Performance of the 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria for IgG4-Related Disease in a Latin American Cohort.

BACKGROUND/OBJECTIVE: The 2019 American College of Rheumatology/European League Against Rheumatism Classification Criteria (2019 AECC) for IgG4-related disease (IgG4-RD) is considered a significant advancement in the study of this condition. Most studies evaluating their performance have focused on White and Asian patients, leaving a knowledge gap regarding Latin American populations. Therefore, this study aimed to assess the performance of the 2019 AECC for IgG4-RD in a cohort of Latin American patients. METHODS: A multicenter medical records review study was conducted, involving centers from Argentina, Chile, Mexico, Peru, and Uruguay. Data on IgG4-RD patients and mimicker conditions were collected through a standardized online form. The criterion standard for diagnosing IgG4-RD was based on the fulfillment of the Comprehensive Diagnostic Criteria for IgG4-RD and/or the Consensus Statement on Pathology. The 2019 AECC was retrospectively applied. RESULTS: We included 300 patients, with 180 (60%) having IgG4-RD and 120 (40%) having mimicker conditions. The 2019 AECC had a sensitivity of 66.7% and a specificity of 100%. Sensitivity increased to 73.3% when disease-specific autoantibody items were removed, without affecting specificity. The true-positive cases had more involved organs, a higher availability of biopsy results, and were more likely to belong to the Mikulicz/systemic and proliferative phenotypes. CONCLUSIONS: The use of the 2019 AECC for IgG4-RD in a Latin American population confirms its high specificity in excluding those without the disease. The presence of concomitant autoimmune diseases and clinically nonsignificant disease-specific autoantibodies excludes a significant number of patients from fulfilling the criteria.

Digital Narratives of Living With Lupus: Lived Experiences and Meanings for Latin American and Latino Patients and Their Families.

OBJECTIVE: Systemic lupus erythematosus (SLE) disproportionately affects Latin American and Latino populations, with worse outcomes compared to nonminority populations. Understanding patients' views is critical to provide culturally competent care. The objective of this research is to analyze lived experiences with SLE from comments made by Latin American and Latino patients, and their relatives and friends, on the public Facebook group "Hablemos de Lupus" (in English: "Let's Talk about Lupus"). METHODS: Deidentified narratives posted as a reaction to the most popular resources shared by the page were extracted using the Facepager application. We conducted a thematic analysis under an interpretative medical anthropology framework. RESULTS: Five core themes were demonstrated by social media comments: lived experiences with lupus, religious/spiritual thoughts, metaphors, heredity, and experiences of family and friends. Being diagnosed with lupus is perceived as a life-changing event. The fluctuating course of the disease causes uncertainty, and the perception of invisibility within the patient's social circle generates feelings of being misunderstood. Faith and spiritual thoughts are coping strategies. Patients use metaphors about the disease's meaning and their lived experiences (the purple butterfly, not belonging, bellicose metaphors) to communicate with others. Relatives and friends are impacted by their loved one's distress. CONCLUSION: Patients perceive lupus as an unpredictable illness and use metaphors to foster empathy and communicate their experiences to others. Religion is as important as medical treatment to cope with the disease, and the experience of having lupus extends to family and friends. Findings can be used to improve physician-patient communication and lupus education campaigns in the Latin American and Latino population.

Clinical and Serological Features in Latin American IgG4-Related Disease Patients Differ According to Sex, Ethnicity, and Clinical Phenotype.

BACKGROUND/OBJECTIVE: Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD. METHODS: We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation. RESULTS: The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance. CONCLUSIONS: Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype.

A longitudinal multiethnic study of biomarkers in systemic lupus erythematosus: Launching the GLADEL 2.0 Study Group.

Introduction: After more than 20 years of sustained work, the Latin American Group for the Study of Lupus (GLADEL) has made a significant number of contributions to the field of lupus, not only in the differential role that race/ethnicity plays in its course and outcome but also in several other studies including the beneficial effects of using antimalarials in lupus patients and the development of consensus guidelines for the treatment of lupus in our region. Methods: A new generation of "Lupus Investigators" in more than 40 centers throughout Latin America has been constituted in order to continue the legacy of the investigators of the original cohort and to launch a novel study of serum and urinary biomarkers in patients with systemic lupus erythematosus. Results: So far, we have recruited 807 patients and 631 controls from 42 Latin-American centers including 339 patients with SLE without renal involvement, 202 patients with SLE with prevalent but inactive renal disease, 176 patients with prevalent and active renal disease and 90 patients with incident lupus nephritis. Conclusions: The different methodological aspects of the GLADEL 2.0 cohort are discussed in this manuscript, including the challenges and difficulties of conducting such an ambitious project.

Hidroxicloroquina en el tratamiento del COVID-19: como utilizarla a la espera de evidencia científica concluyente / Hydroxychloroquine in the treatment of COVID-19: how to use it waiting for conclusive scientific evidence

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An electrochemical biosensor for rapid detection of anti-dsDNA antibodies in absolute scale.

Autoimmune diseases are chronic inflammatory pathologies that are characterized by the presence of antibodies against the body's own epitopes in serum (autoantibodies). Systemic lupus erythematosus (SLE) is a common autoimmune pathology characterized by the presence of antinuclear antibodies (ANAs). These include anti-dsDNA (α-dsDNA) antibodies, which are widely used for diagnosis and disease monitoring. Their determination is carried out using traditional techniques such as Indirect Immunofluorescence (IFI) or Enzyme-Linked Immunosorbent Assay (ELISA), which are time consuming, require qualified technicians, and are not compatible with decentralized analysis outside a laboratory facility. Here, we show a sandwich-format electrochemical biosensor-based method for α-dsDNA determination in a rapid and simple manner. The total assay time is only 30 minutes, and the sensor is capable of detecting 16 ng (8 µg mL-1) of α-dsDNA antibodies. Using the current derived from the detection limit of the method as a cut-off, we could discriminate positive from negative serum samples with 90% sensitivity and 100% specificity. Using monoclonal antibodies for calibration curves, our results are presented in absolute scale (i.e., concentration instead of serum titer) which will help us to perform comparisons between methods and carry out further improvements of this protocol. In an effort to render the sensor compatible with automation, we minimized the manipulation steps without compromising the analytical performance, even in complex samples such as serum.

Pro-inflammatory Ca++-activated K+ channels are inhibited by hydroxychloroquine.

Antimalarials have demonstrated beneficial effects in Systemic Lupus Erithematosus and Rheumatoid Arthritis. However, the mechanisms and the molecular players targeted by these drugs remain obscure. Although hydroxychloroquine (HCQ) is a known ion channel inhibitor, this property has not been linked to its anti-inflammatory effects. We aimed to study whether HCQ inhibits pro-inflammatory ion channels. Electrophysiology experiments demonstrated that HCQ inhibited Ca++-activated K+ conductance in THP-1 macrophages in a dose-dependent manner. In macrophages, ATP-induced K+ efflux plays a key role in activating the NLRP3 inflammasome. ATP-induced IL-1beta secretion was controlled by the KCa1.1 inhibitor iberiotoxin. NS1619 and NS309 (KCa1.1 and KCa3.1 activators respectively) induced the secretion of IL-1beta. This effect was inhibited by HCQ and also by iberiotoxin and clotrimazol (KCa3.1 inhibitor), arguing against off-target effect. In vitro, HCQ inhibited IL-1beta and caspase 1 activation induced by ATP in a dose-dependent manner. HCQ impaired K+ efflux induced by ATP. In vivo, HCQ inhibited caspase 1-dependent ATP-induced neutrophil recruitment. Our results show that HCQ inhibits Ca++-activated K+ channels. This effect may lead to impaired inflammasome activation. These results are the basis for i) a novel anti-inflammatory mechanism for HCQ and ii) a new strategy to target pro-rheumatic Ca++-activated K+ channels.

Renal transplantation in systemic lupus erythematosus: outcome and prognostic factors in 50 cases from a single centre.

BACKGROUND: End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). OBJECTIVES: To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. RESULTS: Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36±10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. CONCLUSION: Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure.