Gonococcal arthritis in a healthy adult. Is it that possible?

A case report is presented of a 50-year-old woman who was seen in Accident and Emergency because of pain in the lumbar area. She was subsequently diagnosed with septic arthritis of the left hip due to being Neisseria gonorrhoeae positive for beta-lactamase. She responded to treatment with ceftriaxone, but later required a total hip replacement.

Presentamos el caso de una mujer de 50 arios, sin antecedentes de importancia, a quien se le diagnosticó inicialmente lumbago e infección de vías urinarias. Por persistencia del dolor y limitación de la movilidad en la cadera izquierda se inicia el estudio de artritis séptica, que fue provocada por Neisseria gonorrhoeae betalactamasa positiva, sensible a tratamiento con ceftriaxona, con posterior deterioro articular, el cual requirió reemplazo total de cadera.

Safety and efficacy of convalescent plasma for severe COVID-19: a randomized, single blinded, parallel, controlled clinical study.

BACKGROUND: Convalescent plasma (CP) has been widely used to treat COVID-19 and is under study. However, the variability in the current clinical trials has averted its wide use in the current pandemic. We aimed to evaluate the safety and efficacy of CP in severe coronavirus disease 2019 (COVID-19) in the early stages of the disease. METHODS: A randomized controlled clinical study was conducted on 101 patients admitted to the hospital with confirmed severe COVID-19. Most participants had less than 14 days from symptoms onset and less than seven days from hospitalization. Fifty patients were assigned to receive CP plus standard therapy (ST), and 51 were assigned to receive ST alone. Participants in the CP arm received two doses of 250 mL each, transfused 24 h apart. All transfused plasma was obtained from "super donors" that fulfilled the following criteria: titers of anti-SARS-CoV-2 S1 IgG ≥ 1:3200 and IgA ≥ 1:800 antibodies. The effect of transfused anti-IFN antibodies and the SARS-CoV-2 variants at the entry of the study on the overall CP efficacy was evaluated. The primary outcomes were the reduction in viral load and the increase in IgG and IgA antibodies at 28 days of follow-up. The per-protocol analysis included 91 patients. RESULTS: An early but transient increase in IgG anti-S1-SARS-CoV-2 antibody levels at day 4 post-transfusion was observed (Estimated difference [ED], - 1.36; 95% CI, - 2.33 to - 0.39; P = 0.04). However, CP was not associated with viral load reduction in any of the points evaluated. Analysis of secondary outcomes revealed that those patients in the CP arm disclosed a shorter time to discharge (ED adjusted for mortality, 3.1 days; 95% CI, 0.20 to 5.94; P = 0.0361) or a reduction of 2 points on the WHO scale when compared with the ST group (HR adjusted for mortality, 1.6; 95% CI, 1.03 to 2.5; P = 0.0376). There were no benefits from CP on the rates of intensive care unit admission (HR, 0.82; 95% CI, 0.35 to 1.9; P = 0.6399), mechanical ventilation (HR, 0.66; 95% CI, 0.25 to 1.7; P = 0.4039), or mortality (HR, 3.2; 95% CI, 0.64 to 16; P = 0.1584). Anti-IFN antibodies and SARS-CoV-2 variants did not influence these results. CONCLUSION: CP was not associated with viral load reduction, despite the early increase in IgG anti-SARS-CoV-2 antibodies. However, CP is safe and could be a therapeutic option to reduce the hospital length of stay. Trial registration NCT04332835.

Factors Associated With Diagnostic Delay of Axial Spondyloarthritis in Colombian Patients.

BACKGROUND/OBJECTIVE: The diagnostic delay of axial spondyloarthritis (axSpA) is globally reported to be between 3 and 11 years. Early diagnosis and treatment have long-term benefits for patients and the health care system. Several international studies have evaluated some factors associated with diagnostic delay, but there are no known studies in the Colombian population. This study assesses the factors associated with diagnostic delay of axSpA in a rheumatology center in Bogota, Colombia. METHODS: This monocentric analytical cross-sectional study was done in a specialized rheumatology center. Patients who fulfilled the 2009 Assessment of Spondyloarthritis International Society (ASAS) classification criteria for axSpA were included. Information was obtained from medical records and a phone call. Bivariate and multivariate analyses were done to assess the associated factors with diagnostic delay. RESULTS: One hundred one patients were included, 54 were women (53.5%). The median diagnostic delay was 2 years (interquartile range, 1-7). The bivariate analysis showed that a younger age at diagnosis (p = 0.042) and previous diagnosis of lumbar degenerative disease (p = 0.029) were associated with a longer diagnostic delay. The logistical regression showed that previous lumbar degenerative disc disease (odds ratio, 2.8; 95% confidence interval, 1.09-7.53) and fibromyalgia (odds ratio, 4.0; 95% confidence interval, 1.2-13.1) diagnosis were both associated with a longer diagnostic delay. CONCLUSIONS: Factors associated with a longer diagnostic delay were previous diagnosis of lumbar degenerative disc disease and fibromyalgia. Additional studies are needed so that the reasons for diagnostic delay are understood and early diagnosis and management of axSpA are enabled.

New insights into the taxonomy of autoimmune diseases based on polyautoimmunity.

OBJECTIVE: The clinical coexistence of two or more autoimmune diseases (ADs) fulfilling classification criteria is termed "overt polyautoimmunity" (PolyA), whereas the presence of autoantibodies unrelated to an index AD, without clinical criteria fulfillment, is known as "latent PolyA". We aimed to explore a new taxonomy of ADs based on PolyA. METHODS: In a cross-sectional study of 292 subjects, we evaluated the presence of PolyA in 146, 45, 29, 17, and 17 patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), autoimmune thyroid disease (AITD) and systemic sclerosis (SSc), respectively, and 38 healthy controls. Clinical assessment, autoantibody profile (by autoantigen array chip), lymphocytes immunophenotype and cytokine profile (by flow cytometry) were evaluated simultaneously. A mixed cluster methodology was used to classify ADs. RESULTS: Latent PolyA was more frequent than overt PolyA, ranging from 69.9% in RA to 100% in SSc. Nevertheless, both latent and overt PolyA clustered together. Over-expressed IgG autoantibodies were found to be hallmarks for the identification of index ADs. The combination of autoantibodies allowed high accuracy in the classification of ADs. Three well-defined clusters based on PolyA were observed with distinctive clinical and immunological phenotypes. CONCLUSIONS: This proof-of-concept study indicates that ADs can be classified according to PolyA. PolyA should be considered in all studies dealing with ADs, including epidemiological, genetic, and clinical trials.

Polymyalgia rheumatica: A case series from Colombia and analysis of Latin America.

OBJECTIVE: Polymyalgia rheumatica (PMR) is the most common inflammatory disease in patients over 50 years. Information about the disease in Latin America (LATAM) is scarce. We aimed to evaluate a group of Colombian patients with PMR and to conduct a systematic review of PMR in LATAM. METHODS: A multicentric retrospective study was performed. Medical records of 256 PMR patients were evaluated. Patients were divided into two groups, those fulfilling the 2012 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for PMR and those who did not (i.e., clinical diagnosis). A systematic literature review and meta regression was performed comparing Colombian vs LATAM patients. RESULTS: From 256 patients, 145 (56.6%) fulfilled the 2012 EULAR/ACR criteria, and 111 (43.3%) were classified by clinical diagnosis. Inflammatory bilateral shoulder pain, pelvic girdle aching, morning stiffness >45 min, elevated erythrocyte sedimentation rate (ESR), and C-reactive protein (CPR), and Methotrexate (MTX) prescription were more common in the 2012 EULAR/ACR group. None of the included patients presented overt polyautoimmunity (PolyA), whereas up to 24% exhibited latent PolyA. In addition, these patients showed high frequency of malignancy (7.59%). In the meta regression analysis, Colombian patients exhibited lower ESR levels, and were less likely to develop giant cell arteritis (GCA) as compared to the rest of LATAM data. CONCLUSION: Patients with PMR in LATAM exhibit similar phenotypes from other cohorts worldwide. Malignancy, GCA and latent PolyA should be considered in the routine clinical follow-up of patients with PMR.

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%).

Convalescent plasma in Covid-19: Possible mechanisms of action.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible of the coronavirus disease 2019 (COVID-19) pandemic. Therapeutic options including antimalarials, antivirals, and vaccines are under study. Meanwhile the current pandemic has called attention over old therapeutic tools to treat infectious diseases. Convalescent plasma (CP) constitutes the first option in the current situation, since it has been successfully used in other coronaviruses outbreaks. Herein, we discuss the possible mechanisms of action of CP and their repercussion in COVID-19 pathogenesis, including direct neutralization of the virus, control of an overactive immune system (i.e., cytokine storm, Th1/Th17 ratio, complement activation) and immunomodulation of a hypercoagulable state. All these benefits of CP are expected to be better achieved if used in non-critically hospitalized patients, in the hope of reducing morbidity and mortality.

Vogt-Koyanagi-Harada disease. Case report and review of the literature / Enfermedad de Vogt Koyanagi Harada. Reporte de un caso y revisión de la literatura

ABSTRACT Vogt Koyanagi Harada disease affects several parts of the body, such as eyes, meninges, ears, and skin. The progressive course of the disease can lead to blindness and deafness. The case is presented of a Hispanic woman (mixed-race) with visual alterations, headache, tinnitus, hearing loss, and posterior uveitis with serous detachments of the retina in both eyes, as well as lymphocytic meningitis. The aim of the present study is to review the literature, the diagnostic strategies, and the appropriate treatment, as well as to update the immunogenetic pathogenesis of the disease.

RESUMEN La enfermedad de Vogt Koyanagi Harada compromete múltiples órganos tales como ojos, meninges, oídos y piel. El curso progresivo de la enfermedad puede llevar a ceguera y cofosis. Se describe un caso de esta enfermedad en mujer hispana (mestiza) con alteraciones visuales, cefalalgia, tinnitus e hipoacusia a quien se le encuentra uveítis posterior con desprendimientos serosos de retina en ambos ojos y meningitis linfocitaria. El objetivo del presente estudio es, mediante una revisión de la literatura, actualizar la patogénesis inmunogenética, conocer las estrategias diagnósticas y el tratamiento apropiado.

Cytokine imbalance in patients with systemic sclerosis and resilience: the key role of interleukin-6.

OBJECTIVES: Resilience, the ability to respond positively to adverse events, may be influenced by long-term stressors and autoimmune/inflammatory conditions such as systemic sclerosis (SSc). Since the immune system plays a role in the development of resilience, we aimed to evaluate the relationship between a panel of cytokines and resilience in patients with SSc. METHODS: Thirty-five consecutive women with established SSc were involved in this exploratory study. Clinical characteristics, including severity of symptoms and resilience, a panel of 15 serum cytokines and 17 autoantibodies were assessed simultaneously. Multivariate methods were used to analyse the data. RESULTS: Interleukin-6 (IL-6) levels were associated with severity of symptoms (ß=1.8395, p=0.04), and low resilience scores (ß= -0.581120, p=0.02). Furthermore, resilience was not associated with clinical manifestations nor polyautoimmunity. Cytokine levels did not significantly differ between groups based on regular physical activity. CONCLUSIONS: The results highlight the importance of IL-6 as a key mediator in the altered cytokine network of SSc.

Subcutaneous abatacept in rheumatoid arthritis: A real-life experience.

OBJECTIVES: To assess the effectiveness, safety, and drug survival of subcutaneous (SC) abatacept (ABA) in a cohort of rheumatoid arthritis (RA) patients in a real-world setting. METHODS: This was a retrospective cohort study from 2014 to 2018 in which patients with RA (1987 ACR criteria) were included. Patients were evaluated at a single rheumatology outpatient center in Bogotá, Colombia. The patients were classified according to their treatment background: biological-naïve (n = 65), switched from IV to SC ABA administration (125 mg-wk) (n = 32), and inadequate response to biological DMARD (n = 62). The primary endpoint was a change in DAS28-CRP and RAPID3 from baseline to 12 months. A linear mixed effect model was used to correlate repeated measures. Adverse events were assessed and recorded during each visit to the rheumatology center. Several Cox proportional hazard regression models were used to test if there were any differences in drug survival curves based on seropositivity for rheumatoid factor (RF), and anti-Cyclic Citrullinated Peptide Antibodies (anti-CCP). Statistical analysis was done using software R version 3.4.4. RESULTS: A total of 159 patients were included. Baseline characteristics of patients were as follows: female gender 84%, median age of 54 years (IQR 16), median disease duration 10 years (11), RF positive 96%, anti-CCP positive 89%, erosive disease 55%, median DAS28-CRP 5.0 (2), and median RAPID3 17 (10). Concomitant use of methotrexate and SC ABA monotherapy were reported at 52% and 30% respectively. Demographics and disease characteristics were similar for all groups, except for baseline DAS28-CRP, and RAPID3 in the group that switched route of administration. The interaction between time and group was significant (p = 0.0073) for RAPID3. Infections, constitutional symptoms, and headaches were the most frequent AEs. Retention rate corresponded to 60% at 48 months. The most frequent reason for drug suspension was loss of efficacy. Median time of treatment for SC ABA was 31 months (IQR 30). The only association that reached statistical significance was anti-CCP concentration [Q1-Q4] (p = 0.005). According to the Cox proportional hazard regression model, there were significant differences between survival curves for Q1 (HR 0.15; 0.03-0.64 95% CI; p = 0.0096), and Q2 (HR 0.28; 0.08-0.92 95% CI; p = 0.0363) compared to the seronegative group. CONCLUSIONS: The results showed an improvement in RA disease activity and physical function in patients under SC ABA treatment. Patients switching from IV to SC administration of ABA had lower activity and functional impairment at baseline. SC ABA demonstrated a good safety profile consistent with previously published data. Patients with baseline levels of anti-CCP antibody concentrations had better drug survival than seronegative patients.

Sjögren's Syndrome and Autoimmune Thyroid Disease: Two Sides of the Same Coin.

The coexistence of Sjögren's syndrome (SS) and autoimmune thyroid disease (AITD) has been documented. However, there is no consensus whether this coexistence should be considered as the same nosological condition or as polyautoimmunity. Thus, in this monocentric retrospective study, patients with SS alone (i.e., primary) were compared with patients with SS and AITD. In addition, a discussion of previous studies including those about genetic and environmental factors influencing the development of both conditions is presented. In our series, all patients with AITD had Hashimoto's thyroiditis (HT). No significant differences in age, gender, age of disease onset, and disease duration were found between the two groups. Lymphadenopathy and urticaria were more frequently registered in patients with SS-HT than in patients with SS alone (p < 0.05). Anti-Ro/SSA antibodies were more frequent in the primary SS group (p = 0.01). SS-HT patients were more likely to report a positive history of smoking (p = 0.03). The clinical expression of SS varies slightly when HT coexists. Although both entities share common physiopathological mechanisms as part of the autoimmune tautology, they are nosologically different and their coexistence should be interpreted as polyautoimmunity. Further studies based on polyautoimmunity would allow establishing a new taxonomy of autoimmune diseases.

Resilience in women with autoimmune rheumatic diseases.

OBJECTIVE: To evaluate the relationship between resilience and clinical outcomes in patients with autoimmune rheumatic diseases. METHODS: Focus groups, individual interviews, and chart reviews were done to collect data on 188 women with autoimmune rheumatic diseases, namely rheumatoid arthritis (n=51), systemic lupus erythematosus (n=70), systemic sclerosis (n=35), and Sjögren's syndrome (n=32). Demographic, clinical, and laboratory variables were assessed including disease activity by patient reported outcomes. Resilience was evaluated by using the Brief Resilience Scale. Bivariate, multiple linear regression, and classification and regression trees were used to analyse data. RESULTS: Resilience was influenced by age, duration of disease, and socioeconomic status. Lower resilience scores were observed in younger patients (<48years) with systemic lupus erythematosus, rheumatoid arthritis, and systemic sclerosis who had low socioeconomic status, whereas older patients (>50years) had higher resilience scores regardless of socioeconomic status. There was no influence of disease activity on resilience. A particular behaviour was observed in systemic sclerosis in which patients with high socioeconomic status and regular physical activity had higher resilience scores. CONCLUSION: Resilience in patients with autoimmune rheumatic diseases is a continuum process influenced by age and socioeconomic status. The ways in which these variables along with exercise influence resilience deserve further investigation.

Can Appropriate Systemic Treatment Help Protect the Cornea in Patients With Rheumatoid Arthritis? A Multidisciplinary Approach to Autoimmune Ocular Involvement.

PURPOSE: To correlate rheumatologic with ophthalmic and laboratory findings in patients with rheumatoid arthritis (RA) to identify what effect these have on development of ocular disease. METHODS: This is a cross-sectional study of 172 eyes of 86 patients with RA. Patients were examined by a group of rheumatologists. Sociodemographic, clinical, and laboratory data were collected. All patients underwent complete ophthalmologic examination including corneal topography and endothelial cell count. RESULTS: There was no significant correlation between RA-negative prognostic indicators (NPIs) and pathologic corneal findings. Patients using disease-modifying antirheumatic drugs (DMARDs) and antimalarial drugs had greater corneal volumes (mean difference 8.51 mm, 90% confidence interval [CI], 3.98-13.04, P = 0.004; and 2.24, 90% CI, 0.32-4.54, P = 0.048, respectively). Patients using azathioprine had lower endothelial cell counts compared with those using other drugs (mean difference 180 cells/mm, 90% CI, 69-291, P = 0.008). Patients using biologic DMARDs had better tear osmolarity values (between 280 and 300 mOsm/L) than patients not using them (mean difference 14.3 mOsm/L, P = 0.022). There was no correlation between NPIs of RA and positive keratoconus screening indices (Spearman correlation OD -0.013, P = 0.91; OS -0.033, P = 0.76). CONCLUSIONS: There was no clear correlation between RA-NPIs and pathologic corneal findings in our study. DMARDs treatment may help maintain corneal integrity in our patients and prevented collagenolytic manifestations of RA. Other medications such as azathioprine should be used carefully, as endothelial damage may potentially occur.

Interacciones entre citoquinas y resiliencia en pacientes con esclerosis sistémica / Interactions between Cytokines and resilience in patients with systemic sclerosis

Introducción: Resiliencia es la habilidad de responder de manera positiva a eventos adversos. Ésta puede ser influenciada por factores como el estrés crónico, la actividad física y afeccio-nes autoinmunes y/o inflamatorias como la esclerosis sistémica (ES) (1). Objetivo: Evaluar un panel de citoquinas y su asociación con resiliencia, severidad de los síntomas y actividad física en pacientes con ES. Métodos: Este fue un estudio exploratorio que incluyó 35 mujeres con ES. Las características clínicas, incluidas la severidad de los síntomas, la actividad física, la resiliencia así como un panel de 15 citoquinas fueron evaluados simultáneamente.

Cytokine and autoantibody clusters interaction in systemic lupus erythematosus.

BACKGROUND: Evidence supports the existence of different subphenotypes in systemic lupus erythematosus (SLE) and the pivotal role of cytokines and autoantibodies, which interact in a highly complex network. Thus, understanding how these complex nonlinear processes are connected and observed in real-life settings is a major challenge. Cluster approaches may assist in the identification of these subphenotypes, which represent such a phenomenon, and may contribute to the development of personalized medicine. Therefore, the relationship between autoantibody and cytokine clusters in SLE was analyzed. METHODS: This was an exploratory study in which 67 consecutive women with established SLE were assessed. Clinical characteristics including disease activity, a 14-autoantibody profile, and a panel of 15 serum cytokines were measured simultaneously. Mixed-cluster methodology and bivariate analyses were used to define autoantibody and cytokine clusters and to identify associations between them and related variables. RESULTS: First, three clusters of autoantibodies were defined: (1) neutral, (2) antiphospholipid antibodies (APLA)-dominant, and (3) anti-dsDNA/ENA-dominant. Second, eight cytokines showed levels above the threshold thus making possible to find 4 clusters: (1) neutral, (2) chemotactic, (3) G-CSF dominant, and (4) IFNα/Pro-inflammatory. Furthermore, the disease activity was associated with cytokine clusters, which, in turn, were associated with autoantibody clusters. Finally, when all biomarkers were included, three clusters were found: (1) neutral, (2) chemotactic/APLA, and (3) IFN/dsDNA, which were also associated with disease activity. CONCLUSION: These results support the existence of three SLE cytokine-autoantibody driven subphenotypes. They encourage the practice of personalized medicine, and support proof-of-concept studies.

How is the ultrasound in rheumatology used, implemented, and applied in Latin American centers? Results from a multicenter study.

This study aimed to perform an overview of how ultrasound (US) is being used, implemented, and applied in rheumatologic centers in Latin America (LA). A retrospective, multicenter 1-year experience study was undertaken. Eighteen centers from eight countries were involved. The following information were collected: demographic data, indication to perform an US examination, physician that required the examination, and the anatomical region required for the examination. A total of 7167 patients underwent an US examination. The request for US examinations came most frequently from their own institution (5981 (83.45 %)) than from external referral (1186 (16.55 %)). The services that more frequently requested an US examination were rheumatology 5154 (71.91 %), followed by orthopedic 1016 (14.18 %), and rehabilitation 375 (5.23 %). The most frequently scanned area was the shoulder in 1908 cases (26.62 %), followed by hand 1754 (24.47 %), knee 1518 (21.18 %), ankle 574 (8.01 %), and wrist 394 (5.50 %). Osteoarthritis was the most common disease assessed (2279 patients (31.8 %)), followed by rheumatoid arthritis (2125 patients (29.65 %)), psoriatic arthritis (869 patients (12.1 %)), painful shoulder syndrome (545 (7.6 %)), connective tissue disorders (systemic sclerosis 339 (4.7 %), polymyositis/dermatomyositis 107 (1.4 %), Sjögren's syndrome 60 (0.8 %), and systemic lupus erythematosus 57 (0.8 %)). US evaluation was more frequently requested for diagnostic purposes (3981 (55.5 %)) compared to follow-up studies (2649 (36.9 %)), research protocols (339 (4.73 %)), and invasive guided procedures (198 (2.76 %)). US registered increasing applications in rheumatology and highlighted its positive impact in daily clinical practice. US increases the accuracy of the musculoskeletal clinical examination, influence the diagnosis, and the disease management.

Polyautoimmunity in Sjögren Syndrome.

Polyautoimmunity is defined as the presence of more than one well-defined autoimmune disease (AD) in a single patient. Polyautoimmunity is a frequent condition in Sjögren syndrome (SS) and follows a grouping pattern. The most frequent ADs observed in SS are autoimmune thyroid disease, rheumatoid arthritis, and systemic lupus erythematosus. Main factors associated with polyautoimmunity in SS are tobacco smoking and some genetic variants. The study of polyautoimmunity provides important clues for elucidating the common mechanisms of autoimmne diseases (ie, the autoimmune tautology).

Definition of mutations in polyautoimmunity.

OBJECTIVES: Familial autoimmunity and polyautoimmunity represent extreme phenotypes ideal for identifying major genomic variants contributing to autoimmunity. Whole exome sequencing (WES) and linkage analysis are well suited for this purpose due to its strong resolution upon familial segregation patterns of functional protein coding and splice variants. The primary objective of this study was to identify potentially autoimmune causative variants using WES data from extreme pedigrees segregating polyautoimmunity phenotypes. METHODS: DNA of 47 individuals across 10 extreme pedigrees, ascertained from probands affected with polyautoimmunity and familial autoimmunity, were selected for WES. Variant calls were obtained through Genome Analysis Toolkit. Filtration and prioritization framework to identify mutation(s) were applied, and later implemented for genetic linkage analysis. Sanger sequencing corroborated variants with significant linkage. RESULTS: Novel and mostly rare variants harbored in SRA1, MLL4, ABCB8, DHX34 and PLAUR showed significant linkage (LOD scores are >3.0). The strongest signal was in SRA1, with a LOD score of 5.48. Network analyses indicated that SRA1, PLAUR and ABCB8 contribute to regulation of apoptotic processes. CONCLUSIONS: Novel and rare variants in genetic linkage with polyautoimmunity were identified throughout WES. Genes harboring these variants might be major players of autoimmunity.

Familial Aggregation and Segregation Analysis in Families Presenting Autoimmunity, Polyautoimmunity, and Multiple Autoimmune Syndrome.

Studies documenting increased risk of developing autoimmune diseases (ADs) have shown that these conditions share several immunogenetic mechanisms (i.e., the autoimmune tautology). This report explored familial aggregation and segregation of AD, polyautoimmunity, and multiple autoimmune syndrome (MAS) in 210 families. Familial aggregation was examined for first-degree relatives. Segregation analysis was implemented as in S.A.G.E. release 6.3. Data showed differences between late- and early-onset families regarding their age, age of onset, and sex. Familial aggregation of AD in late- and early-onset families was observed. For polyautoimmunity as a trait, only aggregation was observed between sibling pairs in late-onset families. No aggregation was observed for MAS. Segregation analyses for AD suggested major gene(s) with no clear discernible classical known Mendelian transmission in late-onset families, while for polyautoimmunity and MAS no model was implied. Data suggest that polyautoimmunity and MAS are not independent traits and that gender, age, and age of onset are interrelated factors influencing autoimmunity.

Does non-erosive rheumatoid arthritis exist? A cross-sectional analysis and a systematic literature review.

OBJECTIVE: To evaluate the prevalence and factors associated with non-erosive rheumatoid arthritis (RA). METHODS: First, a cross-sectional analytical study was performed. Non-erosive disease, defined as the absence of any erosion on X-rays after 5 years of RA, was evaluated in 500 patients. Further and additional evaluations including ultrasonography (US) and computed tomography (CT) were performed in those patients meeting the eligibility criteria. The Spearman correlation coefficient, kappa analysis, and Kendall׳s W test were used to analyze the data. Second, a systematic literature review (SLR) was performed following the PRISMA guidelines. RESULTS: Of a total of 40 patients meeting the eligibility criteria for non-erosive RA, eight patients were confirmed to have non-erosive RA by the three methods. A positive correlation between non-erosive RA and shorter disease duration, antinuclear antibodies positivity, lower rheumatoid factor (RF) and C-reactive protein titers, lower global visual analog scale values, toxic exposures, and lower disease activity-(RAPID3) was found. In addition, an inverse correlation with anticyclic citrullinated peptide antibodies (ACPA) positivity and medication use was observed. From the SLR, it was corroborated that factors associated with this subphenotype were shorter disease duration, younger disease onset, negative ACPA and RF titers, low cytokine levels, and some genetic markers. CONCLUSION: Non-erosive RA is rare, occurring in less than 2% of cases. These findings improve on the understanding of RA patients who present without erosions and are likely to have less severe disease.