New Onset Autoimmune Diseases after the Sputnik Vaccine.

The vertiginous advance for identifying the genomic sequence of SARS-CoV-2 allowed the development of a vaccine including mRNA-based vaccines, inactivated viruses, protein subunits, and adenoviral vaccines such as Sputnik. This study aims to report on autoimmune disease manifestations that occurred following COVID-19 Sputnik vaccination. Patients and Methods: A retrospective study was conducted on patients with new-onset autoimmune diseases induced by a post-COVID-19 vaccine between March 2021 and December 2022, in two referral hospitals in Mexico City and Argentina. The study evaluated patients who received the Sputnik vaccine and developed recent-onset autoimmune diseases. Results: Twenty-eight patients developed recent-onset autoimmune diseases after Sputnik vaccine. The median age was 56.9 ± 21.7 years, with 14 females and 14 males. The autoimmune diseases observed were neurological in 13 patients (46%), hematological autoimmune manifestations occurred in 12 patients (42%), with thrombotic disease observed in 10 patients (28%), and autoimmune hemolytic anemia in two patients (7.1%). Rheumatological disorders were present in two patients (7.1%), and endocrine disorders in one patient (3.5%). Principio del formulario Conclusion: Although the COVID-19 Sputnik vaccine is generally safe, it can lead to adverse effects. Thrombosis and Guillain-Barre were the most frequent manifestations observed in our group of patients.

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) in 2023.

In 2011, a syndrome entitled ASIA (Autoimmune/inflammatory Syndrome Induced by Adjuvants; Shoenfeld's syndrome) was first described. ASIA aimed to organize under a single umbrella, the existing evidence regarding certain environmental factors which possess immune stimulatory properties, in order to shed light on a common pathway of autoimmune pathogenesis. Such environmental immune stimulators, or adjuvants, include among others: aluminum salts as in vaccines, various medical implants, as well as various infectious agents. After the launch of the ASIA syndrome, the expansion and recognition of this syndrome by different researchers from different countries began. During the past decades, evidence had been accumulating that (auto)immune symptoms can be triggered by exposure to environmental immune stimulatory factors that act as an adjuvant in genetically susceptible individuals. A panoply of unexplained subjective and autonomic-related symptoms has been reported in patients with ASIA syndrome. The current review summarizes and updates accumulated knowledge from the past decades, describing new adjuvants- (e.g. polypropylene meshes) and vaccine- (e.g. HPV and COVID vaccines) induced ASIA. Furthermore, a direct association between inflammatory/autoimmune diseases with ASIA syndrome, will be discussed. Recent cases will strengthen some of the criteria depicted in ASIA syndrome such as clear improvement of symptoms by the removal of adjuvants (e.g. silicone breast implants) from the body of patients. Finally, we will introduce additional factors to be included in the criteria for ASIA syndrome such as: (1) dysregulated non-classical autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system and (2)) small fiber neuropathy (SFN), both of which might explain, at least in part, the development of 'dysautonomia' reported in many ASIA patients.

Autoimmune/inflammatory syndrome induced by methylmethacrylate associated to seronegative antiphospholipid syndrome and diffuse large B-cell non-Hodgkin's lymphoma.

BACKGROUND: Autoimmune/inflammatory syndrome induced by adjuvants has been associated with different substances used for cosmetic purposes; for example, silicone, methylmethacrylate, autoimmune disorders and cancer. DISCUSSION: A 40-year-old man with a prior history of methylmethacrylate injection in the buttocks for aesthetic purposes 8 years ago, presented with deep venous thrombosis in the left leg 6 months ago, accompanied with inflammation, hardening, changes in colour, ulceration in the buttocks, arthritis, myalgias and fever. Weak and moderate lupus anticoagulant and low levels of anticardiolipin antibodies were present. Thoracoabdominal tomography showed hepatosplenomegaly and a pulmonary nodule, the biopsy of which showed chronic granulomatous inflammation. After a month, a new chest tomography showed multiple nodular pulmonary lesions. The new pulmonary biopsy showed a diffuse large B-cell non-Hodgkin's lymphoma which was treated with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab for four cycles, with good response of the autoimmune/inflammatory syndrome, but partial response of the diffuse large B-cell non-Hodgkin's lymphoma. CONCLUSION: We describe the first case of seronegative antiphospholipid syndrome and lymphoma associated with methylmethacrylate in a patient with autoimmune/inflammatory syndrome.

Primary antiphospholipid syndrome, Addison disease, and adrenal incidentaloma.

Primary adrenal failure comprises an insufficient production of mineralocorticoids and glucocorticoids in the adrenal cortex. A rare manifestation of antiphospholipid syndrome (APS) is adrenal failure. The majority of patients with adrenal involvement in APS develop an irreversible cortisol deficiency and atrophy of the adrenal glands. Adrenal incidentalomas are adrenal masses larger than 1 cm that are discovered in the course of diagnostic evaluation or treatment for another medical condition. Its prevalence is calculated in 1.5-9% of individuals. We describe an exceptional case of a 23-year-old male patient with APS with persistent high levels of antiphospholipid antibodies (aPL) from the time of diagnosis, who developed Addison's disease as a manifestation of APS with atrophy of the adrenal glands, in whom an adrenal incidentaloma was developed later and was corroborated as an aldosterone-producing adenoma. Currently, the patient is asymptomatic and without manifestations of tumor recurrence. The protumoral effect of elevated and persistent aPL is discussed.

Early Detection of Vascular Obstruction in Microvascular Flaps Using a Thermographic Camera.

BACKGROUND: In microsurgical reconstruction, vascular obstruction occurs in approximately 20% of patients. Close monitoring is central to their care. Clinical/Doppler detection of vascular obstruction could be enhanced by thermography. METHODS: A diagnostic test design included consecutive cases of hospitalized patients, ≥18 years old, who underwent surgery with free flaps. Two researchers separately evaluated patients with clinical/Doppler methods and thermographic camera hourly for 24 hours, every 2 hours for the next 24 hours, and then every 3 hours until discharge. The gold standard was visualization of thrombus or vascular obstruction during surgical reintervention. Sensitivity, specificity, positive/negative predictive value (PPV/NPV), and a delta temperature receiver operating characteristic (ROC) curve were calculated. RESULTS: A total of 2,364 tests were performed with a thermographic camera in 40 patients (31 females, 9 males) aged 50.12 ± 9.7 years. There were 28 deep inferior epigastric perforator, 5 anterolateral thigh, 3 radial, 2 scapular, 1 fibular, and 1 anteromedial thigh flaps included. Six (15%) had postoperative vascular obstruction (5 venous and 1 arterial). One flap developed partial necrosis and one total necrosis (overall survival 97.5%). ROC curve (area 0.97) showed the best results at ≥ 1.8°C of difference to the surrounding skin. Considering two consecutive positive evaluations, the sensitivity was 93%, specificity 96%, PPV 57%, and NPV 99%. The thermal imaging camera allows to identify the obstruction between 2 and 12 hours before the clinical method. CONCLUSION: Utilizing a thermographic camera can reduce detection time of vascular obstruction by several hours in microvascular free flaps that include the cutaneous island. This method proves useful for early diagnosis of postoperative vascular obstruction.

Autoimmune/inflammatory syndrome induced by mineral oil: a health problem.

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: siliconosis, Gulf War syndrome, macrophagic myofasciitis syndrome, and post-vaccination phenomena. Afterward, other syndromes have been recognized, such as in ASIA by mineral oil (ASIA-MO). These conditions are triggered by adjuvants and they are the result of the interplay of genetic and environmental factors. ASIA-MO is defined as the infiltration of oily type modeling substances for cosmetic purposes. It has been reported in many countries and used surreptitiously. Pathogenesis of ASIA-MO is not clear, but is characterized by chronic granulomatous inflammation, like the pristane model in mice, with increase of proinflammatory cytokines: type I interferons (IFNα and IFNß), systemic lupus erythematosus (SLE), and erosive arthritis. In humans, an increase of interleukin 1 (IL-1) has been found. Clinical spectrum of ASIA-MO is heterogeneous, varying from mild to severe and being local and systemic. The systemic manifestations can be non-specific and specific, meeting criteria for any autoimmune disease (AID), i.e., SLE, rheumatoid arthritis, and systemic sclerosis, among others. The areas of the body where the mineral oil is mostly applied include the following: buttocks (38-72%), breasts (12-16%), lower extremities (18-22%), and face (6-10%). The penis augmentation is also common. Treatment is focused on local and systemic manifestations and requires medical and surgical management representing a challenge for the physician.

Splenectomy in systemic lupus erythematosus and autoimmune hematologic disease: a comparative analysis.

The objective of the study is to analyze the efficacy and safety of splenectomy in the management of refractory autoimmune thrombocytopenia (AT)/autoimmune hemolytic anemia (AIHA) associated or not with systemic lupus erythematosus. Thirty-four patients after splenectomy due to severe AT and/or AIHA were divided into group 1 (G1) 18 SLE/APS patients: 9 AT/SLE patients, 6 SLE/antiphospholipid syndrome (APS), and 3 primary APS. Group 2 (G2): 16 patients without SLE/APS: 2 Fisher-Evans syndrome and 14 AIHA. Surgery approach when (1) platelets ≤ 50,000/ml despite 2 weeks on medical therapy, (2) medically dependent, and (3) medically intolerant or after two hemolytic crises in AIHA patients. Splenectomy response: (1) complete (CR): ≥ 150,000 platelets/ml, (2) partial: 50,000-149,000/ml, or (3) none: ≤ 50,000/ml. CR for AIHA: hemoglobin ≥9 g/dl. STATISTICAL ANALYSIS: descriptive statistics and chi-square test. The mean age was 34.6 years; mean follow-up: 28.5 months. Open splenectomy in 15/34 vs laparoscopy in 19/34 (p = NS). CR in 15/34, G1: 4/18, G2: 11/16, (p = 0.006). Complications in 6/34, 5 from G2 vs 1 from G1 (p = 0.05). Relapse in 7/18 patients in G1 and 3/16 in G2 (p = 0.05). Open and laparoscopic splenectomies in SLE and AT patients are as effective as in those without SLE; however, patients with SLE and APS had more relapses.

Malnutrition is an independent risk factor for mortality in Mexican patients with systemic sclerosis: a cohort study.

Factors for mortality in systemic sclerosis (SSc) vary in different cohorts around the world. Case-control study nested in a cohort. We included patients ≥16 years of age with SSc (ACR/EULAR 2013), from 2005 to 2015. Demographic and clinical variables and causes of mortality were recorded. We calculated Crude Mortality Rate (CMR), Standardized Mortality Ratio (SMR), and Kaplan-Meier survival analysis was performed. A Cox proportional hazard (HR) regression analysis of the potential risk factors associated with mortality was also performed. A total of 220 patients with SSc were included. During follow-up, 28 deaths occurred. The sum of total time contributed by all subjects was 1074 years-person, the CMR was 12.72%, the overall SMR was 4.5, in women 3.7, and in men 4.7. The survival rate at 5 and 10 years was 83 and 70%, respectively. The causes of death were definitively attributed to SSc in 21.4% of the cases, probably in 28.7%, unrelated in 35.6%, and unknown in 14.3%. The direct cause of death of the patients was infection in 25% of cases, cardiovascular disease in 14%, lung involvement in 14%, pulmonary embolism in 11%, and neoplasia in 11%. The Cox regression analysis showed that the factors associated with mortality were: male gender (HR 5.84, CI 95% 1.31-26, p = 0.013), severe Medsger's score for general symptoms (HR 5.12, CI 95% 1.74-14.97, p = 0.021) and severe malnutrition (HR 3.77, CI 95% 1.23-11.06, p = 0.008). Infections, cardiovascular disease, and lung involvement were the leading cause of death. Male gender and severe general affection and malnutrition were associated with a poorer prognosis of SSc.

Severe manifestations of autoimmune syndrome induced by adjuvants (Shoenfeld's syndrome).

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompassing conditions linked to previous exposure to an adjuvant substance. The clinical picture is very heterogeneous, from mild to severe manifestations, including death. However, the systematic analysis of severe ASIA cases has not been performed. The aim of this study was to systematically review the literature on severe ASIA cases. A systematic review of the literature was performed investigating severe ASIA cases. All publications were identified through PubMed, EMBASE, MEDLINE and Cochrane. Articles published from 2011 to 2016 were included. Severe ASIA was arbitrarily defined as follows: major organ involvement, life-threatening conditions, intensive treatment, disability, hospitalization and outcome (survival and death). Cases described before 2011 were excluded. From 2011 to 2016, we identified 4479 ASIA cases, of them 305 fulfilled arbitrary criteria of severe ASIA including our case presentation and 11 deaths. The majority of severe ASIA cases were related to HPV vaccine, silicone, influenza vaccine and mineral oil injections. The interval from exposition to severe manifestation was from 2 days to 23 years. (1) This is the first study that analyzes all cases published on ASIA with severe manifestations. (2) The current HPV vaccine is both effective and generally safe. However, it should be noted that severe autoimmune side effects have been reported in several studies. Severe ASIA may be observed after influenza vaccines, and other vaccines. (3) Efforts should be made to discover the connection between adjuvants, autoimmunity and autoimmune diseases, because there is an increase in cases severe and life-threatening of ASIA.

Clinical, biochemical, and radiological characterization of the calcinosis in a cohort of Mexican patients with systemic sclerosis.

Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually located in extremities but may occur across the board. The aim of our study was to identify and quantify the distribution of calcinosis in a cohort of Mexican patients with SSc and its association with clinical features and autoantibodies. A cohort of patients with SSc (2013 ACR/EULAR criteria), classified in diffuse cutaneous (dcSSc) and limited cutaneous (lcSSc) (Le Roy criteria), was studied. For their analysis, patients were allocated into those with and without calcinosis (clinical and/or radiological). The evaluation included the modified Rodnan scale for skin and Medsger disease severity scale (DSS). Calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) and antinuclear antibodies and extractable nuclear antigens were determined in serum. A total of 109 patients were included, 41 (37 %) with and 68 (63 %) without calcinosis. Calcinosis was more frequent in patients with dcSSc (55 vs 27 %). In total, we identified 354 sites with calcinosis and mean per patient of 12.0 ± 9.1; the most common sites affected were the hands (83 %), proximal upper extremity (27 %), and proximal lower extremity (22 %). Patients with calcinosis had a higher score of Rodnan scale, Mesdger DSS, and frequency of anti-nucleolar and anti-Scl-70 antibodies compared to those without calcinosis. Abnormal PTH elevation was found in 35 % of patients with calcinosis and 23 % without it. The prevalence of calcinosis is high in Mexican patients with SSc, especially in diffuse variety, and is associated with increased severity of disease.

Expression of NLRP3 inflammasome, cytokines and vascular mediators in the skin of systemic sclerosis patients.

BACKGROUND: The activated NLRP3 inflammasome is associated with the etiology of fibrotic diseases. The role of inflammasomes in SSc is still poorly understood. OBJECTIVES: To determine the expression of NLRP3 (nucleotide-binding domain, leucine-rich-repeat-containing family, pyrin domain-containing 3) in the skin of patients with systemic sclerosis (SSc) and its relationship with pro-inflammatory cytokines and vascular mediators expression. METHODS: Skin biopsies were taken from 42 patients with either limited or diffuse SSc (21 lcSSc and 21 dcSSc), and from 13 healthy individuals. Using real-time polymerase chain reaction (PCR), the relative expression of caspase-1, IL-1ß, IL-18, IL-33, TGF-ß, ET-1, iNOS and eNOS genes, were measured. The location of NLRP3 and IL-1ß were also determined by immunohistochemistry. Clinical characteristics were evaluated. RESULTS: The mean age of the patients was 49.3 ± 12.9 (lcSSc), 44.6 ± 1 3.8 (dcSSc), and 45 ± 14.1 (healthy individuals). Compared to healthy individuals, the skin of both subtypes of SSc showed a significant increase (P < 0.05) in NLRP3, caspase-1, IL-1ß, IL-18 and ET-1. Samples of lcSSc also showed a significant increase of eNOS (P < 0.029), iNOS (P < 0.04) and TGF-ß (P < 0.05). Dermal fibrosis evaluated by modified Rodnan skin score (MRSS) had significant correlation with NLRP3, IL-1ß, IL-18, and ET-1. Immunohistochemical analysis showed stronger staining of NLRP3 and IL-1ß cytoplasmic expression in the keratinizing squamous epithelium of skin from SSc patients compared to controls. CONCLUSIONS: This study identified NLRP3 over-expression in skin of patients with SSc. Skin thickness correlates positively with the NLRP3 inflammasome gene expression and with the vascular mediator and pro-fibrotic ET-1, suggesting that NLRP3 inflammasome plays a role in the pathophysiology of skin fibrosis in human SSc.

Primary and secondary central nervous system vasculitis: clinical manifestations, laboratory findings, neuroimaging, and treatment analysis.

The objectives of this study are to compare the initial clinical, laboratory, and imaging features in primary central nervous system vasculitis (PCNSV) vs secondary central nervous system vasculitis (SCNSV) and follow up after treatment with intravenous cyclophosphamide (IV-CYC) plus glucocorticosteroids (GCS): methylprednisolone (MP). Neurological, laboratory, and neuroimaging findings were analyzed in PCNSV and SCNSV patients. Cerebral biopsy (CB) was performed in nine patients. Both groups received at onset MP plus IV-CYC for 6 months, followed by bimonthly IV-CYC plus prednisone (PND) for 12 months. All patients were followed during 36 months. Thirty patients were included (12 PCNSV and 18 SCNSV). Focal and non-focal neurological manifestations were similar in both groups, headache being the most frequent manifestation in both groups. Fatigue, myalgias, arthralgias, neuropathy, low leukocytes and platelets, elevated erythrocyte sedimentation rate, positive antinuclear antibodies (ANA), anti-double-stranded DNA (dsDNA), antineutrophil cytoplasmic antibodies (ANCA), low complement, and rheumatoid factor were more frequent in SCNSV (p < 0.05). In cerebrospinal fluid, pleocytosis and proteins were higher in PCNSV (p < 0.05). Periventricular and subcortical hyperintense lesions were observed in cranial magnetic resonance imaging in both vasculitides. Cerebral angiography and angioresonance showed narrowing of vasculature in all patients in both groups. CB showed gliosis and lymphocytic infiltration within and around the walls in four patients and granulomatous infiltration in the other patients. After treatment, the Kaplan-Meier survival curve showed a higher relapse-free survival in PCNSV (p < 0.05). Neurological manifestations and neuroimaging findings were similar in both groups of vasculitides, but general symptoms, joint, musculoskeletal, and peripheral neuropathy were preponderant in SCNSV. After treatment with IV-CYC and GCS, patients with PCNSV had a higher relapse-free survival than those with SCNSV.

Autoimmunity in connection with a metal implant: a case of autoimmune/autoinflammatory syndrome induced by adjuvants.

Autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) has been recently proposed by Shoenfeld and Agmon-Levin as a new entity that comprises several conditions: the macrophagic-myofasciitis syndrome, the Gulf War syndrome, silicosis and post-vaccination phenomena, autoimmunity related to infectious fragments, hormones, aluminum, silicone, squalene oil, and pristane. We report the case of a 23-year-old woman who developed serial episodes of high fever, extreme fatigue, transient thrombocytopenia, multiple cervical adenopathies, hepatosplenomegaly, anemia, neutropenia, severe proteinuria and urine sediment abnormalities, elevated serum ferritin levels, and transient low positive antinuclear antibodies 1 year after she had a nickel-titanium chin implant for cosmetic reasons. The clinical picture simulated a variety of probable diseases: systemic lupus erythematosus, Kikuchi-Fujimoto syndrome, adult onset Still's disease, antiphospholipid syndrome, and hemophagocytic syndrome, among others, so she underwent an extensive medical investigation including two lymph node biopsies. She received treatment accordingly with steroids, methotrexate, and mofetil mycophenolate, with initial improvement of her symptoms, which recurred every time the dose was reduced. Two and a half years later the patient decided to retire the chin implant and afterwards all her systemic symptoms have disappeared. She remains in good health, without recurrence of any symptom and off medications until today. Albeit this patient fulfills proposed major ASIA criteria, to our knowledge it would be the first description of systemic features of autoinflammation in connection with a metal implant.

Autoantibodies to transcription intermediary factor TIF1ß associated with dermatomyositis.

INTRODUCTION: Myositis specific autoantibodies are associated with unique clinical subsets and are useful biomarkers in polymyositis/dermatomyositis (PM/DM). A 120 kD protein recognized by certain patients with DM was identified and clinical features of patients with this specificity were characterized. METHODS: The 120 kD protein recognized by a prototype serum was purified and identified by mass spectrometry and immunological methods. Autoantibody to this 120 kD protein was screened in sera from 2,356 patients with various diagnoses from four countries, including 254 PM/DM, by immunoprecipitation of 35S-methionine labeled K562 cell extracts. Clinical information of patients with this specificity was collected. RESULTS: The 120 kD protein, which exactly comigrated with PL-12, was identified as transcription intermediary factor TIF1ß (TRIM28) by mass spectrometry and validated by immunoassays. By immunofluorescence, anti-TIF1ß positivity showed a fine-speckled nuclear staining pattern. Four cases of anti-TIF1ß were identified; all are women, one each in a Japanese, African American, Caucasian, and Mexican individual. Three had a diagnosis of DM and one case was classified as having an undifferentiated connective tissue disease with an elevated CPK but without significant muscle symptoms. This individual also had a history of colon cancer, cervical squamous metaplasia and fibroid tumors of the uterus. Myopathy was mild in all cases and resolved without treatment in one case. The anti-TIF1ß specificity was not found in other conditions. CONCLUSIONS: Anti-TIF1ß is a new DM autoantibody associated with a mild form of myopathy. Whether it has an association with malignancy, as in the case of anti-TIF1γ, or other unique features will need to be evaluated in future studies.

Tolerogenic dendritic cells in autoimmune diseases: crucial players in induction and prevention of autoimmunity.

The immune system has evolved to coordinate responses against numerous invading pathogens and simultaneously remain silent facing self-antigens and those derived from commensal organisms. But, if both processes are not maintained in strict balance, a potential threat can emerge due to the risk of chronic inflammation and/or autoimmunity development. Therefore, there is a negative immune regulation where tolerogenic dendritic cells (tDCs) participate actively. Under steady-state conditions, tDC are notably involved in the elimination of autoreactive T cells at the thymus, and in the control of T cells specific to self and harmless antigens in the periphery. But in the presence of foreign antigens in an inflammatory milieu, dendritic cells (DCs) mature and induce T cells activation and their migration to B cell areas to assist in antibody production. Additionally, there are other factors such as infections, anti tumoral immune responses, trauma-mediated disruption, etc. that may induce alterations in the balance between tolerogenic and immunogenic functions of DCs and instigate the development of autoimmune diseases (ADs). Therefore, in recent years, DCs have emerged as therapeutic targets to control of ADs. Diverse strategies in vitro and/or in animal models of ADs have explored the tolerogenic functions of DCs and demonstrated their feasibility to prevent or control an autoimmune process, but still leaving a void in their application in clinical assays. The purpose of this paper is to give a general overview of the current literature on the significance of tDCs in tolerance maintenance to self and innocuous antigens, the most relevant alterations involved in the pathophysiology of ADs, the cellular and molecular mechanisms involved in their tolerogenic function and the current strategies used to exploit their tolerogenic potential.

IL-10/TGF-beta-treated dendritic cells, pulsed with insulin, specifically reduce the response to insulin of CD4+ effector/memory T cells from type 1 diabetic individuals.

INTRODUCTION: Diabetogenic autoreactive T cells with effector/memory characteristics are described in type 1 diabetes patients (T1D). Alternatively activated dendritic cells (aaDCs) have been regarded as promising tools for clinical application in autoimmune diseases (ADs), although their ability to induce antigen-specific tolerance in T cells derived from ADs has yet to be determined. METHODS: Monocyte-derived dendritic cells (DCs) were produced utilizing GM-CSF and IL-4, and aaDCs by adding IL-10 and TGF-beta (10/TGF-DC) during differentiation. Both cell groups were insulin-loaded, maturated with lipopolysaccharide, and cocultured with autologous effector/memory T cells derived from T1D individuals, in order to evaluate the induction of insulin-specific tolerance. RESULTS AND DISCUSSION: In five of eight T1D patients analyzed in vitro, 10/TGF-DC were able to induce insulin-specific tolerance in effector/memory CD4+ T cells (50.4% +/- 13.2 less proliferation), without affecting the proliferative response to an unrelated antigen (candidin). Tolerance induction was dependent on the current activation state of CD4+ T cells in each patient. 10/TGF-DC-stimulated T cells acquired an IL-2(low)IFN-gamma(low)IL-10(high) cytokine profile, and their hyporesponsiveness could be reverted upon exposure to IL-2. This study shows a perspective about the in vitro ability of monocyte-derived 10/TGF-DC to induce antigen-specific tolerance in effector/memory T cells generated during the course of an autoimmune disease.

Catastrophic antiphospholipid syndrome in a patient with Down syndrome.

We report a patient with Down syndrome, under treatment with carbamazepine, levopromazine and clonazepam. After urinary infection he developed glans necrosis requiring excision of prepuce. Six hours post surgery he presented right-hand ischemia followed by arterial and venous thrombosis of the right thoracic extremity. Later, he progressed to a compartment syndrome and presented ischemia of toes. All the clinical manifestations developed over a week. Anticardiolipin (aCL) antibodies, lupus anticoagulant and perinuclear antineutrophil antibodies were positive. Anticoagulant and immunosuppressive treatment were initiated. Owing to the failure of both treatments, the patient underwent amputation of right hand and a toe. Histopathology revealed recent and old thrombosis of medium- and small-sized vessels without vasculitis. Diagnosis of catastrophic antiphospholipid syndrome (CAPS) was made. At present, the patient continues on oral anticoagulants, IgG aCL remains positive, and no further episodes of thromboses have been observed after 4 years of follow-up. To our knowledge, this is the first case of CAPS in a patient with Down syndrome.

Clinical significance of antiphospholipid syndrome nephropathy (APSN) in patients with systemic lupus erythematosus (SLE).

UNLABELLED: Antiphospholipid syndrome nephropathy (APSN) is now a well recognized vaso-occlusive renal lesion associated with acute thrombosis and chronic arterial and arteriolar lesions, leading to zones of cortical ischemic atrophy. Our objective was to evaluate the prevalence and clinical significance of APSN in patients with Systemic Lupus Erythematosus (SLE). METHODS: Kidney biopsy specimens obtained from 162 patients with lupus glomerulonephritis were retrospectively examined for the presence of APSN. Clinical and laboratory data obtained at the time of kidney biopsy and during a mean follow-up of 7 years were recorded. In cases for which serial kidney biopsy specimens were available, the evolution of APSN was examined. RESULTS: We found APSN in 17 (10.4%) patients with lupus glomerulonephritis (GN), 12 with focal or proliferative lesions. Both activity and chronicity indexes were higher in patients with APSN when compared with lupus nephritis without APSN. Patients with APSN had a higher frequency of hypertension and elevated serum creatinine levels at the time or kidney biopsy, as well as a higher frequency of rapidly progressive GN, nephrotic syndrome and death at the end of the follow-up. Anticardiolipin antibodies were found in 52% of those with APSN and in 27% of those without APSN. Serial kidney biopsy specimens were available from 18 patients. An increase of glomerular sclerosis was found in the second biopsy particularly in those patients with APSN in the first biopsy. CONCLUSIONS: APSN is a risk factor that contributes to an elevated prevalence of hypertension, elevated serum creatinine, nephrotic syndrome and increased glomerular sclerosis. APSN should be included in the classification criteria of APS, and the use of appropriate anticoagulant therapy should be tested.

Prevalencia de hipotiroidismo y anticuerpos antitiroglobulina en pacientes mexicanos con esclerosis sistémica / Systemic sclerosis and hypothyroidism

Objetivo: Investigar la prevalencia de hipotiroidismo y anticuerpos antitiroglobulina (AATg) en pacientes mexicanos con esclerosis sistémica (ES). Material y métodos: Se estudió la función tiroidea en pacientes con ES y controles. Se les determinaron los niveles séricos de triyodotironina, tiroxina, hormona estimulante de la tiroides (TSH) y AATg. Resultados: Fueron 110 pacientes (106 mujeres y 4 hombres), edad promedio de 48.1 ± 28.5 años, versus 80 controles (76 mujeres y 4 hombres), edad promedio 47.5 ± 28.8 años. El hipotiroidismo clínico se encontró en 19% de pacientes con ES y en 1.3% de los controles (p < 0.01). Las medianas respectivamente de triyodotironina en ES y controles fueron: 82 versus 160 ng/dl, p < 0.01; tiroxina 5.4 versus 7 ng/dl, p < 0.01; TSH 8.2 versus 1.1 μUI/ml, p < 0.001. El hipotiroidismo subclínico se observó en 35% de los pacientes con ES y en 0% de los controles. Los valores de TSH en ES y en controles fueron 7.2 versus 1.2 μUI/ml, p < 0.01; triyodotironina 116 versus 160 ng/dl, p ns; tiroxina 7 versus 7 ng/dl, p ns, respectivamente. Los AATg estuvieron presentes en 54% de los pacientes y 2.5% en el grupo control, p < 0.01. Conclusiones: Los pacientes con ES presentan elevada prevalencia de hipotiroidismo, especialmente subclínico, por lo que debe investigarse la función tiroidea para iniciar tratamiento oportuno.

OBJECTIVE: Assess the prevalence of hypothyroidism and anti-thyroglobuline antibodies (AbATg) among Mexican patients with systemic sclerosis (SSc). MATERIAL AND METHODS: Thyroid function was studied in SSs patients and controls. Triiodothyronine, thyroxine, thyroid stimulant hormone (TSH) and AbATg were measured. RESULTS: 110 SSc patients (106 women and 4 men), mean age 48.1 +/- 28.5 yrs versus 80 healthy controls (76 women and 4 men) with mean age 47.5 +/- 28.8 yrs were included. Hypothyroidism was diagnosed in 19% patients compared with 1.3% in the control group. The following results were found; triyodotironina: 82 ng/dl versus 160 ng/dl, p < 0.000; tiroxina: 5.4 ng/dl versus 7ng/dl, p < 0.01; TSH: 8.2 uUl/ mL versus 1.1 +/- 2 uUl/mL, p < 0.000. Subclinical hypothyroidism was observed in 35% patients versus 0% controls, TSH: 7.2 uUl/ml versus 1.2 +/- 1.4 uUl/ml, p < 0. 000; triyodotironina: 116 ng/dl compared with 160 ng/dl, p = ns; tiroxina: 7.0 ng/dl vs. 7.0 ng/dl, p ns; AbATg were positive in patients 54% and 2.5%, p < 0.001 in the control group. CONCLUSIONS: Our study reports a high prevalence of hypothyroidism among SSc Mexican patients, especially of the subclinical type. We need to consider hypothyroidism as a clinical entity often found among SSc patients, and start hormone replacment treatment accordingly.