Myositis-Specific Antibodies and Myositis-Associated Antibodies in Patients With Idiopathic Inflammatory Myopathies From the PANLAR Myositis Study Group.

BACKGROUND: Dermatomyositis (DM) and polymyositis (PM) are forms of idiopathic inflammatory myopathies (IIMs), which are associated with the production of autoantibodies that are useful in the diagnosis and prognosis of the disease. OBJECTIVE: The aim of this study was to determine the frequency of antinuclear autoantibodies (ANAs), myositis-specific autoantibodies (MSAs), and myositis-associated autoantibodies (MAAs) in 6 Latin American countries. METHODS: Two hundred ten patients with IIM were included in this cross-sectional study from 2014 to 2017: 112 from Mexico, 46 from Colombia, 20 from Peru, 16 from the Dominican Republic, 10 from Argentina, and 6 from Guatemala. Antinuclear autoantibodies were detected by indirect immunofluorescence on HEp-2 cells. MSAs and MAAs were tested by a line immunoassay method. Mann-Whitney U and χ2 tests were used for statistical analysis. RESULTS: Of the 210 IIM patients, 139 (66.2%) had DM, 59 (28%) PM, and 12 (5.7%) juvenile DM. The mean age was 43.5 (6-79 years); 158 (75.2%) were female, and 52 (24.8%) were male. The overall frequency of ANA was 60%. The most frequent patterns were fine speckled (AC-4) (78.3%) and cytoplasmic (AC-19) (6.45%). The most frequent MSA were anti-Mi-2 (38.5%) and anti-Jo-1 (11.9%). Anti-Mi-2 was more frequent in patients from Colombia (40.1%). The MAA more frequent were anti-Ro-52/TRIM21 (17.6%) and anti-PM-Scl75 (7.5%). CONCLUSIONS: This is the first study of ANA, MSA, and MAA in patients from 6 countries from the Panamerican League against Rheumatism myositis study group. We observed a general prevalence of 60% of ANA. In relation to MSA and MAA, anti-Mi-2 was the more frequent (38.5%).

Autoantibodies to Mi-2 alpha and Mi-2 beta in patients with idiopathic inflammatory myopathy.

OBJECTIVES: The objective of this study was to compare the results obtained from different assays for the detection of anti-Mi-2 antibodies, which are important markers in the diagnosis of DM. METHODS: The study included 82 patients (68 females/14 males), most of whom had DM (n = 57), followed by PM (n = 16) and juvenile DM (n = 9). All samples were tested using a novel particle-based multi-analyte technology (PMAT) (Inova Diagnostics, research use only) in parallel with a line immunoassay (LIA: Euroimmun). To assess clinical specificity for the PMAT assay, a total of 775 disease and healthy controls were tested. RESULTS: 29 samples were positive by at least one test for anti-Mi-2 antibodies. Of those, 24 were Mi-2ß LIA+, five were Mi-2α LIA+ and 23 Mi-2 PMAT+. The comparison shows varying agreement between the different methods (kappa 0.27-0.77). When LIA results were used as reference for receiver operating characteristics analysis, high area under the curve values were found for both PMAT vs LIA Mi-2α and LIA Mi-2ß. When analysing the results in the context of the myositis phenotype, PMAT associated closest with the DM phenotype. In the control group, 3/775 controls (all low levels) were anti-Mi-2+ resulting in a sensitivity and specificity of 28.1% and 99.6%, respectively. CONCLUSION: Overall, good agreement was found between LIA and PMAT for anti-Mi-2 antibodies, which is important for the standardization of autoantibodies. Anti-Mi-2ß antibodies measured by PMAT tend be more highly associated with the clinical phenotype of DM.

Genetic Alleles Associated with SLE Susceptibility and Clinical Manifestations in Hispanic Patients from the Dominican Republic.

PURPOSE: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with marked disparities in prevalence and disease severity among different ethnic groups. The purpose of this study is to characterize a Latin American cohort and identify genetic risk factors for developing SLE and its end-organ manifestations in this Latin Hispanic cohort. METHODS: A total of 201 SLE cases and 205 non-diseased controls were recruited in the Dominican Republic (DR). Cases were defined according to the 1997 revised American College of Rheumatology criteria for the classification of SLE. Genomic DNA was prepared from whole blood and applied to genotyping analyses for 42 single nucleotide polymorphisms (SNPs) that have been implicated in autoimmune diseases, including SLE, in other ethnic populations. Data were analyzed by Fisher's Exact Probability Test. RESULTS: In this cohort, SNP rs9271366 (tag SNP for HLA-DRB1*15:01) confers the highest risk for SLE among the 13 MHC gene alleles that display association with SLE (p = 8.748E-10; OR = 3.5). Among the 26 non-MHC gene alleles analyzed, SNP rs2476601 in PTPN22 gene confers the highest risk for SLE (p = 0.0001; OR = 5.6). ITGAM, TNFSF4, TNIP1, STAT4, CARD11, BLK, and TNXB gene alleles were confirmed as SLE-susceptible alleles in the DR cohort. However, IRF5 and TNFAIP3 gene alleles, established risk factors for SLE in populations of European and Asian ancestry, are not significantly associated with SLE in this cohort. We also defined a novel HLA-DRA haplotype that confers an increased risk for lupus nephritis (LN) and alleles in HLA-DRA2 and TNFSF4 genes as genetic risk factors for developing neuropsychiatric (NP) SLE. CONCLUSION: Our data suggest that the Latin American population shares some common genetic risk factors for SLE as other populations, but also has distinct risk gene alleles that contribute to SLE susceptibility and development of LN and NPSLE. This is the first study focusing on genetic risk factors for SLE in the DR, a Latin American population that has never been characterized before.

Rituximab in the treatment of inflammatory myopathies: a review.

Several uncontrolled studies have encouraged the use of rituximab (RTX) in patients with myositis. Unfortunately, the first placebo-phase trial to assess the efficacy of RTX in refractory myositis did not show a significant difference between the two treatment groups, and doubts have been expressed about its study design. In this review we present an up-to-date overview of the reported experiences of RTX therapy in myositis. A PubMed search was performed to find all the available cases of refractory myositis patients treated with RTX up to July 2015. The following terms were assessed: inflammatory myopathies OR anti-synthetase syndrome OR polymyositis OR dermatomyositis AND RTX. A total of 48 studies were included. We identified 458 patients with myositis treated with RTX. We found a rate of response to RTX of 78.3%. RTX can play a role in the management of patients with myositis, at least in those with positive myositis-specific autoantibodies.

Esclerodermia en el Caribe: características en una serie de casos dominicana / Scleroderma in the caribbean: characteristics in a dominican case series

Introducción. La esclerodermia es una enfermedad rara, de la cual existe información limitada en América Latina. Estudios preliminares en genética muestran que la ascendencia de República Dominicana tiene fuerte influencia africana, lo cual podría modular la expresión de la enfermedad. El propósito de este estudio es describir las características clínicas y demográficas de esclerodermia en una serie de pacientes dominicanos. Materiales y métodos. Se seleccionaron los pacientes que cumplieron con los criterios del EULAR/ACR para esclerosis sistémica de la base de datos del servicio de reumatología de un centro terciario. Se definieron los subtipos de esclerodermia de acuerdo a la clasificación EULAR. La información clínica y demográfica al momento del diagnóstico fue obtenida de forma retrospectiva de los expedientes médicos. Resultados. La prevalencia fue estimada de 9,3 por millón de habitantes. Veinte y seis pacientes entraron al estudio. La edad media al momento del primer síntoma fue 32,6 ± 15 años; el 68% de los pacientes tenía 40 años de edad o menos cuando aparecieron los síntomas. El 73,1% de los pacientes fue de sexo femenino, con una relación mujer:hombre 2,7:1. Los sistemas orgánicos más afectados fueron el pulmonar y el gastrointestinal; la afectación renal fue rara. Los anticuerpos anti-Scl-70 se encontraron positivos en el 64% de los casos y, en 2 casos, en coexistencia con anticentrómero. Conclusiones. La prevalencia de esclerosis sistémica es menor en la población dominicana que la reportada internacionalmente. La edad de inicio de la enfermedad parece ser menor en la población dominicana que la reportada en la literatura. Un patrón distinto de autoanticuerpos es observado en esta población (AU)

Introduction. Scleroderma is a rare disease with limited data in Latin America. Preliminary genetic studies suggest a strong African ascendance in the Dominican Republic, which could modulate the expression of the disease. The objective of this study is to describe the clinical and demographic characteristics of scleroderma in a series of 26 Dominican patients. Materials and methods. Patients who fulfilled the EULAR/ACR criteria for scleroderma were selected from the Rheumatology Department of a tertiary health center; systemic sclerosis subtypes were defined according to the EULAR classification. Clinical and demographic information was obtained retrospectively from clinical records. Results. Mean age at time of onset was 32.6±15 years; 68% of patients had 40 years of age or less. 73% of patients were females, with a female:male ratio of 2.7:1. The most affected systems were pulmonary and gastrointestinal; renal affection was scarce. Anti-Scl-70 antibodies were positive in 64% of patients, sometimes in coexistence with anti-centromere antibodies. Conclusions. The prevalence of systemic sclerosis is lower in the Dominican population than was reported elsewhere. The age of onset of the disease seems to be lower in the Dominican population than that reported in literature. A different pattern of autoantibodies is observed in this population (AU)

Scleroderma in the Caribbean: characteristics in a Dominican case series.

INTRODUCTION: Scleroderma is a rare disease with limited data in Latin America. Preliminary genetic studies suggest a strong African ascendance in the Dominican Republic, which could modulate the expression of the disease. The objective of this study is to describe the clinical and demographic characteristics of scleroderma in a series of 26 Dominican patients. MATERIALS AND METHODS: Patients who fulfilled the EULAR/ACR criteria for scleroderma were selected from the Rheumatology Department of a tertiary health center; systemic sclerosis subtypes were defined according to the EULAR classification. Clinical and demographic information was obtained retrospectively from clinical records. RESULTS: Mean age at time of onset was 32.6±15 years; 68% of patients had 40 years of age or less. 73% of patients was feminine, with a female:male ratio of 2.7:1. The most affected systems were pulmonary and gastrointestinal; renal affection was scarce. Anti-Scl-70 antibodies were positive in 64% of patients, sometimes in coexistence with anti-centromere antibodies. CONCLUSIONS: The prevalence of systemic sclerosis is lower in the Dominican population than the reported elsewhere. The age of onset of the disease seems to be lower in the Dominican population than that reported in literature. A different pattern of autoantibodies is observed in this population.

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.