Potential role for tissue factor in the pathogenesis of hypercoagulability associated with in COVID-19.

In December 2019, a new and highly contagious infectious disease emerged in Wuhan, China. The etiologic agent was identified as a novel coronavirus, now known as Severe Acute Syndrome Coronavirus-2 (SARS-CoV-2). Recent research has revealed that virus entry takes place upon the union of the virus S surface protein with the type I transmembrane metallo-carboxypeptidase, angiotensin converting enzyme 2 (ACE-2) identified on epithelial cells of the host respiratory tract. Virus triggers the synthesis and release of pro-inflammatory cytokines, including IL-6 and TNF-α and also promotes downregulation of ACE-2, which promotes a concomitant increase in levels of angiotensin II (AT-II). Both TNF-α and AT-II have been implicated in promoting overexpression of tissue factor (TF) in platelets and macrophages. Additionally, the generation of antiphospholipid antibodies associated with COVID-19 may also promote an increase in TF. TF may be a critical mediator associated with the development of thrombotic phenomena in COVID-19, and should be a target for future study.

Is Bariatric Surgery a Trigger Factor for Systemic Autoimmune Diseases?

Bariatric procedures are an effective option for weight loss and control of comorbidities in obese patients. Obesity is a proinflammatory condition in which some cytokines such as leptin, a proinflammatory protein, is elevated and adiponectin, an anti-inflammatory protein, is decreased. In patients undergoing weight reduction surgeries, these hormone levels behave paradoxically. It is not known whether bariatric surgery protects against development of autoinflammatory or autoimmune conditions; nevertheless, changes occurring in the immune system are incompletely understood. In this case series, we describe 4 patients undergoing bariatric surgery, who subsequently developed systemic autoimmune diseases. Patients in our case series were asymptomatic before surgery and developed an autoimmune disease within 11.2 months. Two women fulfilled criteria for systemic lupus erythematosus (one associated with antiphospholipid syndrome), and 2 men developed rheumatoid arthritis. A causal relationship is difficult to establish because factors that could trigger these diseases are multiple, including genetic susceptibility, time elapsed until achievement of ideal weight, and vitamin deficiencies, among others. However, clinicians must be attentive to this possible association.

Recovery of Severe Muscular and Fascial Calcinosis After Treatment With Bisphosphonates in a Child With Juvenile Dermatomyositis.

Juvenile dermatomyositis (JDM) is a serious systemic autoimmune condition primarily affecting proximal muscles and skin, which is frequently associated with calcinosis. We report a case of a 10-year-old boy with JDM and severe calcification deposits along fasciae and muscle planes. He complained of symptoms associated to JDM with pulmonary involvement since 1 year before receiving medical attention. Three months before consultation, he experienced bilateral leg pain accompanied by progressive hardening of muscles and the presence of small nodules around the elbows and submandibular region. Computed tomography images revealed a severe "eggshell" calcification pattern of the lower-limb muscular fasciae. Significant clinical and radiological improvement was achieved after 30 months of alendronate therapy.

Efficacy and safety of oral low-dose glucocorticoids in patients with estrogen-dependent primary osteoarthritis.

Estrogen-dependent osteoarthritis (EDPOA) is a disease of perimenopausal-age women. Their manifestations are polyarticular pain with common co-morbidities (carpal tunnel syndrome, insomnia, fatigue, depression, and fibromyalgia). Based on dual role of glucocorticoids, its trophic action on the chondrocyte and its anti-inflammatory effect, we conducted a prospective interventional cohort study where we evaluate the efficacy and safety of oral low-dose GC in one hundred women with EDPOA. The pain intensity, number of tender joints as well as impact in co-morbidities were analyzed. We conclude that the use of low-dose GC in patients with EDPOA can be an effective and a safe therapeutic option.

Efficacy and safety of anti-interleukin 6 receptor monoclonal antibody (tocilizumab) in Colombian patients with Takayasu arteritis.

PURPOSE: The aim of this study was to describe the efficacy and safety of anti-interleukin 6 receptor antibody (tocilizumab [TCZ]) in patients with severe or refractory Takayasu arteritis (TA). METHODS: We describe 8 Colombian patients with severe and/or refractory TA treated with TCZ during a period of at least 9 months. Clinical, radiological, biological, and associated treatments were evaluated before, during, and after TCZ infusions. RESULTS: The median age at evaluation was 31 years (12-43 years). All patients were female and experienced clinical and biological improvement, in addition to a corticosteroid-sparing effect from a median dose of 50 mg/d at baseline (30-60 mg/d) to 6.25 mg/d (2.5-10 mg/d) at 9 months. In 4 cases, in which imaging studies were available, an improvement was observed. The median duration of TCZ infusions was 18 months (9-36 months). Major adverse effects related to TCZ were not evidenced during a period of at least 9 months of treatment. One relapse was observed. Tocilizumab was continued in all cases until the last follow-up. CONCLUSIONS: This study shows a clinical, biological, and radiological response in patients with refractory TA treated with TCZ.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA), medical treatment of severe systemic compromise: case report.

Case description: A 42-year-old woman with severe pulmonary and mediastinal inflammatory involvement, secondary to infiltration of a silicone-related allogenic material with systemic migration. Clinical findings: The patient developed esophageal and bronchial stenosis, recurrent infections, malnutrition, and respiratory deterioration, making surgical removal of the allogenic material impossible. Treatment and outcome: Clinical and radiological improvement was achieved after treatment with multiple intravenous and oral immunomodulators. Clinical relevance: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a heterogeneous disease resulting from exposure to allogenic substances in a susceptible subject. These substances cause autoimmune or autoinflammatory phenomena. Since ASIA was described ten years ago, its diagnostic criteria are still under discussion, with an uncertain prognosis. The ideal therapy is based on eliminating the causative substance, but this is not always possible. Therefore, it is necessary to start an immunomodulatory treatment, using it in this patient, a scheme that had not been previously reported in the literature.

Descripción del caso: Mujer de 42 años con compromiso inflamatorio pulmonar y mediastinal severo, secundario a infiltración de un material alogénico relacionado con la silicona con migración sistémica. Hallazgos clínicos: La paciente desarrolló estenosis esofágica y bronquial, infecciones recurrentes, desnutrición y deterioro respiratorio, imposibilitando la extracción quirúrgica del material alogénico. Tratamiento y resultado: Mejoría clínica y radiológica lograda tras un tratamiento con múltiples inmunomoduladores intravenosos y orales. Relevancia clínica: El síndrome autoinmune / inflamatorio inducido por adyuvantes (ASIA) es una enfermedad heterogénea que resulta de la exposición a sustancias alógenas en un sujeto con susceptibilidad genética. Estas sustancias inducen fenómenos autoinmunitarios o autoinflamatorios. Desde que ASIA fue descrito hace 10 años, sus criterios diagnósticos continúan en discusión, con un pronóstico incierto. El tratamiento idóneo se basa en eliminar la sustancia causante, pero no siempre es posible, por lo cual se hace necesario iniciar un tratamiento inmunomodulador, empleándose en esta paciente un esquema que no había sido reportado previamente en la literatura.

Lymphoid follicular hyperplasia in patients with systemic lupus erythematosus after multiple cycles of rituximab.

Rituximab is indicated in some patients with refractory systemic lupus erythematosus (SLE). Occasionally, this medication is required in chronic form to maintain control of the disease. We described two patients who developed lymphoid follicular hyperplasia (LFH) after multiple cycles of rituximab and evaluated the expression of B cell activating factor belonging to the tumor necrosis factor (TNF) family (BAFF) and its receptors [BAFF-receptor (BAFF-R) and B cell maturation antigen (BCMA)], as possible factors related to lymphoid node enlargement. Two patients with SLE completed six and nine cycles of rituximab (1 g every 2 weeks) indicated each 9 months, achieving remission for 5 and 7 years, respectively, when developed prominent lymphadenopathies. Biopsies showed LFH. Haematological neoplasms were ruled out. Immunohistochemistry showed BAFF overexpression in the follicles, and moderate expression of BAFF-R confined to the mantle zone and BCMA to the germinal centre. Belimumab B cell activating factor belonging to the TNF family (anti-BAFF therapy) was started with positive effects on the clinical condition. LFH can develop in patients with SLE who received multiple cycles of rituximab. BAFF overexpression and moderate expression of BAFF-R and BCMA in lymph nodes were seen. These findings added to the improvement with the change to belimumab could suggest that LFH after cluster of differentiation (CD20) depletion therapy may be associated with a compensatory overexpression of BAFF and its receptors.

Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It.

COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.

Autoantibodies production and immunological abnormalities after bariatric surgery.

OBJECTIVE: Bariatric surgery is a widely used procedure for the treatment of obesity. Our aim is to describe the main immunological changes in patients who undergo bariatric surgery. METHODS: A prospective study was conducted within a cohort of patients undergoing bariatric surgery and without previous evidence of systemic or organ-specific autoimmune diseases in whom 3 blood samples were collected - one day before surgery (Time 0), and 5 (Time 1) and 10 months (Time 2) after surgery. RESULTS: Thirty four obese patients underwent surgery (Time 0):30(88.24%) were women, mean age 38.3 years. When comparing Time 0 and Time 2, there were statistically significant changes in CD4+T cell count, with an increase from 1074/mL(IQR:860-1316) to 1217.5/mL(IQR:838-1510),p = 0.0002. The CD4/CD8 ratio increased from 2.2(IQR: 1.7-2.7) to 2.4(1.8-2.8), p = 0.0001. As for humoral variables, the C3 fraction of complement decreased from 164 ±â€¯40.6 mg/dL to 112.4 ±â€¯31.4 mg/dL(p < 0.001) and C4 decreased from 29.3 ±â€¯10.1 mg/dL to 22.5 ±â€¯7.1(p = 0.0009) at Time 2. Four patients with negative ANAs at baseline, showed positive ANAs at Time 2.One patient developed anti-citrullinated peptide antibodies >200 IU/mL at Time 2. CONCLUSIONS: Patients undergoing bariatric surgery show immunological changes which might eventually lead to develop an autoimmune disease.

Successful Treatment for Severe Thyroid-associated Ophthalmopathy with Tocilizumab.

BACKGROUND AND OBJECTIVE: Thyroid-associated ophthalmopathy (TAO) is the most common extrathyroidal manifestation of Graves disease, occasionally severe and refractory to treatment, mainly in long-term disease. In these cases, one of the most important infiltrating cytokines in the orbital tissue is interleukin-6 (IL-6). METHODS: This is a case report, the methodology consisted of the application of tocilizumab in a patient with graves disease and the patient's follow-up. RESULTS: We present the case of a 54-year-old male with TAO who responded adequately to treatment with tocilizumab, an antibody directed against the IL-6 receptor. CONCLUSION: Tocilizumab could be an optional treatment in patients with TAO.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA), medical treatment of severe systemic compromise: case report

Case description: A 42-year-old woman with severe pulmonary and mediastinal inflammatory involvement, secondary to infiltration of a silicone-related allogenic material with systemic migration. Clinical findings: The patient developed esophageal and bronchial stenosis, recurrent infections, malnutrition, and respiratory deterioration, making surgical removal of the allogenic material impossible. Treatment and outcome: Clinical and radiological improvement was achieved after treatment with multiple intravenous and oral immunomodulators. Clinical relevance: Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) is a heterogeneous disease resulting from exposure to allogenic substances in a susceptible subject. These substances cause autoimmune or autoinflammatory phenomena. Since ASIA was described ten years ago, its diagnostic criteria are still under discussion, with an uncertain prognosis. The ideal therapy is based on eliminating the causative substance, but this is not always possible. Therefore, it is necessary to start an immunomodulatory treatment, using it in this patient, a scheme that had not been previously reported in the literature.

Descripción del caso: Mujer de 42 años con compromiso inflamatorio pulmonar y mediastinal severo, secundario a infiltración de un material alogénico relacionado con la silicona con migración sistémica. Hallazgos clínicos: La paciente desarrolló estenosis esofágica y bronquial, infecciones recurrentes, desnutrición y deterioro respiratorio, imposibilitando la extracción quirúrgica del material alogénico. Tratamiento y resultado: Mejoría clínica y radiológica lograda tras un tratamiento con múltiples inmunomoduladores intravenosos y orales. Relevancia clínica: El síndrome autoinmune / inflamatorio inducido por adyuvantes (ASIA) es una enfermedad heterogénea que resulta de la exposición a sustancias alógenas en un sujeto con susceptibilidad genética. Estas sustancias inducen fenómenos autoinmunitarios o autoinflamatorios. Desde que ASIA fue descrito hace 10 años, sus criterios diagnósticos continúan en discusión, con un pronóstico incierto. El tratamiento idóneo se basa en eliminar la sustancia causante, pero no siempre es posible, por lo cual se hace necesario iniciar un tratamiento inmunomodulador, empleándose en esta paciente un esquema que no había sido reportado previamente en la literatura.

Sequential rituximab and omalizumab for the treatment of eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome).

Eosinophilic granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome (CSS), is a small vessel vasculitis associated with eosinophilia and asthma. Clinical manifestations commonly seen in patients presenting with EGPA range from upper airway and lung involvement to neurological, cardiac, cutaneous, and renal manifestations. Treatment for severe presentations includes steroids, cyclophosphamide, plasmapheresis, and recently, rituximab. Rituximab is associated with a good response in the treatment of vasculitis, but a variable response for the control of allergic symptoms. Here, we report a 16-year-old female patient with severe EGPA (gastrointestinal and cutaneous vasculitis, rhinitis and asthma) refractory to conventional treatment. She was treated with rituximab, which enabled rapid control of the vasculitis component of the disease, but there was no response to rhinitis and asthma. Additionally, she developed severe bronchospasm during rituximab infusion. Sequential rituximab and omalizumab were initiated, leading to remission of all manifestations of vasculitis, rhinitis, and asthma, in addition to bronchospasm related to rituximab infusion.

Epigenetics changes associated to environmental triggers in autoimmunity.

Autoimmune diseases (AIDs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens and represent a heterogeneous group of disorders that affect specific target organs or multiple organs in different systems. While the pathogenesis of AID remains unclear, its aetiology is multifunctional and includes a combination of genetic, epigenetic, immunological and environmental factors. In AIDs, several epigenetic mechanisms are defective including DNA demethylation, abnormal chromatin positioning associated with autoantibody production and abnormalities in the expression of RNA interference (RNAi). It is known that environmental factors may interfere with DNA methylation and histone modifications, however, little is known about epigenetic changes derived of regulation of RNAi. An approach to the known environmental factors and the mechanisms that alter the epigenetic regulation in AIDs (with emphasis in systemic lupus erythematosus, the prototype of systemic AID) are showed in this review.

Etanercept-induced pityriasis lichenoides chronica in a patient with rheumatoid arthritis.

We present a 74-year-old female patient who developed a pityriasis lichenoides chronica (PLC) during etanercept therapy. This association is not described in the literature and might be considered in the spectrum of cutaneous adverse reactions of etanercept.

Pneumocystis jirovecii Pneumonia in a Patient with Rheumatoid Arthritis Treated with Abatacept.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial membrane inflammation and joint cartilage destruction. Abatacept is a biologic agent that blocks the costimulation signals, preventing antigen presentation and proliferation of T lymphocytes. It is approved for the treatment of patients with RA. Pneumocystis jirovecii pneumonia (PJP) is an infectious disease complicating several immunosuppressive drugs. PJP associated with abatacept has not been reported yet in the medical literature. Various factors, such as the mechanism of action of abatacept, may contribute to predisposing to Pneumocystis jirovecii infection. In this paper, we report a patient with RA who developed PJP under abatacept treatment.

Calcium, channels, intracellular signaling and autoimmunity.

Calcium (Ca²âº) is an important cation able to function as a second messenger in different cells of the immune system, particularly in B and T lymphocytes, macrophages and mastocytes, among others. Recent discoveries related to the entry of Ca²âº through the store-operated calcium entry (SOCE) has opened a new investigation area about the cell destiny regulated by Ca²âº especially in B and T lymphocytes. SOCE acts through calcium-release-activated calcium (CRAC) channels. The function of CRAC depends of two recently discovered regulators: the Ca²âº sensor in the endoplasmic reticulum or stromal interaction molecule (STIM-1) and one subunit of CRAC channels called Orai1. This review focuses on the role of Ca²âº signals in B and T lymphocytes functions, the signalling pathways leading to Ca²âº influx, and the relationship between Ca²âº signals and autoimmune diseases.