Gabriela Nicolle Sorto Medina - Academia.edu (original) (raw)

Papers by Gabriela Nicolle Sorto Medina

Autoimmune manifestations of infections

Current opinion in rheumatology, Jan 9, 2018

To provide an update about the interactions between infections and autoimmune diseases (AIDs), fr... more To provide an update about the interactions between infections and autoimmune diseases (AIDs), from the molecular perspective to the clinical spectrum and the differentiation between infection and disease activity. Any kind of infection may modify the innate and adaptive immune response through the following mechanisms: molecular mimicry, superantigens, epitope spreading and B-cell activation. The consequence is the overproduction of antibodies shared with those found in AIDs. Viral infections, especially HIV and hepatitis C virus, can stimulate the production of antiphospholipid antibodies and confer an increased risk to develop antiphospholipid syndrome. The identification of risk factors to develop infections in patients with AIDs is remarkable to prevent them. These factors are the use of steroids and immunosuppressants, the involvement of a major organ (lungs, brain and kidney) and severe activity. Biomarkers to differentiate infection from disease activity are scarce, but the ...

Clinical rheumatology, Jan 4, 2018

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: si... more 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 s...

Reumatologia clinica, Jan 11, 2017

Translation, transculturation and validity of the self-administered questionnaire for functionali... more Translation, transculturation and validity of the self-administered questionnaire for functionality (Systemic Sclerosis Questionnaires [SySQ]) for use in Spanish patients with systemic sclerosis and its relationship to the severity of the disease and to quality of life. We conducted an observational analytical study to perform a cross-cultural validation of the self-administered questionnaire on functionality in scleroderma. The validity of the form and content was evaluated by an expert panel. The method included: a) adaptation into Spanish of the construct for translation and back translation, and transculturation; b) internal consistency with the SySQ (Cronbach's alpha), and c) reproducibility was assessed taking into account all occasions in which the test was performed with Cohen's kappa. Additionally, we calculated the Spearman correlation coefficient with the Medsger severity scale, Health Assessment Questionnaire score and SF-36 score. We included 70 patients with sy...

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

Clinical rheumatology, Jan 16, 2018

The objective of the study is to analyze the efficacy and safety of splenectomy in the management... more 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. 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...

The Israel Medical Association journal : IMAJ, 2017

Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of re... more Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of recurrent pregnancy loss and its accurate diagnosis is a requirement for optimal treatment. Some patients do not fulfill the revised Sapporo classification criteria, the original APS classification criteria, and are considered to be non-criteria Obs-APS. In these patients with non-criteria, there is controversy about their inclusion within the spectrum of APS and eventually their treatment as having Obs-APS. A subset of patients may also have clinical characteristics of Obs-APS even though lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I (aβ2GPI) antibodies are consistently negative. These patients are recognized as seronegative Obs-APS. We reviewed evidence of non-criteria Obs-APS and discuss a case of a woman with a diagnosis of active systemic lupus erythematosus (SLE) and non-criteria Obs-APS with four consecutive pregnancy losses. After an accurate diag...

Prolactin has a pathogenic role in systemic lupus erythematosus

Immunologic Research, 2017

Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituita... more Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.

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

Clinical Rheumatology, 2016

Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually located in extr... more 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.

Immunologic Research, 2016

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

Immunologic Research, 2016

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompassing conditions linked to pr... more 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.

Pregnancy outcomes in women with childhood-onset and adult-onset systemic lupus erythematosus: a comparative study

Rheumatology International, 2016

To compare the maternal and fetal outcomes between childhood-onset and adult-onset systemic lupus... more To compare the maternal and fetal outcomes between childhood-onset and adult-onset systemic lupus erythematosus (SLE), we reviewed the medical records of SLE pregnant women treated from January 2005 to August 2013. For comparison, patients were allocated to one of the two groups, those pregnant patients with SLE onset before 18 years of age (childhood-onset) and ≥18 years (adult-onset). The patients were evaluated at least once in each trimester and postpartum. Relevant maternal and fetal outcomes were extracted, such as lupus flare, preeclampsia/eclampsia, rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. We studied 186 pregnancies (in 180 women), 58 of them had childhood-onset SLE, and the remaining 128 had adult-onset SLE. The rate of maternal and fetal complications was similar in both groups. Multivariate analysis showed that active SLE before pregnancy, primigravida, renal flare, preeclampsia, lupus flare, anticardiolipin antibodies, and low serum complement were associated with an increased risk of poor maternal and fetal outcomes. The diagnosis of childhood-onset had no impact on maternal-fetal outcome. The maternal and fetal outcome in women with childhood-onset SLE is similar to that reported in women with adult-onset SLE. Pregnancy in women with childhood-onset SLE should not be contraindicated if the disease is well controlled.

The Journal of rheumatology, 2003

The role of prolactin (PRL) in the pathogenesis of systemic lupus erythematosus (SLE) is controve... more The role of prolactin (PRL) in the pathogenesis of systemic lupus erythematosus (SLE) is controversial. The effect of conventional treatment (steroids, antimalarials, immunosuppressor drugs) on PRL concentrations is unclear. We investigated correlation of PRL levels with lupus activity in patients at entry and after 6 months of conventional treatment. We studied 43 female patients with active SLE, who were divided in 2 groups; Group 1: 16 patients with minor organ involvement (cutaneous and articular involvement), and Group 2: 27 patients with major organ involvement (glomerulonephritis). Controls were 36 healthy individuals. PRL levels were determined by an immunoradiometric assay at entry and after 6 months of treatment. PRL levels were correlated with SLE Disease Activity Index (SLEDAI) score. Mild hyperprolactinemia (HPRL, 20-40 ng/ml) was found in 30/43 (69.7%) SLE patients. After 6 months of treatment a reduction in PRL levels was found in both groups: Group 1: 24.3 +/- 10.8 t...

The Journal of rheumatology, 2006

Hyperprolactinemia (HPRL) has been identified in more than half of patients with systemic scleros... more Hyperprolactinemia (HPRL) has been identified in more than half of patients with systemic sclerosis (SSc). However, the association with pituitary adenoma and the status of hypothalamic dopaminergic tone using metoclopramide (MTC) test has not been studied. We investigated the prevalence of prolactin (PRL)-secreting pituitary adenoma and evaluated production of PRL by dynamic testing with MTC in SSc. We studied 30 patients with SSc (mean age 38 +/- 10 yrs) and 20 healthy controls (mean age 37 +/- 11 yrs). Serum PRL concentrations were determined by radioimmunoassay in all subjects, and PRL response was measured 30, 60, 90, and 120 min after injection of 10 mg of MTC. Computed tomography (CT) of the sella turcica was performed. The mean basal serum PRL levels before and after stimulation with MTC in SSc patients versus controls were: basal 18.2 +/- 5.4 versus 8.7 +/- 1.6 ng/ml, p = NS; 30 min: 175.0 +/- 5.4 versus 61.0 +/- 42 ng/ml, p < 0.001; 60 min: 160 +/- 64 versus 52 +/- 30 n...

The Israel Medical Association journal : IMAJ, 2013

Current Rheumatology Reports, 2009

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an uncommon immune complex-mediated e... more Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an uncommon immune complex-mediated entity characterized by urticaria with persistent acquired hypocomplementemia. First described in 1973, HUVS is associated with several systemic fi ndings including leukocytoclastic vasculitis, severe angioedema, laryngeal edema, pulmonary involvement, arthritis, arthralgia, glomerulonephritis, and uveitis. These manifestations should be present for at least 6 months. Laboratory fi ndings include low complement levels of classical pathway, namely C1q, C2, C3, and C4. The disease marker is the serum presence of anti-C1q antibodies. Treatment, based on disease severity, involves corticosteroids and other immunosuppressive agents that have demonstrated some success. Patients may have signifi cant morbidity and mortality, most commonly caused by chronic obstructive pulmonary disease and acute laryngeal edema.

Risk factors of systemic lupus erythematosus flares during pregnancy

Immunologic Research, 2014

This review examines the risk factors for the development of systemic lupus erythematosus (SLE) f... more This review examines the risk factors for the development of systemic lupus erythematosus (SLE) flares during pregnancy. In preconception, anti-DNA, hypocomplementemia, previous thrombosis, triple antiphospholipid (aPL) antibody positivity, active lupus nephritis and discontinuation of medications such as hydroxychloroquine and azathioprine are factors associated with pregnancy failure. During pregnancy, SLE flares are associated with aPL antibodies, synergic changes of pregnancy on Th1 and TH2 cytokines, other cytokines and chemokines that interact with hormones such as estrogen and prolactin that amplify the inflammatory effect. From the clinical point of view, SLE activity at pregnancy onset, thrombocytopenia, lupus nephritis, arterial hypertension, aPL syndromes, preeclampsia is associated with lupus flares and fetal complications. In puerperium, the risk factors of flares are similar to pregnancy. Hyperactivity of immune system, autoantibodies, hyperprolactinemia, active lupus nephritis, decrease in TH2 cytokines with increase in TH1 cytokines probably participate in SLE flare. The SLE flares during pregnancy make the difference between an uncomplicated pregnancy and pregnancy with maternal and fetal complications. Therefore, the knowledge of risk factors leads the best treatment strategies to reduce flares and fetal complications in SLE patients.

Chapter 16 Pregnancy, Hormones, and Autoimmune Rheumatic Diseases

Handbook of Systemic Autoimmune Diseases, 2008

Publisher Summary This chapter discusses the pregnancy, hormones, and autoimmune rheumatic diseas... more Publisher Summary This chapter discusses the pregnancy, hormones, and autoimmune rheumatic diseases. It analyzes the influence of the immune–neuroendo-crine system on autoimmune disease during pregnancy. Pregnancy is a physiological condition characterized by complex molecular interactions between the mother and the embryo. Inadequate progesterone secretion, luteal phase deficiency, hyperprolactinemia, thyroid disease, hypopara-thyroidism, uncontrolled diabetes, decreased ovarian reserve, and polycystic ovarian syndrome are some examples of conditions that affect the outcome of pregnancy. Cytokines make important contributions to successful pregnancy. Th1 and Th2 cytokines play roles at different stages of pregnancy. During pregnancy, experimental animals and patients with autoimmune diseases develop abnormal immune–neuroendocrine responses. The placenta plays a key role in the maintenance of local tolerance and allows the mother to accept the embryo until completion of pregnancy. During normal pregnancy, cellular immunity and Th1 cytokines, which are potentially harmful to the fetus, are inhibited, whereas humoral immunity, autoantibody production, and Th2 cytokines are enhanced.

Interaction between Rheumatoid Arthritis and Infections

Infection and Autoimmunity, 2004

Publisher Summary Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characteri... more Publisher Summary Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by a symmetric inflammation and destruction of joints. Despite of large efforts and technology, the etiology of RA remains elusive, although it appears that genetic, infectious, environmental, and hormonal factors are all involved in complex interrelated ways. One of the most exciting areas of investigation is the application of Polymerase Chain Reaction (PCR). This technique is useful to the detection of bacterial and viral DNA in patients with RA. With PCR technique, foreign antigens of bacteria, virus, and superantigens can be found in the synovial fluid. In addition, the lymphocytes from synovial fluid can develop a local immune response stimulated by microorganisms such as Proteus mirabilis and Epstein-Barr virus. These lymphocyte responses were higher with these microorganisms than with other stimuli. Those data suggest an immune-infectious cause for RA. However, the difficulty of separating pathogens from contaminants has hampered these studies. On the other hand, the presence of foreign antigens is not specific for RA. Therefore, the role of these organisms in initiating and perpetuating inflammation in RA remains unknown; however, it continues to be actively investigated. This chapter provides an update on the various mechanisms in which infectious agents may play a role as inciting or perpetuating factors in the pathogenesis of RA.

Clinical spectrum of males with primary antiphospholipid syndrome and systemic lupus erythematosus: a comparative study of 73 patients

Lupus, 2004

The objective of this study was to compare the clinical findings, laboratory data, functional out... more The objective of this study was to compare the clinical findings, laboratory data, functional outcome and chronic damage in male patients with primary antiphospholipid syndrome (PAPS) and systemic lupus erythematosus (SLE). We studied 29 male patients with PAPS and 44 with SLE. Clinical findings, laboratory data, lupus damage index (SLICC/ACR DI), and functional outcome in PAPS, were analysed in each group. The mean age at diagnosiswas 29.8 + 10.4 years in patientswith PAPS and 26 + 10.1 years in SLE patients. The duration of disease was 4.5 + 2.6 versus 5.2 + 3.8 years in patients with PAPS and SLE, respectively(P NS). In patients with PAPS the most frequent clinical manifestations were venous thrombosis, thrombocytopenia, and pulmonary thromboembolism. Patients with SLE had joint, skin and renal involvement more frequently than those with PAPS (P 0.0001). All PAPS patients had anticardiolipin antibodies (aCL), and 14 patients (48%) had lupus anticoagulant (LA). All SLE patients ha...

The impact of gender on clinical manifestations of primary antiphospholipid syndrome

Lupus, 2005

The objective of the study was to determine the clinical differences at diagnosis and during foll... more The objective of the study was to determine the clinical differences at diagnosis and during follow-up between male and female patients with primary antiphospholipid syndrome (PAPS). We analysed 68 patients, 30 males and 38 females diagnosed and followed between 1990 and 2003. Patients with antiphospholipid syndrome associated with systemic lupus erythematosus at onset and during follow-up were excluded. The mean age at diagnosis was 31.4 ± 11 years in males and 35.7 ± 11 years in females (NS). The follow-up after diagnosis was 8.7 ± 3.1 years in males and 9.2 ± 2.9 years in females (NS). We did not find significant differences between the two groups with respect to venous and arterial thrombosis. However, in female patients, stroke was more prevalent than in male patients (12/38 versus 3/30, P = 0.03). In contrast, we found a significant prevalence of severe gastrointestinal complications in male compared to female patients (7/30 versus 1/38, P = 0.009). One male patient died due t...

Endothelial dysfunction in patients with antiphospholipid syndrome assessed with positron emission tomography

Journal of Nuclear Cardiology, 2007

There is limited knowledge about endothelial dysfunction in patients with primary antiphospholipi... more There is limited knowledge about endothelial dysfunction in patients with primary antiphospholipid syndrome (PAPS). The purpose of this study was to evaluate endothelial function in patients with PAPS assessed by positron emission tomography. A 3-phase protocol--rest, cold pressor test (CPT), and adenosine positron emission tomography with nitrogen 13 ammonia--was used in 18 patients with PAPS and 18 healthy volunteers (HVs). Myocardial blood flow (MBF) was measured in each phase, with calculation of the endothelial-dependent vasodilation index, the increase in the MBF in response to CPT, and the myocardial flow reserve. An important trend was found in the myocardial flow reserve (2.76 +/- 1.04 in PAPS group vs 3.27 +/- 0.72 in HV group, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05), in the endothelial-dependent vasodilation index (1.19 +/- 0.31 in PAPS group vs 1.55 +/- 0.37 in HV group, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05), and in the percent change in the MBF in response to CPT (from rest) (19% +/- 31% in PAPS group vs 55% +/- 37% in HV group, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). The CPT results obtained in this study showed that the PAPS patients studied have endothelial dysfunction.

Autoimmune manifestations of infections

Current opinion in rheumatology, Jan 9, 2018

To provide an update about the interactions between infections and autoimmune diseases (AIDs), fr... more To provide an update about the interactions between infections and autoimmune diseases (AIDs), from the molecular perspective to the clinical spectrum and the differentiation between infection and disease activity. Any kind of infection may modify the innate and adaptive immune response through the following mechanisms: molecular mimicry, superantigens, epitope spreading and B-cell activation. The consequence is the overproduction of antibodies shared with those found in AIDs. Viral infections, especially HIV and hepatitis C virus, can stimulate the production of antiphospholipid antibodies and confer an increased risk to develop antiphospholipid syndrome. The identification of risk factors to develop infections in patients with AIDs is remarkable to prevent them. These factors are the use of steroids and immunosuppressants, the involvement of a major organ (lungs, brain and kidney) and severe activity. Biomarkers to differentiate infection from disease activity are scarce, but the ...

Clinical rheumatology, Jan 4, 2018

Autoimmune/inflammatory syndrome induced by adjuvant (ASIA) includes the following conditions: si... more 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 s...

Reumatologia clinica, Jan 11, 2017

Translation, transculturation and validity of the self-administered questionnaire for functionali... more Translation, transculturation and validity of the self-administered questionnaire for functionality (Systemic Sclerosis Questionnaires [SySQ]) for use in Spanish patients with systemic sclerosis and its relationship to the severity of the disease and to quality of life. We conducted an observational analytical study to perform a cross-cultural validation of the self-administered questionnaire on functionality in scleroderma. The validity of the form and content was evaluated by an expert panel. The method included: a) adaptation into Spanish of the construct for translation and back translation, and transculturation; b) internal consistency with the SySQ (Cronbach's alpha), and c) reproducibility was assessed taking into account all occasions in which the test was performed with Cohen's kappa. Additionally, we calculated the Spearman correlation coefficient with the Medsger severity scale, Health Assessment Questionnaire score and SF-36 score. We included 70 patients with sy...

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

Clinical rheumatology, Jan 16, 2018

The objective of the study is to analyze the efficacy and safety of splenectomy in the management... more 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. 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...

The Israel Medical Association journal : IMAJ, 2017

Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of re... more Obstetric antiphospholipid syndrome (Obs-APS) is one of the most commonly identified causes of recurrent pregnancy loss and its accurate diagnosis is a requirement for optimal treatment. Some patients do not fulfill the revised Sapporo classification criteria, the original APS classification criteria, and are considered to be non-criteria Obs-APS. In these patients with non-criteria, there is controversy about their inclusion within the spectrum of APS and eventually their treatment as having Obs-APS. A subset of patients may also have clinical characteristics of Obs-APS even though lupus anticoagulant (LA), anticardiolipin antibodies, and anti-β2-glycoprotein I (aβ2GPI) antibodies are consistently negative. These patients are recognized as seronegative Obs-APS. We reviewed evidence of non-criteria Obs-APS and discuss a case of a woman with a diagnosis of active systemic lupus erythematosus (SLE) and non-criteria Obs-APS with four consecutive pregnancy losses. After an accurate diag...

Prolactin has a pathogenic role in systemic lupus erythematosus

Immunologic Research, 2017

Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituita... more Prolactin, a 23-kDa peptide hormone, is produced by the anterior pituitary gland and extrapituitary sites including the immune cells. Prolactin (PRL) participates in innate and adaptive immune response. PRL stimulates the immune cells by binding to receptor (PRL-R). Binding of PRL to its receptor activates the Janus kinase-signal transducer (JAK-STAT). Activation of these cascades results in endpoints such as immunoestimulator and immunosupressor action. Prolactin belongs to the network of immune-neuroendocrine interaction. Hyperprolactinemia has been found in patients with systemic lupus erythematosus (SLE), and new evidence has confirmed a significant correlation between serum PRL levels and disease activity. PRL participates in activation of SLE during pregnancy and in pathogenesis of lupus nephritis, neuropsychiatric, serosal, hematologic, articular, and cutaneous involvement. Hyperprolactinemia was associated with increase IgG concentrations, anti-DNA antibodies, immune complex, glomerulonephritis, and accelerated mortality in murine lupus. Bromocriptine, a dopamine analog that suppresses PRL secretion, was associated with decreased lupus activity, prolonged lifespan, and restoration of immune competence in experimental model. In clinical trials, bromocriptine and derivative drugs showed beneficial therapeutic effect in treating human lupus, including pregnancy. Taken together, clinical and experimental results leave little doubt that PRL indeed contributes to the pathogenesis and clinical expression of SLE.

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

Clinical Rheumatology, 2016

Calcinosis is a frequent complication of systemic sclerosis (SSc) that is usually located in extr... more 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.

Immunologic Research, 2016

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

Immunologic Research, 2016

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) encompassing conditions linked to pr... more 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.

Pregnancy outcomes in women with childhood-onset and adult-onset systemic lupus erythematosus: a comparative study

Rheumatology International, 2016

To compare the maternal and fetal outcomes between childhood-onset and adult-onset systemic lupus... more To compare the maternal and fetal outcomes between childhood-onset and adult-onset systemic lupus erythematosus (SLE), we reviewed the medical records of SLE pregnant women treated from January 2005 to August 2013. For comparison, patients were allocated to one of the two groups, those pregnant patients with SLE onset before 18 years of age (childhood-onset) and ≥18 years (adult-onset). The patients were evaluated at least once in each trimester and postpartum. Relevant maternal and fetal outcomes were extracted, such as lupus flare, preeclampsia/eclampsia, rate of liveborns, fetal loss (spontaneous abortion and stillbirth), term delivery, preterm birth, neonatal death, low birth weight, low birth weight at term, and congenital malformations. We studied 186 pregnancies (in 180 women), 58 of them had childhood-onset SLE, and the remaining 128 had adult-onset SLE. The rate of maternal and fetal complications was similar in both groups. Multivariate analysis showed that active SLE before pregnancy, primigravida, renal flare, preeclampsia, lupus flare, anticardiolipin antibodies, and low serum complement were associated with an increased risk of poor maternal and fetal outcomes. The diagnosis of childhood-onset had no impact on maternal-fetal outcome. The maternal and fetal outcome in women with childhood-onset SLE is similar to that reported in women with adult-onset SLE. Pregnancy in women with childhood-onset SLE should not be contraindicated if the disease is well controlled.

The Journal of rheumatology, 2003

The role of prolactin (PRL) in the pathogenesis of systemic lupus erythematosus (SLE) is controve... more The role of prolactin (PRL) in the pathogenesis of systemic lupus erythematosus (SLE) is controversial. The effect of conventional treatment (steroids, antimalarials, immunosuppressor drugs) on PRL concentrations is unclear. We investigated correlation of PRL levels with lupus activity in patients at entry and after 6 months of conventional treatment. We studied 43 female patients with active SLE, who were divided in 2 groups; Group 1: 16 patients with minor organ involvement (cutaneous and articular involvement), and Group 2: 27 patients with major organ involvement (glomerulonephritis). Controls were 36 healthy individuals. PRL levels were determined by an immunoradiometric assay at entry and after 6 months of treatment. PRL levels were correlated with SLE Disease Activity Index (SLEDAI) score. Mild hyperprolactinemia (HPRL, 20-40 ng/ml) was found in 30/43 (69.7%) SLE patients. After 6 months of treatment a reduction in PRL levels was found in both groups: Group 1: 24.3 +/- 10.8 t...

The Journal of rheumatology, 2006

Hyperprolactinemia (HPRL) has been identified in more than half of patients with systemic scleros... more Hyperprolactinemia (HPRL) has been identified in more than half of patients with systemic sclerosis (SSc). However, the association with pituitary adenoma and the status of hypothalamic dopaminergic tone using metoclopramide (MTC) test has not been studied. We investigated the prevalence of prolactin (PRL)-secreting pituitary adenoma and evaluated production of PRL by dynamic testing with MTC in SSc. We studied 30 patients with SSc (mean age 38 +/- 10 yrs) and 20 healthy controls (mean age 37 +/- 11 yrs). Serum PRL concentrations were determined by radioimmunoassay in all subjects, and PRL response was measured 30, 60, 90, and 120 min after injection of 10 mg of MTC. Computed tomography (CT) of the sella turcica was performed. The mean basal serum PRL levels before and after stimulation with MTC in SSc patients versus controls were: basal 18.2 +/- 5.4 versus 8.7 +/- 1.6 ng/ml, p = NS; 30 min: 175.0 +/- 5.4 versus 61.0 +/- 42 ng/ml, p < 0.001; 60 min: 160 +/- 64 versus 52 +/- 30 n...

The Israel Medical Association journal : IMAJ, 2013

Current Rheumatology Reports, 2009

Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an uncommon immune complex-mediated e... more Hypocomplementemic urticarial vasculitis syndrome (HUVS) is an uncommon immune complex-mediated entity characterized by urticaria with persistent acquired hypocomplementemia. First described in 1973, HUVS is associated with several systemic fi ndings including leukocytoclastic vasculitis, severe angioedema, laryngeal edema, pulmonary involvement, arthritis, arthralgia, glomerulonephritis, and uveitis. These manifestations should be present for at least 6 months. Laboratory fi ndings include low complement levels of classical pathway, namely C1q, C2, C3, and C4. The disease marker is the serum presence of anti-C1q antibodies. Treatment, based on disease severity, involves corticosteroids and other immunosuppressive agents that have demonstrated some success. Patients may have signifi cant morbidity and mortality, most commonly caused by chronic obstructive pulmonary disease and acute laryngeal edema.

Risk factors of systemic lupus erythematosus flares during pregnancy

Immunologic Research, 2014

This review examines the risk factors for the development of systemic lupus erythematosus (SLE) f... more This review examines the risk factors for the development of systemic lupus erythematosus (SLE) flares during pregnancy. In preconception, anti-DNA, hypocomplementemia, previous thrombosis, triple antiphospholipid (aPL) antibody positivity, active lupus nephritis and discontinuation of medications such as hydroxychloroquine and azathioprine are factors associated with pregnancy failure. During pregnancy, SLE flares are associated with aPL antibodies, synergic changes of pregnancy on Th1 and TH2 cytokines, other cytokines and chemokines that interact with hormones such as estrogen and prolactin that amplify the inflammatory effect. From the clinical point of view, SLE activity at pregnancy onset, thrombocytopenia, lupus nephritis, arterial hypertension, aPL syndromes, preeclampsia is associated with lupus flares and fetal complications. In puerperium, the risk factors of flares are similar to pregnancy. Hyperactivity of immune system, autoantibodies, hyperprolactinemia, active lupus nephritis, decrease in TH2 cytokines with increase in TH1 cytokines probably participate in SLE flare. The SLE flares during pregnancy make the difference between an uncomplicated pregnancy and pregnancy with maternal and fetal complications. Therefore, the knowledge of risk factors leads the best treatment strategies to reduce flares and fetal complications in SLE patients.

Chapter 16 Pregnancy, Hormones, and Autoimmune Rheumatic Diseases

Handbook of Systemic Autoimmune Diseases, 2008

Publisher Summary This chapter discusses the pregnancy, hormones, and autoimmune rheumatic diseas... more Publisher Summary This chapter discusses the pregnancy, hormones, and autoimmune rheumatic diseases. It analyzes the influence of the immune–neuroendo-crine system on autoimmune disease during pregnancy. Pregnancy is a physiological condition characterized by complex molecular interactions between the mother and the embryo. Inadequate progesterone secretion, luteal phase deficiency, hyperprolactinemia, thyroid disease, hypopara-thyroidism, uncontrolled diabetes, decreased ovarian reserve, and polycystic ovarian syndrome are some examples of conditions that affect the outcome of pregnancy. Cytokines make important contributions to successful pregnancy. Th1 and Th2 cytokines play roles at different stages of pregnancy. During pregnancy, experimental animals and patients with autoimmune diseases develop abnormal immune–neuroendocrine responses. The placenta plays a key role in the maintenance of local tolerance and allows the mother to accept the embryo until completion of pregnancy. During normal pregnancy, cellular immunity and Th1 cytokines, which are potentially harmful to the fetus, are inhibited, whereas humoral immunity, autoantibody production, and Th2 cytokines are enhanced.

Interaction between Rheumatoid Arthritis and Infections

Infection and Autoimmunity, 2004

Publisher Summary Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characteri... more Publisher Summary Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by a symmetric inflammation and destruction of joints. Despite of large efforts and technology, the etiology of RA remains elusive, although it appears that genetic, infectious, environmental, and hormonal factors are all involved in complex interrelated ways. One of the most exciting areas of investigation is the application of Polymerase Chain Reaction (PCR). This technique is useful to the detection of bacterial and viral DNA in patients with RA. With PCR technique, foreign antigens of bacteria, virus, and superantigens can be found in the synovial fluid. In addition, the lymphocytes from synovial fluid can develop a local immune response stimulated by microorganisms such as Proteus mirabilis and Epstein-Barr virus. These lymphocyte responses were higher with these microorganisms than with other stimuli. Those data suggest an immune-infectious cause for RA. However, the difficulty of separating pathogens from contaminants has hampered these studies. On the other hand, the presence of foreign antigens is not specific for RA. Therefore, the role of these organisms in initiating and perpetuating inflammation in RA remains unknown; however, it continues to be actively investigated. This chapter provides an update on the various mechanisms in which infectious agents may play a role as inciting or perpetuating factors in the pathogenesis of RA.

Clinical spectrum of males with primary antiphospholipid syndrome and systemic lupus erythematosus: a comparative study of 73 patients

Lupus, 2004

The objective of this study was to compare the clinical findings, laboratory data, functional out... more The objective of this study was to compare the clinical findings, laboratory data, functional outcome and chronic damage in male patients with primary antiphospholipid syndrome (PAPS) and systemic lupus erythematosus (SLE). We studied 29 male patients with PAPS and 44 with SLE. Clinical findings, laboratory data, lupus damage index (SLICC/ACR DI), and functional outcome in PAPS, were analysed in each group. The mean age at diagnosiswas 29.8 + 10.4 years in patientswith PAPS and 26 + 10.1 years in SLE patients. The duration of disease was 4.5 + 2.6 versus 5.2 + 3.8 years in patients with PAPS and SLE, respectively(P NS). In patients with PAPS the most frequent clinical manifestations were venous thrombosis, thrombocytopenia, and pulmonary thromboembolism. Patients with SLE had joint, skin and renal involvement more frequently than those with PAPS (P 0.0001). All PAPS patients had anticardiolipin antibodies (aCL), and 14 patients (48%) had lupus anticoagulant (LA). All SLE patients ha...

The impact of gender on clinical manifestations of primary antiphospholipid syndrome

Lupus, 2005

The objective of the study was to determine the clinical differences at diagnosis and during foll... more The objective of the study was to determine the clinical differences at diagnosis and during follow-up between male and female patients with primary antiphospholipid syndrome (PAPS). We analysed 68 patients, 30 males and 38 females diagnosed and followed between 1990 and 2003. Patients with antiphospholipid syndrome associated with systemic lupus erythematosus at onset and during follow-up were excluded. The mean age at diagnosis was 31.4 ± 11 years in males and 35.7 ± 11 years in females (NS). The follow-up after diagnosis was 8.7 ± 3.1 years in males and 9.2 ± 2.9 years in females (NS). We did not find significant differences between the two groups with respect to venous and arterial thrombosis. However, in female patients, stroke was more prevalent than in male patients (12/38 versus 3/30, P = 0.03). In contrast, we found a significant prevalence of severe gastrointestinal complications in male compared to female patients (7/30 versus 1/38, P = 0.009). One male patient died due t...

Endothelial dysfunction in patients with antiphospholipid syndrome assessed with positron emission tomography

Journal of Nuclear Cardiology, 2007

There is limited knowledge about endothelial dysfunction in patients with primary antiphospholipi... more There is limited knowledge about endothelial dysfunction in patients with primary antiphospholipid syndrome (PAPS). The purpose of this study was to evaluate endothelial function in patients with PAPS assessed by positron emission tomography. A 3-phase protocol--rest, cold pressor test (CPT), and adenosine positron emission tomography with nitrogen 13 ammonia--was used in 18 patients with PAPS and 18 healthy volunteers (HVs). Myocardial blood flow (MBF) was measured in each phase, with calculation of the endothelial-dependent vasodilation index, the increase in the MBF in response to CPT, and the myocardial flow reserve. An important trend was found in the myocardial flow reserve (2.76 +/- 1.04 in PAPS group vs 3.27 +/- 0.72 in HV group, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; .05), in the endothelial-dependent vasodilation index (1.19 +/- 0.31 in PAPS group vs 1.55 +/- 0.37 in HV group, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05), and in the percent change in the MBF in response to CPT (from rest) (19% +/- 31% in PAPS group vs 55% +/- 37% in HV group, P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; .05). The CPT results obtained in this study showed that the PAPS patients studied have endothelial dysfunction.