad al inicio de los síntomas fue de 37,11 ± 19,18 años. Las principales MII fueron dermatomiositis (DM) y polimiositis, las cuales se presentaron en 35 (48,6%) y 25 pacientes (34,7%), respectivamente. Veintiocho pacientes (38,8%) presentaban enfermedad autoinmune asociada, siendo el lupus eritematoso sistémico la más frecuente, al presentarse en7 (9,72%) pacientes. La biopsia de músculo se realizó en 25 pacientes (34,7%), mientras que28 (38,8%) tenían anticuerpos antinucleares positivos. La mediana de la creatinfosfoquinasa fue de 877,5 mg/dL (163,5-4.358,3). Sesenta y siete pacientes (93,1%) fueron tratados con glucocorticoides y 18 (25%) con rituximab (RTX) como monoterapia o combinado con otro fármaco inmunosupresor. Conclusiones: La DM es la condición clínica más frecuente, es común en mujeres y se presenta en la cuarta década de vida. Los tratamientos con los que más se obtuvo mejoría clínica fueron los glucocorticoides, seguidos del RTX en monoterapia o combinado con otros inmunosupresores.

Background: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of diseases characterised by skeletal muscle involvement, manifested by weakness and inflammatory signs in the muscle biopsy. The objective of this article is to describe the clinical, laboratory, and treatment features of a cohort of patients with IIM in southwest Colombia. Methods: A retrospective review was conducted on the medical records of patients diagnosed with IIM treated at a fourth-level complexity hospital in Cali, Colombia, from 2011 to 2017. Demographic, clinical, serological, and treatment data were collected. Results: A total of 72 patients with IIM were identified, mostly women (n = 54,75%). The mean age at onset of symptoms was 37.11 ± 19.18 years. The main subtypes of IIM were dermatomyositis (DM) and polymyositis, occurring in 35 patients (48.6%) and 25 patients (34.7%), respectively. Twenty-eight patients (38.8%) had associated autoimmune disease, with syste mic lupus erythematosus being the most frequent in 7 (9.72%) patients. Muscle biopsy was performed in 25 patients (34.7%), while 28 (38.8%) had positive antinuclear antibodies. The median creatine phosphokinase was 877.5 mg/dL (163.5-4358.3). Sixty-seven patients (93.1%) were treated with glucocorticoids, and 18 (25%) patients were treated with rituximab (RTX) as monotherapy or combined with another immunosuppressant drug. Conclusions: DM is the most frequent subtype of IIM, being common in women and occurring in the fourth decade of life. The most used treatments were glucocorticoids, followed by RTX monotherapy, or combined with other immunosuppressants.

Utility of anti-C1q and anti-nucleosome antibodies in systemic lupus erythematosus and lupus nephritis in southwestern Colombia / Utilidad de los anticuerpos anti-C1q y anti-nucleosomas en el lupus eritematoso sistémico y la nefritis lúpica en el suroccidente colombiano

ABSTRACT Introduction: Lupus nephritis (LN) is one of the most prevalent and severe complications of systemic lupus erythematosus (SLE), requiring reliable urine and serum biomarkers to evaluate it. Anti-nucleosome and anti-C1q antibodies are associated with LN in several geographic regions. Also, southwest Colombia has a heterogeneous ethnicity, which motivated the evaluation of the frequency and relationship of such markers with LN in this region. Methods: A cross-sectional study was conducted in a health centre in south-west Colombia in 84 patients diagnosed with SLE (57 without LN; 27 with LN) between 2016 and 2018. Demographic and clinical and laboratory features, including anti-dsDNA, complement, and anti-C1q and anti-nucleosome antibodies were compared in these patients. ELISA immunoassays were performed to measure the antibodies of interest in blood samples. Statistical analysis was carried out using STATA14 software (StataCorp, College Station, Texas, USA). Quantitative variables were summarised as means or medians and compared with Mann-Whitney or Two-sample t test. Categorical variables were shown as proportions, and compared with Chi-squared or Fisher's exact test. Correlation analysis between quantitative variables was calculated using Spearman's correlation. Results: Of all 84 patients, 27 patients had LN, of which 16 (59.2%) had a positive test for anti-nucleosome antibodies and 10 (37%) for anti-C1q antibodies. An association was found between anti-C1q and proliferative forms of LN and newly diagnosed LN. A correlation was found between anti-nucleosome and anti-C1q antibodies, and anti-dsDNA and low serum complement concentrations. Conclusion: Although both markers were found in variable percentages in SLE patients and seem not to be specific markers of LN in our population, anti-C1q was associated with proliferative forms of LN and de novo LN.

RESUMEN Introducción: La nefritis lúpica (NL), una de las complicaciones más frecuentes y graves del lupus eritematoso sistémico (LES), requiere biomarcadores confiables de orina y suero para su evaluación. Los anticuerpos anti-nucleosoma y anti-C1q se asocian con la NL en varias regiones geográficas. En el suroccidente colombiano se asienta una etnia heterogénea, lo que motivó la evaluación de la frecuencia y la relación de dichos marcadores con NL en dicha región. Métodos: Realizamos un estudio transversal en un centro de salud en el suroccidente de Colombia, con 84 pacientes diagnosticados con LES (57 sin NL; 27 con NL) entre los anos 2016 y 2018. Se compararon las características demográficas, clínicas y de laboratorio, incluidos los anticuerpos anti-dsDNA, complemento, anti-C1q y anti-nucleosomas entre estos pacientes. Se realizaron inmunoensayos ELISA para medir los anticuerpos de interés en muestras de sangre. El análisis estadístico se llevó a cabo con el software Stata v.14 (Stata-Corp, College Station, Texas, EE. UU.). Las variables cuantitativas se resumieron como medias o medianas y se compararon con la prueba t de Mann-Whitney o Two-sample t test; las variables categóricas se mostraron como proporciones y se compararon con Chi-cuadrado o con la prueba exacta de Fisher. Para el análisis de correlaciones entre variables cuantitativas se calculó el coeficiente de correlación de Spearman. Resultados: Entre los 84 pacientes, 27 presentaban LN, de los cuales 16 (59,2%) tuvieron una prueba positiva para anticuerpos anti-nucleosoma y 10 (37%) para anticuerpos anti-C1q. Se encontró una asociación entre anti-C1q y formas proliferativas de NL, así como formas recientemente diagnosticadas de NL. Hubo una correlación entre los anticuerpos anti-nucleosoma y anti-C1q y el anti-dsDNA y las bajas concentraciones de complemento sérico. Conclusión: Aunque los 2 marcadores se encontraron en porcentajes variables de pacientes con LES y no parecen ser marcadores específicos de NL en nuestra población, la presencia de anti-C1q se asoció con formas proliferativas de NL y NL de novo.

Rituximab for Inflammatory Myopathies in a Colombian Cohort.

INTRODUCTION/OBJECTIVES: Rituximab (RTX) is a treatment for refractory inflammatory myopathies, such as dermatomyositis (DM) and polymyositis (PM). This study describes the characteristics of patients receiving RTX for myositis in our institution to evaluate its efficacy. METHOD: We collected demographic data from all patients diagnosed with DM or PM who received RTX between 2011 and 2018. Clinical and serological variables (including creatine phosphokinase [CPK] levels) were analyzed. Remission of disease was defined as no evidence of disease activity (active myositis) for longer than a 6-month continuous period while undergoing myositis therapy or no medication. RESULTS: Eighteen patients who had received first-line immunosuppressants were included. Fifteen (83%) had DM, 2 (11%) had PM, 1 had juvenile dermatomyositis, and 14 (77%) were women. All patients received glucocorticoids. Three patients (16.6%) were treated with RTX as monotherapy, and 15 (83.3%) were treated with RTX combined with other immunosuppressants. On average, there were 2 RTX treatment cycles. Improved muscular weakness was found in 13 cases (72%), and improved serum CPK levels were found in 15 cases (83%). Twelve patients (66%) achieved remission. CONCLUSIONS: Most patients experienced an objective improvement, as reflected in their serum CPK values and degree of muscular weakness. This suggests that RTX could be helpful in treating refractory myositis.

Cathelicidin LL-37: A new important molecule in the pathophysiology of systemic lupus erythematosus.

Cathelicidin LL-37 is an antimicrobial peptide that is synthesized by epithelial cells, neutrophils, or lymphocytes and act as an essential defense mechanism against bacterial, viral, or fungi infection of eukaryotic organisms. However, in recent years, this cathelicidin has gained the interest of the scientific community because, besides its antimicrobial properties, LL-37 is an immunomodulator that can contribute to the development of autoimmune diseases. The other non-antimicrobial function of this cathelicidin is its ability to form complexes with the DNA, stimulating plasmacytoid dendritic cells (pDCs) to produce type I IFN, deciding the course of autoimmune diseases, including systemic lupus erythematosus (SLE). The chronic activation of pDCs by surrounding complexes is a crucial factor for the early development of autoimmunity in SLE patients. This stimulation is given by the complexes (LL-37-DNA/anti-DNA) recognized by the receptor FcγRII on pDCs, allowing its endocytosis and its recognition via TLR9, leading to the activation of pDCs and enhanced type I IFN production. In this article, we reviewed the structure, function, and importance of LL-37 in innate immunity, as well as its biological plausibility in the pathophysiology of autoimmune diseases such as SLE. In this narrative review, we included primary journal articles describing the function, structure, prevalence, and importance of LL-37 in various manifestations of SLE, as well as LL-37 and anti-LL37 antibodies in patients with SLE or other autoimmune diseases. In conclusion, LL-37 is an essential molecule in the pathophysiology of SLE, mainly by its role in increasing the production of IFN by pDCs, which postulates it as a crucial molecule in the pathophysiology of SLE and, given plausibility biology, could serve as a biomarker of the disease.

Urinary biomarkers in lupus nephritis.

Systemic lupus erythematosus (SLE) is the prototypical autoimmune disease that can affect any organ of the body. Multiple mechanisms may contribute to the pathophysiology of systemic lupus, including failure to remove apoptotic bodies, hyperactivity of self-reactive B and T lymphocytes, abnormal exposure to autoantigens, and increased levels of B-cell stimulatory cytokines. The involvement of the kidney, called lupus nephritis (LN), during the course of the disease affects between 30% and 60% of adult SLE patients, and up to 70% of children. LN is an immune-mediated glomerulonephritis that is a common and serious finding in patients with SLE. Nowadays, renal biopsy is considered the gold standard for classifying LN, besides its degree of activity or chronicity. Nevertheless, renal biopsy lacks the ability to predict which patients will respond to immunosuppressive therapy and is a costly and risky procedure that is not practical in the monitoring of LN because serial repetitions would be necessary. Consequently, many serum and urinary biomarkers have been studied in SLE patients for the complementary study of LN, existing conventional biomarkers like proteinuria, protein/creatinine ratio in spot urine, 24 â€‹h urine proteinuria, creatinine clearance, among others and non-conventional biomarkers, like Monocyte chemoattractant protein-1 (MCP-1), have been correlated with the histological findings of the different types of LN. In this article, we review the advances in lupus nephritis urinary biomarkers. Such markers ideally should be capable of predicting early sub-clinical flares and could be used to follow response to therapy. In addition, some of these markers have been found to be involved in the pathogenesis of lupus nephritis.

Therapeutic Plasma Exchange as a Treatment for Autoimmune Neurological Disease.

INTRODUCTION: Therapeutic plasma exchange (TPE) is commonly used as treatment of certain autoimmune neurological diseases (ANDs), and its main objective is the removal of pathogenic autoantibodies. Our aim was to describe the clinical profile and the experience with the usage of TPE in patients with ANDs at our institution. METHODS: This is an observational retrospective study, including medical records of patients with diagnosis of ANDs who received TPE, between 2011 and 2018. Characteristics of TPE, such as number of cycles, type of replacement solution, and adverse effects, were evaluated. The modified Rankin Scale (mRS) was applied to measure the clinical response after the therapy. RESULTS: 187 patients were included with the following diagnoses: myasthenia gravis (MG), n = 70 (37%); Guillain-Barré syndrome (GBS), n = 53 (28.3%), neuromyelitis optica spectrum disorders (NMOSD), n = 35 (18.7%); chronic inflammatory demyelinating polyneuropathy (CIDP), n = 23 (12.2%); and autoimmune encephalitis (AE), n = 6 (3.2%). The most used types of replacement solution were albumin (n = 131, 70%) and succinylated gelatin (n = 45, 24%). All patients received a median of five cycles (IQR 5-5). Hypotension and hydroelectrolytic disorders were the main complications. After TPE, 99 patients (52.9%) showed improvement in the mRS scores and a statistical significance (p < 0.05) was seen between the admission score and after TPE for every diagnosis except for CIDP. CONCLUSION: TPE has an adequate safety profile, and improvement in functionality in treated patients reflects its effectiveness.

Systemic lupus erythematosus in the intensive care unit: a systematic review.

Systemic lupus erythematosus (SLE) is an autoimmune disease with heterogeneous pathophysiologic mechanisms and diverse clinical manifestations. SLE is a frequent cause of intensive care unit (ICU) admissions. Multiple studies with controversial findings on the causes, evolution and outcomes of ICU-admitted patients with SLE have been published. The aim of this paper is to review the literature reporting the clinical characteristics and outcomes, such as mortality and associated factors, in such patients. Among the main causes of ICU admissions are SLE disease activity, respiratory failure, multi-organ failure and infections. The main factors associated with mortality are a high Acute Physiology and Chronic Health Evaluation (APACHE) score, the need for mechanical ventilation, and vasoactive and inotropic agent use. Reported mortality rates are 18.4%-78.5%. Therefore, it is important to evaluate SLE disease severity for optimizing clinical management and patient outcomes.

Clinical characterization, outcomes, and prognosis in patients with systemic lupus erythematosus admitted to the intensive care unit.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically heterogeneous autoimmune disease, and in some conditions, admission to the intensive care unit (ICUs) is required. This study describes the clinical and prognostic factors in SLE patients admitted to the ICU. METHODS: We conducted a retrospective study that reviewed all clinical records of patients with SLE admitted to the ICU between 2011 and 2018. RESULTS: We evaluated 188 patients, with 279 ICU admissions. Most patients were female (n = 159; 84.57%) with a median age of 35 years (interquartile range (IQR) = 25-48 years). Infection was the leading cause of admission in 77 (27.60%) cases, followed by lupus flare. The average length of hospitalization was 5 days (IQR 3-11 days), and the SLE Disease Activity Index 2000, Acute Physiology, Age and Chronic Health Evaluation (APACHE II), and Sequential Organ Failure Assessment (SOFA) scores were 9 (IQR 2-17), 14 (IQR 10-17), and 3 (IQR 2-5), respectively. Non-survivors presented with higher APACHE II and SOFA scores. Infection was the leading cause of mortality (n = 38; 20.21%), and predictors of mortality included invasive mechanical ventilation, vasoactive medication requirement, higher SOFA scores, and antiphospholipid syndrome comorbidity. CONCLUSIONS: We found that infection was the leading cause of ICU admissions and mortality in patients with SLE. Factors identified here as predictors of mortality should be accurately identified at admission for the prompt treatment of SLE patients.

Prevalence of anti-DFS70 autoantibodies in a Latin American cohort of patients with systemic lupus erythematosus and without autoimmune diseases.

INTRODUCTION/OBJECTIVES: Anti-dense fine speckled 70 (DFS70) autoantibodies were reported to be more prevalent in healthy individuals than those with autoimmune diseases such as systemic lupus erythematosus (SLE). We determined anti-DFS70 autoantibody prevalence in a Latin American cohort of patients with SLE and healthy individuals. METHODS: This study included 127 individuals with anti-nuclear antibodies (ANAs; > 1:160) suggesting the presence of anti-DFS70, including 64 patients with SLE and 63 healthy controls. The anti-DFS70 autoantibodies were determined by immunoadsorption using NOVA Lite® HEp-2 Select kit with DAPI. Negative fluorescence after adsorption with the DFS70 antigen indicated anti-DFS70 autoantibody positivity. RESULTS: The presence of anti-DFS70 autoantibodies was confirmed by indirect immunofluorescence in 21 (33.3%) healthy controls and 8 (12.5%) patients with SLE (p = 0.005). Among the anti-DFS70-positive patients with SLE, the most frequent compromise was renal involvement in six cases (75%), 4 patients (37.5%) were positive for anti-Sm, which was the most frequently associated antibody, and one patient (12.5%) was positive for anti-DNA. CONCLUSIONS: Anti-DFS70 autoantibodies might be considered a biomarker to differentiate patients with SLE from ANA-positive individuals without autoimmune diseases. KEY POINTS: • In a Latin American cohort, the anti-DFS70 was higher in individuals without autoimmune diseases compared with that in patients with SLE.• The anti-DFS70 might have utility as a biomarker of exclusion in patients with non-specific clinical signs of AARDs.

Sjögren Syndrome in the Intensive Care Unit: An Observational Study.

BACKGROUND/OBJECTIVE: Studies on the clinical characteristics, prognosis, and factors associated with mortality in patients with Sjögren syndrome (SS), particularly those in the intensive care unit (ICU), are limited. The present study aimed to describe clinical and immunological variables associated with mortality in patients with SS admitted to ICU at a single center in Cali, Colombia. METHODS: An observational, medical records review study was performed between 2011 and 2019 by reviewing the clinical records of patients with SS admitted to ICU at a high-complexity center. RESULTS: Seventy-two patients were included with a total of 117 ICU admissions (17 cases required readmission and 1 case required 17 readmissions): 103 (86.32%) were attributable to medical issues, and 14 corresponded to surgical admissions. Major causes of ICU medical admission were infection (44/103) followed by organ involvement. Only 5 admissions were related to SS due to neurological involvement. The APACHE (Acute Physiology, Age, and Chronic Health Evaluation) score was 10 (interquartile range [IQR], 7-16), the SOFA (Sequential Organ Failure Assessment) score was 2 (IQR, 0-14), and the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score was 0 (IQR, 0-12) with higher values in the nonsurvivor group. Intensive care unit mortality was 12/72 (16.67%). CONCLUSIONS: The main cause of ICU admission was infection. Patients with increased medical requirements, such as mechanical ventilation and vasopressor support, and with higher APACHE, SOFA, and ESSDAI scores were more susceptible to poor outcomes. Moreover, 50% of deaths were attributable to SS and 25% to infection.

Diffuse Alveolar Hemorrhage: A Cohort of Patients With Systemic Lupus Erythematosus.

BACKGROUND/OBJECTIVE: Diffuse alveolar hemorrhage (DAH) is an uncommon but potentially fatal complication in patients with systemic lupus erythematosus (SLE). Its prognosis and factors associated with mortality are not completely clear, although invasive mechanical ventilation (IMV), use of cyclophosphamide, a high Acute Physiology and Chronic Health Evaluation II score, and infections are associated with high mortality rates. We investigated clinical and immunologic characteristics and factors associated with mortality in a cohort of Latin American patients with SLE who developed DAH. METHODS: A medical records review study was conducted of patients with SLE who were admitted to the intensive care unit (ICU) with DAH between 2011 and 2018. Clinical, laboratory, and treatment variables were compared between survivors and nonsurvivors. RESULTS: A total of 17 patients with SLE presented with DAH during the study period, of whom 11 (64.70%) were women. The median age was 28 (19-38.5) years. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) on admission to the ICU was 15.94 ± 10.07. All patients received pulse methylprednisolone and therapeutic plasma exchange, and 13 (76. %) also received cyclophosphamide. During the hospital stay, 5 patients (29.41%) died. A high SLEDAI on admission, low albumin, and days of IMV and inotropic/vasoactive support were statistically significant in comparing nonsurvivors with survivors. Other scales of disease severity commonly used in the ICU, however, were not significantly associated with a fatal outcome. CONCLUSIONS: Hypoalbuminemia, longer duration of IMV or inotropic/vasoactive treatment, and a high SLEDAI are potential prognostic factors for mortality in patients with SLE and DAH admitted to the ICU.

The role of high mobility proteins (HMGB1) in systemic lupus erythematosus / Papel de las proteínas de alta movilidad (HMGB1) en el lupus eritematoso sistémico

ABSTRACT Introduction: The high mobility group box 1 proteins (HMGB1) are non-histone nuclear proteins reported to be present at high levels in some autoimmune diseases, such as systemic lupus erythematosus (SLE). Likewise, in contrast to healthy individuals, patients with SLE have a higher prevalence of anti-HMGB1 antibodies, and these levels have also been associated with heightened disease activity. This article will discuss the involvement of these proteins in immunology, and review the evidence supporting their clinical importance in SLE. Materials and methods: A narrative review was conducted based on a search of the literature up to October 2018, of articles describing the function, structure, prevalence and importance of HMGB1 in different manifestations of SLE. Articles focusing on the presence of HMGB1 and/or its antibodies in patients with SLE or other autoimmune diseases were also reviewed. Results: A total of 69 articles were found. These articles were the foundation to define the structure and functions of HMBG1, including its role as a cytokine released by immune cells in inflammatory processes and necrosis. Additionally, a description of its functions in phagocytosis and NETosis - that have an impact on autoimmune diseases, primarily in SLE - was included. Conclusion: HMGB1 proteins and anti-HMGB1 antibodies are elevated in the serum of patients with SLE, in contrast with healthy individuals or non-severe presentations of the disease; this suggests that they may play a role as a biomarker of disease activity.

RESUMEN Introducción: Las high mobility group box 1 protein (HMGB1, «proteínas de alta movilidad del grupo 1¼) son proteínas nucleares no histonas cuyos niveles se han documentado elevados en ciertas enfermedades autoinmunes, como el lupus eritematoso sistémico (LES). Igualmente, los pacientes con LES presentan una mayor prevalencia de anticuerpos anti-HMGB1 comparados con individuos sanos, al mismo tiempo que se han relacionado sus niveles con una mayor actividad de la enfermedad. En este artículo se revisará la participación de estas proteínas en la inmunología y se abordará la evidencia que sustenta su importancia clínica en el LES. Materiales y métodos: Se realizó una revisión narrativa basada en la búsqueda de la literatura hasta octubre de 2018, de artículos que describieran la función, estructura, prevalencia e importancia de las HMGB1 en diferentes manifestaciones del LES, así como artículos que hayan estudiado la presencia de las HMGB1 o sus anticuerpos en pacientes con LES u otras enfermedades autoinmunes. Resultados: Se encontraron un total de 69 artículos. Con base en ellos definimos la estructura y funciones de las HMBG1, incluyendo su papel como citocina liberada por células inmunes en procesos inflamatorios y en necrosis. Adicionalmente, describimos sus funciones en la fagocitosis y NETosis, que genera implicaciones en enfermedades autoinmunes, principalmente en el LES. Conclusión: Las proteínas HMGB1 y los anticuerpos anti-HMGB1 se encuentran elevados en suero de pacientes con LES comparados con individuos sanos o con formas no severas de la enfermedad, evidenciando que estas pueden comportarse como un biomarcador de actividad de la enfermedad.

Frontal fibrosing alopecia: A new autoimmune entity?

Frontal fibrosing alopecia (FFA) is a rare type of cicatricial alopecic band, with bilateral and symmetric progressive regression of the frontotemporal hairline. The specific mechanisms of development of FFA remain unknown. Due to several clues, including the presence of lymphocytic infiltrates and the association of FFA with other autoimmune disorders, we hypothesised that FFA may be a new autoimmune condition, and future research must be focused on this possible origin.