Immune reconstitution in rheumatic disease patients after autologous hematopoietic stem cell transplantation.

High-dose conditioning chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HSCT) in systemic sclerosis (SSc), lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), or rheumatoid arthritis (RA) was shown to allow eradication of the abnormal autoimmune compartment and "resetting" of the immune response, all contributing to the observed clinical response. A subset of patients has less favorable clinical outcomes after transplant, as auto-reactive memory cells may escape depletion or the regulatory immune network renewal be incomplete. Conditioning permits non-specific abrogation of the autoreactive T- and B-cell responses and eliminates the autoimmune repertoire. Re-infusion of autologous hematopoietic stem cells shortens the leucopenia duration and contributes to both hematologic and immune reconstitutions. After engraftment and neutrophil recovery, the first phase of immune reconstitution is characterized by clonal expansion of residual memory lymphocytes in response to early antigen stimulation and/or lymphopenia-induced proliferation. Renewal of the immune repertoire follows through exportation of de novo generated thymic-derived naïve T cells and bone marrow-derived naïve B cells, expansion of the regulatory network, and a shift from a pro-inflammatory to a more auto-tolerant profile. We review the well-described mechanisms of immune resetting and their relative contribution to disease control according to the transplantation regimen and the underlying rheumatic diseases.

Percepção de cirurgiões-dentistas acerca de manifestações orais de doenças imunomediadas e autoimunes / Perception of dentists about oral manifestations of immune-mediated and autoimmune diseases / Percepción de los odontólogos sobre las manifestaciones bucales de las enfermedades inmunomediadas y autoinmunes

Objetivo: Avaliar o nível de conhecimento dos Cirurgiões-Dentistas sobre as manifestações orais de doenças autoimunes. Metodologia: Trata-se de um estudo analítico, observacional e transversal do tipo inquérito. O universo foi composto por Cirurgiões-Dentistas devidamente cadastrados nos Conselhos Regionais de Odontologia (CRO) do Brasil, atuantes tanto em instituições ou consultórios privados quanto em instituições públicas. A amostra foi constituída por conveniência e a participação dos Cirurgiões-Dentistas foi realizada através de formulários digitais que foram enviados aos e-mails e redes sociais dos profissionais. Ao todo 111 Cirurgiões-Dentistas participaram da pesquisa. Resultados: Do total de indivíduos que constituíram a amostra, 45,9% foi do gênero feminino e 54,1% do gênero masculino, com idades entre 22-46 anos, média de 29,57 ± 6,10. Quando avaliada a média percentual de acertos dos participantes da pesquisa, a amostra de Cirurgiões-Dentistas demonstrou um moderado conhecimento acerca das manifestações orais de doenças imunologicamente media[1]das e autoimunes (M=63,6%; DM= 23,4; DP= 29,1). Conclusão: Os Cirurgiões-Dentistas ainda demonstram uma carência considerável de conhecimento acerca de doenças imunomediadas e autoimunes, dificultando a realização de diagnósticos precoces e tratamentos adequados. A maioria dos Cirurgiões-Dentistas demonstra desconhecer completamente qual terapêutica deve ser adotada corretamente para cada caso... (AU)

Objective: To assess the level of knowledge of dentists about the oral manifestations of autoimmune diseases. Methodology: This is an analytical, observational and cross-sectional study of the survey type. The universe was composed of Dental Surgeons duly registered in the Regional Councils of Dentistry (CRO) in Brazil, working both in institutions or private offices and in public institutions. The sample was constituted for convenience and the participation of the Dental Surgeons was carried out through digital forms that were sent to the professionals' e-mails and social networks. A total of 111 Dental Surgeons participated in the survey. Results: Of the total number of individuals who constituted the sample, 45.9% were female and 54.1% were male, aged between 22-46 years, mean of 29.57 ± 6.10. When the average percentage of correct answers of the research participants was evaluated, the sample of Dental Surgeons demon[1]strated a moderate knowledge about the oral manifestations of immunologically mediated and autoimmune diseases (M=63.6%; DM= 23.4; SD= 29, 1). Conclusion: Dental surgeons still demonstrate a considerable lack of knowledge about immune-mediated and autoimmune diseases, making it difficult to carry out early diagnoses and adequate treatments. Most dentists are completely unaware of which therapy should be correctly adopted for each case... (AU)

Objetivo: Evaluar el nivel de conocimiento de los odontólogos sobre las manifestaciones bucales de las enfermedades autoinmunes. Metodología: Se trata de un estudio analítico, observacional y transversal del tipo encuesta. El universo estuvo compuesto por Cirujanos Dentistas debidamente registrados en los Consejos Regionales de Odontología (CRO) de Brasil, actuando tanto en instituciones o consultorios privados como en instituciones públicas. La muestra se constituyó por conveniencia y la participación de los Cirujanos Dentistas se realizó a través de formularios digitales que fueron enviados a los correos electrónicos y redes sociales de los profesionales. Un total de 111 Cirujanos Dentales participaron en la encuesta. Resultados: Del total de individuos que constituyeron la muestra, el 45,9% eran del sexo femenino y el 54,1% del sexo masculino, con edades entre 22-46 años, media de 29,57 ± 6,10. Cuando se evaluó el porcentaje promedio de respuestas correctas de los participantes de la investigación, la muestra de Cirujanos Dentistas demostró un conocimiento moderado sobre las manifestaciones orales de las enfermedades inmunológicas y autoinmunes (M=63,6%; DM= 23,4; DE= 29,1). Conclusión: Los cirujanos dentistas aún demuestran un desconocimiento considerable sobre las enfermedades inmunomediadas y autoinmunes, lo que dificulta la realización de diagnósticos tempranos y tratamientos adecuados. La mayoría de los odontólogos desconocen por completo qué terapia se debe adoptar correctamente para cada caso... (AU)

Oral Lesions of Immune-Mediated and Autoimmune Diseases: A 12-year Experience at a Single Brazilian Referral Center.

BACKGROUND: Oral lesions of immune-mediated and autoimmune diseases have been well-documented, but studies from Brazil are limited. The varied spectrum of oral lesions within this demographic group poses challenges to clinicians, particularly when they occur in isolation. This study aimed to evaluate the occurrence, clinical characteristics, and management of patients with oral lesions of immune-mediated and autoimmune diseases at a single center in Brazil. METHODS: A retrospective cross-sectional study was conducted from 2010 to 2022. Clinicodemographic data, histopathological features, and treatment modalities were analyzed descriptively and analytically. RESULTS: Of the 3,790 oral and maxillofacial lesions diagnosed, 160 (4.2%) were confirmed as immune-mediated or autoimmune diseases. The population surveyed predominantly consisted of women (73.7%), with a mean age of 60.2 years. Oral lichen planus (51.3%), mucous membrane pemphigoid (MMP) (23.7%), and pemphigus vulgaris (PV) (19.4%) were the most prevalent lesions. The buccal mucosa (59.4%) was predominantly affected, with pain reported in 46.2% of cases, notably in individuals with PV and MMP. The average time to disease stabilization post-local and/or systemic corticosteroid therapy was 15.8 months for systemic lupus erythematosus, 8.7 months for MMP, and 6.5 months for PV. CONCLUSION: Although oral lesions related to immune-mediated and autoimmune diseases are uncommon, their diverse clinicopathological aspects require multidisciplinary management.

Association of systemic lupus erythematosus standard of care immunosuppressants with glucocorticoid use and disease outcomes: a multicentre cohort study.

BACKGROUND: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data. METHODS: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes. RESULTS: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual. CONCLUSIONS: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus.

Addressing the unspoken: sexual dysfunction in men with systemic lupus erythematosus, a call to action for rheumatologists.

INTRODUCTION: Sexual dysfunction (SD) is highly prevalent and multifactorial; nevertheless, recent research has shed light on a notable phenomenon: male patients with systemic lupus erythematosus (SLE) exhibit an elevated prevalence of sexual function disorders compared with the general population. Despite this recognition, the precise nature and extent of this association remain incompletely understood. OBJECTIVES: This comprehensive review aims to clarify the link by providing an overview of the fundamental components of normal male sexual function, delving into the pathogenesis of male SD and exploring the primary factors predisposing male SLE patients to SD. Additionally, the review offers insights into potential screening, diagnostic, and treatment strategies based on the current body of literature. METHODS: A meticulous search of relevant literature was conducted using the PubMed and Google Scholar databases. RESULTS: Studies exploring the correlation between SLE and SD in both genders have revealed a nearly 2-fold increased risk of SD among individuals with SLE compared with healthy counterparts. Moreover, these studies suggest that male SLE patients may have a higher susceptibility to SD, with reported prevalence ranging from 12% to 68%, compared with 0% to 22% in healthy individuals. Male patients with SLE are influenced by a spectrum of pathological factors, including pharmacological, psychological, and disease-related determinants, which, through their intricate interplay, elevate the likelihood of developing SD. CONCLUSION: Healthcare professionals must remain vigilant in understanding the intricacies of human sexuality and its dysfunction, particularly in males with SLE. The objective is to establish effective and potentially standardized methods for promptly diagnosing and optimally managing SD, recognizing its significant impact on the quality of life for males living with SLE. The pivotal role of rheumatologists in initiating discussions about sexual health, diagnosing SD, investigating causes, and implementing tailored strategies is underscored as crucial in addressing this multifaceted issue.

Position statement of the Brazilian society of Rheumatology on mesna use as a preventive therapy for bladder disease in patients with systemic autoimmune diseases and systemic vasculitis under cyclophosphamide treatment.

OBJECTIVE: To review current literature to support the use of mesna as a preventive therapy for hemorrhagic cystitis and bladder cancer in patients with systemic autoimmune diseases and systemic vasculitis treated with cyclophosphamide. MATERIALS AND METHODS: The search for articles was conducted systematically through MEDLINE, LILACS, Cochrane Library, and Embase databases. Only articles in English were selected. For available records, titles and abstracts were selected independently by two investigators. RESULTS: Eighteen studies were selected for analysis. The known adverse effects of cyclophosphamide were hematological toxicity, infections, gonadal toxicity, teratogenicity, increased risk for malignancy and hemorrhagic cystitis. Long-term toxicity was highly dependent on cyclophosphamide cumulative dose. The risk of bladder cancer is especially higher in long-term exposure and with cumulative doses above 36 g. The risk remains high for years after drug discontinuation. Hemorrhagic cystitis is highly correlated with cumulative dose and its incidence ranges between 12 and 41%, but it seems to be lower with new regimens with reduced cyclophosphamide dose. No randomized controlled trials were found to analyze the use of mesna in systemic autoimmune rheumatic diseases and systemic vasculitis. Retrospective studies yielded conflicting results. Uncontrolled prospective studies with positive results were considered at high risk of bias. No evidence was found to support the use of mesna during the treatment with cyclophosphamide for autoimmune diseases or systemic vasculitis to prevent hemorrhagic cystitis and bladder cancer. In the scenarios of high cumulative cyclophosphamide dose (i.e., > 30 g), patients with restricted fluid intake, neurogenic bladder, therapy with oral anticoagulants, and chronic kidney disease, mesna could be considered. CONCLUSION: The current evidence was found to be insufficient to support the routine use of mesna for the prophylaxis of hemorrhagic cystitis and bladder cancer in patients being treated for systemic autoimmune diseases and systemic vasculitis with cyclophosphamide. The use may be considered for selected cases.

Biological changes in human B-cell line Ramos (RA.1) related to increasing doses of human parathyroid hormone.

Background: The etiopathogenesis of autoimmune diseases is multifactorial, including hormonal factors. Remission of autoimmunity has been observed following treatment for concomitant hyperparathyroidism. Additionally, patients with autoimmune diseases have shown increased expression of parathyroid hormone receptor (PTH1R) and altered distribution of B cells subsets. Hence, this study aims to evaluate potential mechanisms and in vitro effects of PTH stimulation on B lymphocytes. Methods: Using the human B-cell line Ramos (RA.1), various biological effects were evaluated with and without parathyroid hormone (PTH) stimulation at varying concentrations. Flow cytometry was employed to evaluate the phenotype of B lymphocytes based on IgD and CD38 expression, apoptosis induction via Annexin V and proliferation using CFSE. IgM production was quantified through ELISA, and Western blot analysis was performed to assess syk protein phosphorylation as an indicator of cell activation. Results: Ramos cells (RA.1) evidenced a statistically significant change in the phenotype under human PTH stimulation, demonstrating an increased proportion of germinal centre cells (Bm3-Bm4) when stimulated with high concentrations of PTH. Conclusions: The in vitro effects of PTH in B cells subsets align with previous findings of an altered phenotype in B lymphocytes expressing PTH1R among autoimmune disease patients, suggesting a potential role of this hormone in the pathophysiology of autoimmune diseases. However, further studies are necessary to elucidate the mechanisms by which PTH generates observed effects in B lymphocytes and to determine if PTH plays a role in autoimmunity.

The impact of genetic variants related to vitamin D and autoimmunity: A systematic review.

Over the past few years, there has been a notable increment in scientific literature aimed at unraveling the genetic foundations of vitamin D signaling and its implications for susceptibility to autoimmunity, however, most of them address isolated diseases. Here, we conducted a systematic review of genetic variants related to vitamin D and autoimmune diseases and we discussed the current landscape of susceptibility and outcomes. Of 65 studies analyzed, most variants cited are in vitamin D binding protein (VDBP; rs2282679 GC gene), 25-hydroxylase (rs10751657 CYP2R1), 1α-hydroxylase (rs10877012, CYP27B1) and the nuclear hormone receptor superfamily [FokI (rs2228570), BsmI (rs1544410), ApaI (rs7975232), and TaqI (rs731236) in VDR gene]. Therefore, our findings confirmed the associations of several genetic variants of vitamin D signaling with a broad spectrum of autoimmune diseases/traits. In addition, given the low number of papers found with functional analysis, further studies to elucidate the real effect that the variants exert on Vitamin D signaling are recommended.

Diagnostic tests for progestogen hypersensitivity.

Progesterone is an endogenous hormone, produced by the adrenal cortex, the gonads and in women, its source is the corpus luteum. Progesterone is produced in the late phase of the menstrual cycle, when implantation of the zygote does not occur, the corpus luteum involutes and the release of progesterone is suppressed, thus initiating menstruation. Progestogen Hypersensitivity were initially identified as hormone allergy and were related to endogenous reactions to hormones and alteration of ovarian function. Skin manifestations such as dermatitis or urticaria were initially reported and described as progesterone autoimmune dermatitis, although the immune-mediated mechanism was not clear. Currently there is no standardization for in vivo or in vitro tests for Progestogen Hypersensitivity diagnosis. In this review, we will address the different diagnostic methods of this disease.

[Molecular mimicry between human thyroid peroxidase, thyroglobulin, cosinophil peroxidase, IL-24 and microorganisms antigens]. / Mimetismo molecular entre peroxidasa tiroidea humana, tiroglobulina, peroxidasa de eosinófilos, IL-24 y antígenos de microorganismos.

OBJECTIVE: Identify molecular mimicry between TPO, eosinophil peroxidase (EPX), thyroglobulin and IL24 and microorganism antigens. METHODS: Through in silico analysis, we performed local alignments between human and microorganism antigens with PSI-BLAST. Proteins that did not present a 3D structure were modeled by homology through the Swiss Modeller server and epitope prediction was performed through Ellipro. Epitopes were located in the 3D models using PYMOL software. RESULTS: A total of 38 microorganism antigens (parasites, bacteria) had identities between 30% and 45%, being the highest with Anisakis simplex. The alignment between 2 candidate proteins from A. simplex and EPX presented significant values, with identities of 43 and 44%. In bacteria, Campylobacter jejuni presented the highest identity with thyroglobulin (35%). 220 linear and conformational epitopes of microorganism antigens were predicted. Peroxidasin-like proteins from Toxocara canis and Trichinella pseudospiralis presented 10 epitopes similar to TPO and EPX, as possible molecules triggering cross-reactivity. No virus presented identity with the human proteins studied. CONCLUSION: TPO and EPX antigens shared potential cross-reactive epitopes with bacterial and nematode proteins, suggesting that molecular mimicry could be a mechanism that explains the relationship between infections and urticaria/hypothyroidism. In vitro work is needed to demonstrate the results obtained in the in silico analysis.

OBJETIVO: Identificar mimetismo molecular entre TPO, eosinofil peroxidasa (EPX), tiroglobulina e IL24 y antígenos de microorganismos. MÉTODOS: A través de análisis in silico, realizamos los alineamientos locales entre los antígenos humanos y de microorganismos con PSI-BLAST. Las proteínas que no presentaban estructura 3D, fueron modeladas por homología a través del servidor Swiss Modeller y se realizó una predicción de epítopes a través de Ellipro. Los epítopes se localizaron en los modelos 3D utilizando el software PYMOL. RESULTADOS: Un total de 38 antígenos de microorganismos (parásitos y bacterias), tuvieron identidades entre 30 y 45%, siendo los más altos con Anisakis simplex. El alineamiento entre dos proteínas candidatas de A. simplex y EPX presentaron valores importantes, con identidades de 43 y 44%. En las bacterias, Campylobacter jejuni presentó la mayor identidad con tiroglobulina (35%). Se predijeron 220 epítopes lineales y conformacionales de antígenos de microorganismos. Las proteínas similares a la peroxidasina de Toxocara canis y Trichinella pseudospiralis presentaron diez epítopes similares a TPO y EPX, como posibles moléculas desencadenantes de una reactividad cruzada. Ningún virus presentó identidad con las proteínas humanas estudiadas. CONCLUSIÓN: Los antígenos TPO y EPX compartieron potenciales epítopes de reacción cruzada con proteínas bacterianas y nematodos, lo que sugiere que el mimetismo molecular podría ser un mecanismo que explique la relación entre infecciones y la urticaria/hipotiroidismo. Se necesitan trabajos in vitro que demuestren los resultados obtenidos en el análisis in silico.

[Molecular mimic between cardiovascular diseases and microorganism antigens]. / Mimetismo molecular entre enfermedades cardiovasculares y antígenos de microorganismos.

INTRODUCTION: Cardiovascular diseases are the result of genetic and environmental interaction that conditions the integrity of the heart and blood vessels. Risk factors include infections. The inflammatory response against the infectious agent is a trigger of autoimmune cardiovascular diseases due to the similarity between the pathogen proteins and human antigens, since the immune response can present cross-reactivity caused by molecular mimicry. METHODS: We performed a search for pathogens involved in autoimmune heart diseases and autoantigens 9 associated with these diseases in the Pubmed and Google Scholar search engines. Identity between proteins was performed through global alignments using PSI-BLAST. The 3D structures of the proteins were obtained by Uniprot or NCBI and, if not found, the structure was modeled by homology using the Swiss Model server. Epitope prediction was performed through Ellipro and the Immunological Epitope Database (IEDB). In addition, the PYMOL program was used to visualize proteins in 3D and position the epitopes in the structure. RESULTS: A total of ten cardiovascular proteins showed identity (30-88,24%) in their amino acid sequences with antigens from 10 pathogens. Actin proteins and heat shock protein (HSP) families had higher levels of identity with Trypanosoma Cruzi, Cryptococcus neoformans, and Chlamydia trachomatis, 71,47%, 88,24%, and 80,61%, respectively. Other pathogens, such as Streptococcus pyogenes, Bacillus sp, Magnetospirillum gryphiswaldense, Helicobacter pylori and Chlamydia pneumoniae, presented a moderate identity with a maximum value of 65,79%. CONCLUSION: Human actin and HSPs share a high degree of conservation with epitopes from various microorganisms, such as bacteria, fungi and protozoa, suggesting molecular mimicry and cross-reactivity as a mechanism for the development of atherosclerosis, heart disease rheumatic disease, myocarditis and Chagas heart disease. In vitro and in vivo work is needed to demonstrate the results obtained in the In Silico analysis.

INTRODUCCIÓN: Las enfermedades cardiovasculares son el resultado de la interacción genética y ambiental que condiciona la integridad del corazón y los vasos sanguíneos. Los factores de riesgo incluyen infecciones. La respuesta inflamatoria contra el agente infeccioso es un desencadenante de las enfermedades cardiovasculares autoinmunes, debido a la similitud entre las proteínas del patógeno y los antígenos humanos, pues la respuesta inmunitaria puede presentar reactividad cruzada causada por mimetismo molecular. MÉTODOS: Realizamos una búsqueda de patógenos involucrados en enfermedades cardíacas autoinmunes y de autoantígenos asociados a estas enfermedades en los buscadores Pubmed y Google Scholar. La identidad entre proteínas se realizó a través de alineamientos globales utilizando PSI-BLAST. Las estructuras 3D de las proteínas fue obtenida por Uniprot o NCBI y, si no se encontraban, las estructuras se modelaban por homología, utilizando el servidor Swiss Model. La predicción de los epítopes se realizó a través de Ellipro, y la Base de Datos de Epítopos Inmunológicos (IEDB). Además, se utilizó el programa PYMOL para la visualización de proteínas en 3D, y el posicionamiento de los epítopes en la estructura. RESULTADOS: Diez proteínas cardiovasculares mostraron una identidad (30-88,24%) en sus secuencias de aminoácidos con antígenos de diez patógenos. Las proteínas de actina y las familias de proteínas de choque térmico (HSP, por sus siglas en inglés), presentaron niveles de identidad más altos con Trypanosoma Cruzi, Cryptococcus neoformans y Chlamydia trachomatis, 71,47%, 88,24% y 80,61%, respectivamente. Otros patógenos, como Streptococcus pyogenes, Bacillus sp, Magnetospirillum gryphiswaldense, Helicobacter pylori y Chlamydia pneumoniae, presentaron identidad moderada con un valor máximo del 65,79%. CONCLUSIÓN: La actina humana y las HSP comparten un alto grado de conservación con epítopos de varios microorganismos, como bacterias, hongos y protozoos; lo que sugiere la imitación molecular y la reactividad cruzada como mecanismos para el desarrollo de la aterosclerosis, la enfermedad cardíaca reumática, la miocarditis y la enfermedad cardíaca de Chagas. Se necesitan trabajos in vitro e in vivo, que demuestren los resultados obtenidos en el análisis In Silico.

Eye and lid involvement as an uncommon feature of pemphigus foliaceus in a pediatric patient.

Pemphigus foliaceus (PF) is an autoimmune blistering disorder which affects the superficial layers of the epidermis with rare mucosal involvement. We present the case of a 12-year-old girl with PF involving the eyes and eyelids. A literature review of pediatric nonendemic PF revealed another two cases with ocular manifestations. Eyelid involvement is an uncommon feature of PF that should be properly identified and treated.

Characteristics and risk factors of COVID-19 breakthrough infections in Idiopathic Inflammatory Myopathies: Results from the COVAD study.

OBJECTIVES: To explore prevalence, characteristics and risk factors of COVID-19 breakthrough infections (BIs) in idiopathic inflammatory myopathies (IIM) using data from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. METHODS: A validated patient self-reporting e-survey was circulated by the COVAD study group to collect data on COVID-19 infection and vaccination in 2022. BIs were defined as COVID-19 occurring ≥14 days after 2 vaccine doses. We compared BIs characteristics and severity among IIMs, other autoimmune rheumatic and non-rheumatic diseases (AIRD, nrAID), and healthy controls (HC). Multivariable Cox regression models assessed the risk factors for BI, severe BI and hospitalisations among IIMs. RESULTS: Among 9449 included response, BIs occurred in 1447 (15.3%) respondents, median age 44 years (IQR 21), 77.4% female, and 182 BIs (12.9%) occurred among 1406 IIMs. Multivariable Cox regression among IIMs showed age as a protective factor for BIs [Hazard Ratio (HR)=0.98, 95%CI = 0.97-0.99], hydroxychloroquine and sulfasalazine use were risk factors (HR = 1.81, 95%CI = 1.24-2.64, and HR = 3.79, 95%CI = 1.69-8.42, respectively). Glucocorticoid use was a risk factor for severe BI (HR = 3.61, 95%CI = 1.09-11.8). Non-White ethnicity (HR = 2.61, 95%CI = 1.03-6.59) was a risk factor for hospitalisation. Compared with other groups, patients with IIMs required more supplemental oxygen therapy (IIM = 6.0% vs AIRD = 1.8%, nrAID = 2.2%, and HC = 0.9%), intensive care unit admission (IIM = 2.2% vs AIRD = 0.6%, nrAID, and HC = 0%), advanced treatment with antiviral or monoclonal antibodies (IIM = 34.1% vs AIRD = 25.8%, nrAID = 14.6%, and HC = 12.8%), and had more hospitalisation (IIM = 7.7% vs AIRD = 4.6%, nrAID = 1.1%, and HC = 1.5%). CONCLUSION: Patients with IIMs are susceptible to severe COVID-19 BI. Age and immunosuppressive treatments were related to the risk of BIs.

Autoimmunity in centenarians. A paradox.

Autoimmune diseases (ADs) are one of the groups of chronic illnesses that impose a significant burden of disease and health costs worldwide. Age is a crucial risk factor for the onset of ADs. Theoretically, it is inferred that with organic and immune system aging, the loss of immune tolerance and specificity of immune activity becomes more intense, the probability of autoimmunity is increasing. However, there is a group of individuals whose prevalence of ADs is very low or non-existent, despite the biological aging. This paradox in autoimmunity raises questions. Centenarians, individuals who are over 100 years old, are possibly the most successful model of biological aging in humans. Most of these individuals exhibit a favorable health phenotype. To date, primary data evidence and potential hypotheses explaining this phenomenon are lacking globally, even though this paradox could provide valuable, original, and relevant information regarding the understanding of risk or protective factors, biological drivers, and biomarkers related to autoimmunity. Herein we discuss some hypothesis that may explain the absence of ADs in centenarians, including inflammaging, immunosenescence and immune resilience, immune system hyperstimulation, proteodynamics, and genetics.

Intervención nutricional orientada al control del proceso inflamatorio en pacientes con espondilitis enteropática

Introducción: La espondilitis enteropática es una enfermedad inflamatoria, sistémica y crónica que se caracteriza por afectar el aparato digestivo y el sistema osteomioarticular; el proceso inflamatorio genera manifestaciones clínicas que afectan la capacidad funcional y la percepción de calidad de vida de los pacientes. Objetivo: Evaluar los resultados de una intervención nutricional orientada al control del proceso inflamatorio en pacientes con espondilitis enteropática. Métodos: Se realizó una investigación observacional y descriptiva longitudinal que incluyó como universo a 19 pacientes con diagnóstico confirmado de espondilitis enteropática atendidos en el Hospital Andino de Chimborazo en el periodo comprendido entre julio 2022 y julio 2023. La muestra quedó conformada por 17 pacientes. Se aplicó una intervención nutricional durante 10 meses que incluyó como elemento central la suplementación con alimentos ricos en probióticos según esquema definido por especialista en nutrición clínica. Resultados: Promedio de edad de 43,51 años, predominio del sexo femenino (64,70 %) y del tiempo de evolución de la enfermedad entre 5 y 10 años (58,82 %). Todos los marcadores de inflamación medidos durante el estudio mejoraron durante el seguimiento realizado a los pacientes; a los 9 meses se identificó aumento del porcentaje de pacientes con proteína C reactiva negativa y fibrinógeno y velocidad de sedimentación globular normal. Conclusiones: La intervención nutricional aplicada contribuye a mejorar los valores séricos de los marcadores de inflamación en los pacientes con diagnóstico de espondilitis enteropática.

Introduction: Enteropathic spondylitis is an inflammatory, systemic and chronic disease that is characterized by affecting the digestive system and the osteomyoarticular system; The inflammatory process generates clinical manifestations that affect the functional capacity and perception of quality of life of patients. Objective: To evaluate the results of a nutritional intervention aimed at controlling the inflammatory process in patients with enteropathic spondylitis. Methods: A longitudinal observational and descriptive investigation was carried out that included as a universe 19 patients with a confirmed diagnosis of enteropathic spondylitis treated at the Andino Hospital of Chimborazo in the period between July 2022 and July 2023. The sample was made up of 17 patients. A nutritional intervention was applied for 10 months that included as a central element supplementation with foods rich in probiotics according to a scheme defined by a clinical nutrition specialist. Results: Average age of 43.51 years, predominance of the female sex (64.70%) and duration of the disease between 5 and 10 years (58.82%). All inflammation markers measured during the study improved during the patients' follow-up; At 9 months, an increase in the percentage of patients with negative C-reactive protein and fibrinogen and normal erythrocyte sedimentation rate was identified. Conclusions: The applied nutritional intervention contributed to improving serum values ​​of inflammation markers in patients diagnosed with enteropathic spondylitis.

Nutritional interventions as modulators of the disease activity for idiopathic inflammatory myopathies: a scoping review.

Idiopathic inflammatory myopathies (IIMs) are chronic, autoimmune connective tissue diseases associated with significant morbidity and disability. Nutrients can activate the immune system and contribute to chronic low-grade inflammation (LGI). Chronic muscle inflammation leads to imbalanced pro-inflammatory and anti-inflammatory cytokines, causing inadequate nutrition, weight loss and muscle weakness during a negative cycle. Owing to its potential to modulate LGI in various diseases, the Mediterranean diet (Med Diet) has been extensively studied. This scoping review explores the nutritional implications and recommendations of the Med Diet as a treatment for immune-mediated diseases, focusing on the gaps in IIM nutritional interventions. A comprehensive literature search of the MEDLINE and EBSCO databases between September 2018 and December 2022 was performed. We identified that the Med Diet and its specific components, such as omega-3 (nω3) fatty acids, vitamin D and antioxidants, play a role in the dietary treatment of connective tissue-related autoimmune diseases. Nutritional interventions have demonstrated potential for modulating disease activity and warrant further exploration of IIMs through experimental studies. This review introduces a dietary therapeutic approach using the Med Diet and related compounds to regulate chronic inflammatory processes in IIMs. However, further clinical studies are required to evaluate the efficacy of the Med Diet in patients with IIMs. Emphasising a clinical-nutritional approach, this study encourages future research on the anti-inflammatory effects of the Med Diet on IIMs. This review highlights potential insights for managing and treating these conditions using a holistic approach.

Clinical and Sociodemographic Features of Alopecia Areata in Five Colombian Cities: An Analysis of the RENAAC Registry.

BACKGROUND: Alopecia areata (AA) is an autoimmune disease characterized by non-scaring hair loss and preservation of hair follicles. The information available on disease course, and clinical features of AA is scarce worldwide, and almost nonexistent in Colombia. OBJECTIVE: To determine the clinical and sociodemographic characteristics of patients diagnosed with AA who presented to a dermatology consultation in five Colombian cities. MATERIAL AND METHODS: This was a retrospective and multicenter study on data from an ongoing National Registry of Alopecia Areata in Colombia (RENAAC) collected in Bogota, Cali, Cartagena, Barranquilla, and Medellin, Colombia from March 2022 through April 2023. Data was recorded in a standardized form by trained physicians. The variables were expressed as measures of central tendency and dispersion, and absolute and relative frequencies. RESULTS: A total of 562 patients were included, 59.4% of whom were women, aged between 15 and 49 years (63.9%) with a mean disease course of 1.7 years. The most common finding was multiple plaque (53.2%), the predominant AA subtype was patchy (71.4%), and 29.5% of the patients had a past dermatological history, 18.3% had a past endocrinological history, and 8.9% had a past psychiatric history. The treatments most widely used were steroid injections (76.4%), 5% topical minoxidil (46.4%), followed by high-potency corticosteroids (42.5%). STUDY LIMITATIONS AND CONCLUSIONS: AA was slightly predominant in women. As seen in other populations, this disease had an earlier onset in men vs women. Presentation in pediatric age was uncommon. The previous history of other dermatological diseases was checked in almost one third of the patients. Analysis of the co-presentation of AA with other autoimmune diseases is biased due to excluding patients with systemic erythematous lupus from the study.

Espondiloencondrodisplasia con desregulación inmune relacionada a ACP5. Reporte de cuatro casos / Spondyloenchondrodysplasia with immune dysregulation related to ACP5. A report of 4 cases

La espondiloencondrodisplasia con desregulación inmune relacionada a ACP5 (SPENCDI #607944, por la sigla de spondyloenchondrodysplasia with immune dysregulation y el número que le corresponde en OMIM, Online Mendelian Inheritance in Man) es una displasia inmuno-ósea poco frecuente con manifestaciones heterogéneas y gravedad variable. Presenta lesiones espondilometafisarias, disfunción inmune y compromiso neurológico. Se reportan aspectos clínicos, radiológicos y genéticos de cuatro niñas con SPENCDI en un hospital pediátrico. Todas presentaron manifestaciones esqueléticas y tres de ellas enfermedad inmunológica grave. Se encontró en tres pacientes la variante probablemente patogénica c.791T>A; p.Met264Lys en homocigosis, y en una paciente las variantes c.791T>A; p.Met264Lys y c.632T>C; p.lle211Thr (variante de significado incierto con predicción patogénica según algoritmos bioinformáticos) en heterocigosis compuesta en ACP5. La presencia de la variante repetida c.791T>A sugiere la posibilidad de un ancestro en común en nuestra población. El reconocimiento y diagnóstico de esta entidad es importante para lograr un oportuno abordaje, que deberá ser multidisciplinario, orientado hacia la prevención de posibles complicaciones.

Spondyloenchondrodysplasia with immune dysregulation related to ACP5 (SPENCDI, OMIM number 607944) is an uncommon immune-skeletal dysplasia with heterogeneous manifestations and variable severity. It is characterized by spondylar and metaphyseal lesions, immune dysfunction, and neurological involvement. Here we report the clinical, radiological and genetic aspects of 4 girls with SPENCDI treated at a children's hospital. They all had skeletal manifestations and 3 developed severe immune disease. In 3 patients, the likely pathogenic variant c.791T>A; p.Met264Lys (homozygous mutation) was observed, while 1 patient had variants c.791T>A; p.Met264Lys and c.632T>C; p.lle211Thr (variant of uncertain significance with pathogenic prediction based on bioinformatics algorithms) caused by a compound heterozygous mutation in ACP5. The repeated presence of variant c.791T>A suggests the possibility of a common ancestor in our population. The recognition and diagnosis of this disorder is important to achieve a timely approach, which should be multidisciplinary and aimed at preventing possible complications.

Ocular cicatricial pemphigoid: is there an association with autoimmune diseases?

PURPOSE: To assess the prevalence of autoimmune diseases (ADs) associated with ocular cicatricial pemphigoid (OCP) and analyze clinical, laboratory, and treatment associations between these entities. METHODS: A multicentre cross-sectional study of patients with an OCP diagnosis. The population was divided into two groups according to their association with other ADs or not. Clinical, laboratory and treatment variables were described and compared between groups. A multivariable logistic regression analysis was performed to identify variables that could suggest the association between OCP and ADs. RESULTS: Eighty-eight patients were recruited, with a mean age at diagnosis of 64.3 years (SD 11.9). Biopsy was performed in 86.8% of the patients. There was a median delay of 2 years from the onset of symptoms to diagnosis. Extraocular involvement was evidenced in 11.5%. The group associated with ADs included 24 patients (27.3%). The most prevalent diagnosis was Sjögren´s syndrome. Hypergammaglobulinemia was associated with ADs and OCP, adjusted for age, sex, smoking, skin and mucosal involvement, and erythrocyte sedimentation rate (OR 8.7; 95%CI 1.6-46.8; p = 0.012). CONCLUSIONS: Due to OCP's autoimmune nature, it could coexist with other ADs. This study observed that more than a quarter of the population presented with this association, and hypergammaglobulinemia could suggest it.