Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease

ObjectiveThe relationship between autoimmune diseases and the gut microbiome has been intensively studied, and several autoimmunity-associated bacterial taxa have been identified. However, much less is known about the roles of the gut virome in autoimmune diseases.MethodsHere, we performed a whole gut virome analysis based on the shotgun sequencing of 476 Japanese which included patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis and healthy control subjects.ResultsOur case–control comparison of the viral abundance revealed that crAss-like phages, which are one of the main components of a healthy gut virome, significantly decreased in the gut of the patients with autoimmune disease, specifically the patients with RA and SLE. In addition, Podoviridae significantly decreased in the gut of the patients with SLE. To understand how these viruses affected the bacteriome, we performed a quantitative virus–bacterium association analysis and clustered regularly interspaced short palindromic repeat-based virus–bacterium interaction analysis. We identified a symbiosis between Podoviridae and Faecalibacterium. In addition, multiple bacterial targets of crAss-like phages were identified (eg, Ruminococcus spp).ConclusionOur data suggest that the gut virome can affect our body either directly or via bacteria. Our analyses have elucidated a previously missing part of the autoimmunity-associated gut microbiome and presented new candidates that contribute to the development of autoimmune diseases.

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Clinical Manifestations and Mechanisms of Autoimmune Disease-Related Multiple Cerebral Infarcts

Cell Transplantation ◽

10.1177/0963689719846838 ◽

2019 ◽

Vol 28 (8) ◽

pp. 1045-1052

Author(s):

Li-Li Sun ◽

Wen-Xiong Tang ◽

Min Tian ◽

Lu Zhang ◽

Zun-Jing Liu

Keyword(s):

Autoimmune Disease ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Transcranial Doppler ◽

Clinical Manifestations ◽

Cerebral Infarcts ◽

Acute Infarction ◽

Multiple Stroke ◽

Underlying Mechanisms ◽

Embolic Signals

It is important to investigate the clinical characteristics and identify the stroke mechanisms of patients with autoimmune disease-related stroke, which are necessary for early etiology diagnosis, accurate treatment and preventive strategies. In this article we retrospectively studied eight cases of acute ischemic stroke associated with autoimmune diseases, and without competing conventional stroke etiologies. The characteristics of stroke (clinical and radiological features), the laboratory tests especially serum D-dimer levels (as a marker of hypercoagulable state), and embolic signals on transcranial Doppler were evaluated for all eight patients. High-resolution magnetic resonance imaging (HRMRI), which can help to evaluate vasculitis was performed in four patients. The possible underlying mechanisms of these cases were discussed based on these manifestations. As a result, autoimmune diseases in our study included systemic lupus erythematosus ( n=5), mixed connective tissue disease ( n=1), central nervous system vasculitis ( n=1), and Takayasu arteritis ( n=1). All eight patients presented with acute infarction lesions in ≥2 vascular territories. Most patients presented with numerous small and medium infarction lesions located in the cortical and subcortical areas. Multiple stroke mechanisms were involved in these cases, including hypercoagulability ( n=4), cardiac embolism ( n=1) and vasculitis ( n=3). Embolic signals could be detected on transcranial Doppler in all three stroke mechanisms. In conclusion, our study revealed the characteristics of autoimmune disease-related stroke. For patients with multiple acute cerebral infarcts within non-single arterial territories, autoimmune disease is an important etiology not to be neglected. Multiple stroke mechanisms were involved in these cases.

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Abdominal surgery in autoimmune and autoimmune-related diseases: A review

Journal of Clinical and Investigative Surgery ◽

10.25083/2559.5555/6.2.1 ◽

2021 ◽

Vol 6 (2) ◽

pp. 76-87

Author(s):

Erdal Uysal ◽

◽

Mehmet Dokur ◽

Gokturk Maralcan

Keyword(s):

Autoimmune Disease ◽

Early Detection ◽

Abdominal Surgery ◽

Autoimmune Diseases ◽

High Mortality ◽

Indirect Effects ◽

Mortality And Morbidity ◽

Abdominal Organs ◽

The Relationship ◽

Significant Mortality

Autoimmune diseases can have a widespread effect throughout the system and can cause high mortality and morbidity, depending on their involvement in the abdominal organs and systems. Most of the abdominal organs are damaged as a result of the direct or/ and indirect effects of autoimmune diseases. Therefore, abdominal surgeries should be performed to eliminate any complications related to these effects. There could be a significant relationship between abdominal surgery and autoimmune and autoimmune-related diseases. The aim of this study was to reveal the possible relationship between autoimmune and autoimmune-related diseases that cause significant mortality and morbidity. In this way, we further aimed at increasing the awareness of clinicians on this subject, along with providing them with the related publications on autoimmune and autoimmune-related diseases and abdominal surgery. Taking all these into consideration, autoimmune and autoimmune-related diseases can also influence the abdominal organs. The influence may be directly related to the involvement of the organ and system as a result of the autoimmune disease or indirectly related to the influence of the organs and systems. Such influence leading to complications may require urgent or elective abdominal surgery, which can further cause high mortality and morbidity. Therefore, it is significant for all clinicians, especially surgeons, to be aware of the relationship between autoimmune diseases and abdominal surgery. The early detection and treatment of the complications related to the abdominal involvement of autoimmune and autoimmune-related diseases could decrease mortality and morbidity.

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Serum immunoglobulin a deficiency and autoimmune comorbidities: a crossectional study in 281 patients with systemic lupus erythematosus

Revista da Associação Médica Brasileira ◽

10.1590/1806-9282.66.6.752 ◽

2020 ◽

Vol 66 (6) ◽

pp. 752-756

Author(s):

Gustavo Felício Alexandroni Linzmeyer ◽

Fabiane Karen Miyake ◽

Thiago Alberto F. C. Gomes Dos Santos ◽

Thelma L Skare

Keyword(s):

Systemic Lupus Erythematosus ◽

Autoimmune Disease ◽

Autoimmune Diseases ◽

Clinical Data ◽

Lupus Erythematosus ◽

Immunoglobulin A ◽

Hashimoto Thyroiditis ◽

Iga Deficiency ◽

Systemic Lupus ◽

High Prevalence

SUMMARY OBJECTIVE To study the profile of associated autoimmune diseases in a series of patients with systemic lupus erythematosus (SLE) and see if such associations are linked to IgA deficiency. METHODS Two hundred eighty-one patients with SLE were studied for Ig A levels by nephelometry. Levels equal to or under 0.05g/dL were considered as IgA deficiency. Epidemiological and clinical data, including the presence of associated autoimmune diseases, were extracted from the patient’s charts. RESULTS Ig A deficiency was found in 6% of the patients. In 30.2% of SLE patients, there was at least one more autoimmune disease; Hashimoto thyroiditis and Sjögren’s syndrome were the most common. No association between the occurrence of associated autoimmune disease with IgA deficiency was found. CONCLUSIONS There is a high prevalence of autoimmune diseases associated with SLE. IgA deficiency does not affect the presence of these associations.

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Autoimmune thyroid disease and other non-endocrine autoimmune diseases

Medicinski pregled ◽

10.2298/mpns1104183t ◽

2011 ◽

Vol 64 (3-4) ◽

pp. 183-187 ◽

Cited By ~ 10

Author(s):

Ljiljana Todorovic-Djilas ◽

Tijana Icin ◽

Jovanka Novakovic-Paro ◽

Ivana Bajkin

Keyword(s):

Autoimmune Disease ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Thyroid Disease ◽

Autoimmune Thyroid Disease ◽

Good Reason ◽

The Body ◽

Autoimmune Thyroid Diseases ◽

Autoimmune Thyroid ◽

Organ Specific

Introduction, Autoimmune diseases are chronic conditions initiated by the loss of immunological tolerance to self-antigens. They constitute heterogeneous group of disorders, in which multiple alterations in the immune system result in a spectrum of syndromes that either target specific organs or affect the body systematically. Recent epidemiological studies have shown a possible shift of one autoimmune disease to another or the fact that more than one autoimmune disease may coexist in a single patient or in the same family. Numerous autoimmune diseases have been shown to coexist frequently with thyroid autoimmune diseases. Autoimmune thyroid disease and other organ specific non-endocrine autoimmune diseases. This part of the study reviews the prevalence of autoimmune thyroid disease coexisting with: pernicious anaemia, vitiligo, celiac disease, autoimmune liver disease, miastenia gravis, alopecia areata and sclerosis multiplex, and several recommendations for screening have been given. Autoimmune thyroid disease and other organ non-specific non-endocrine autoimmune diseases. Special attention is given to the correlation between autoimmune thyroid disease and rheumatoid arthritis, systemic lupus erythematosus, syndrome Sj?gren, systemic sclerosis and mixed connective tissue disease. Conclusions. Screening for autoimmune thyroid diseases should be recommended in everyday clinical practice, in patients with primary organ-specific or organ non-specific autoimmune disease. Other?wise, in patients with primary thyroid autoimmune disease, there is no good reason of seeking for all other autoimmune diseases, although these patients have a greater risk of developing other autoimmune disease. Economic aspects of medicine require further analyzing of these data, from cost/benefit point of view to justified either mandatory screening or medical practitioner judgment.

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Predictive Metagenomic Analysis of Autoimmune Disease Identifies Robust Autoimmunity and Disease Specific Microbial Signatures

10.1101/779967 ◽

2019 ◽

Author(s):

Angelina Volkova ◽

Kelly V. Ruggles

Keyword(s):

Random Forest ◽

Autoimmune Disease ◽

Autoimmune Diseases ◽

Gut Microbiome ◽

Multidimensional Data ◽

Support Vector ◽

Control Analysis ◽

Extreme Gradient Boosting ◽

Random Forest Tree ◽

Disease Specific

ABSTRACTWithin the last decade, numerous studies have demonstrated changes in the gut microbiome associated with specific autoimmune diseases. Due to differences in study design, data quality control, analysis and statistical methods, many results of these studies are inconsistent and incomparable. To better understand the relationship between the intestinal microbiome and autoimmunity, we have completed a comprehensive re-analysis of 42 studies focusing on the gut microbiome in twelve autoimmune diseases to identify a microbial signature predictive of multiple sclerosis (MS), inflammatory bowel disease (IBD), rheumatoid arthritis (RA) and general autoimmune disease using both 16S rRNA sequencing data and shotgun metagenomics data. To do this, we used four machine learning algorithms, random forest, eXtreme Gradient Boosting (XGBoost), ridge regression and support vector machine with radial kernel and recursive feature elimination to rank disease predictive taxa comparing disease vs. healthy participants and pairwise comparisons of each disease. Comparing the performance of these models, we found XGBoost and random forest, tree-based methods capable of handling sparse multidimensional data, to consistently produce the best results. Through this modeling, we identified a number of taxa consistently identified as dysregulated in a general autoimmune disease model including Odoribacter, Lachnospiraceae Clostridium and Mogibacteriaceae implicating all as potential factors connecting the gut microbiome and to autoimmune response. Further, we computed pairwise comparison models to identify disease specific taxa signatures highlighting a role for Peptostreptococcaceae and Ruminococcaceae Gemmiger in IBD and Akkermansia, Butyricicoccus and Mogibacteriaceae in MS. We then connected a subset of these taxa with potential metabolic alterations based on metagenomic/metabolomic correlation analysis, identifying 250 metabolites associated with autoimmunity-predictive taxa.

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Early recurrence or persistence of autoimmune diseases after unmanipulated autologous stem cell transplantation

Blood ◽

10.1182/blood.v88.9.3621.bloodjournal8893621 ◽

1996 ◽

Vol 88 (9) ◽

pp. 3621-3625 ◽

Cited By ~ 143

Author(s):

HH Euler ◽

AM Marmont ◽

A Bacigalupo ◽

S Fastenrath ◽

P Dreger ◽

...

Keyword(s):

Stem Cell ◽

Autoimmune Disease ◽

Stem Cell Transplantation ◽

Autoimmune Diseases ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Lupus Erythematosus ◽

Clinical Signs ◽

High Dose

Autologous stem cell transplantation with or without in vitro lymphocyte depletion has been suggested as a new treatment option for severe autoimmune diseases. We describe five patients with autoimmune diseases (CREST syndrome, myasthenia gravis and Hashimoto's thyroiditis, systemic lupus erythematosus, atopic dermatitis, and rheumatoid arthritis) who underwent autologous bone marrow (n = 1) or peripheral blood progenitor cell (n = 4) transplantation with unmanipulated grafts as treatment for the autoimmune disease in one case or as treatment for a malignant disorder with a concomitant autoimmune disorder in four cases. In all patients serological and clinical signs of the autoimmune disease recurred early or persisted. These observations should be regarded as a cautionary note concerning the efficacy of high-dose therapy followed by transplantation of unmanipulated autologous stem cells for treatment of severe autoimmune diseases.

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Treatment of Severe Autoimmune Diseases with Autologous Hematopoietic Stem Cell Transplantation

Macedonian Medical Review ◽

10.1515/mmr-2017-0003 ◽

2017 ◽

Vol 71 (1) ◽

pp. 10-14

Author(s):

Zlate Stojanoski ◽

Anzelika Karadzova-Stojanoska ◽

Aleksandra Pivkova-Veljanovska ◽

Sonja Genadieva-Stavrik ◽

Lazar Cadievski ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Multiple Myeloma ◽

Stem Cell ◽

Autoimmune Disease ◽

Stem Cell Transplantation ◽

Autoimmune Diseases ◽

Cell Transplantation ◽

Lupus Erythematosus ◽

Systemic Lupus

Abstract Introduction. Autoimmune diseases are a family of more than 100 heterogeneous conditions that affect 5 to 8% of the world’s population. The etiology is still un-known but the disregulation of the regulatory T-lymphocytes play a central role inthe autoimmunity and the success of the long-term remission. Although conventional immunosuppression and new biological agents can provide disease control in severely affected patients, such treatments are rarely curative and alternative strategies are needed. Indeed, severe forms of systemic autoimmune diseases, such as multiple sclerosis (MS), systemic sclerosis (SSc), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), juvenile idiopathic arthritis (JIA), hematologic immune cytopenia (HIC) and Crohn’s disease are difficult to be treated. High-dose immunosuppressive therapy followed by autologous stem cells transplantation is reliable option for a successive treatment of this group of patients. Aim. To determine the safety of the procedure of autologous stem cell transplantation in patients with autoimmune diseases and concomitant malignant hematological disorders. Methods. During a period of 15 years (from September 2000 to September 2015) at the University Clinic of Hematology in Skopje we have treated 6 patients with autoimmune disease and concomitant hematological neoplasm. None of the patients was treated for primary autoimmune diseases. Two men and 4 women, with median age of 47 years were treated. Sjogren syndrome and multiple myeloma were found in 2 patients, polyartheritis nodosa and multiple myeloma in 1 patient, rheumatoid arthritis and acute myeloblastic leukemia in 1, systemic lupus erythematosus and non-Hodgkin lymphoma in 1; severe psoriasis and acute myeloblastic leukemia in 1 patient. Results. All treated patients are alive after trans-planted procedure, with transplant related mortality day +100: 0. Conclusion. Autologous stem cell transplantation is safe and recommended option for treatment ofpatients with autoimmune disease and hematologic neoplasm.

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Immunotherapy to treat malignancy in patients with pre-existing autoimmunity

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2019-000356 ◽

2020 ◽

Vol 8 (1) ◽

pp. e000356 ◽

Cited By ~ 3

Author(s):

Patrick Boland ◽

Anna C Pavlick ◽

Jeffrey Weber ◽

Sabina Sandigursky

Keyword(s):

Autoimmune Disease ◽

Autoimmune Diseases ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Retrospective Data ◽

Prospective Data ◽

The Past ◽

Increased Risk ◽

Autoimmune Conditions ◽

The Relationship

In the past 10 years, immune checkpoint inhibitors (ICIs) have become an additional pillar of cancer therapy by activating the immune system to treat a number of different malignancies. Many patients receiving ICIs develop immune-related adverse events (irAEs) that mimic some features of classical autoimmune diseases. Unfortunately, patients with underlying autoimmune conditions, many of whom have an increased risk for malignancy, have been excluded from clinical trials of ICIs due to a concern that they will have an increased risk of irAEs. Retrospective data from patients with autoimmune diseases and concomitant malignancy treated with ICIs are encouraging and suggest that ICIs may be tolerated safely in patients with specific autoimmune diseases, but there are no prospective data to guide management. In this manuscript, we review the relationship between pre-existing autoimmune disease and irAEs from checkpoint inhibitors. In addition, we assess the likelihood of autoimmune disease exacerbations in patients with pre-existing autoimmunity receiving ICI.

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Autoantibodies persist in relatives to systemic lupus erythematosus patients during 12 years follow-up

Lupus ◽

10.1177/0961203316676378 ◽

2016 ◽

Vol 26 (7) ◽

pp. 723-728 ◽

Cited By ~ 1

Author(s):

H Langkilde ◽

A Voss ◽

N Heegaard ◽

H Laustrup

Keyword(s):

Systemic Lupus Erythematosus ◽

Autoimmune Disease ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Population Based ◽

Systemic Lupus ◽

Autoantibody Production ◽

Increased Risk ◽

Reported Health

Background Systemic lupus erythematosus (SLE) is an autoimmune disease with presence of autoantibodies and characteristic multi-organ involvement. Relatives of SLE patients have an increased risk of autoantibody production and autoimmune diseases. Methods In 2001, 226 first degree relatives (FDRs) of a population-based cohort of SLE patients were examined for the prevalence of autoantibodies and self-reported health complaints. In 2013, 143 FDRs were re-investigated and deceased’s medical records were examined. Results Participants and non-participants were comparable regarding baseline characteristics, while deceased FDRs were older than participants, but with comparable ANA status. ANA status at baseline correlated to ANA status at follow-up. At follow-up, two FDRs reported SLE and 15 FDRs other autoimmune diseases. No observation at baseline alone could predict self-reported health. During follow-up 33 died at median age 76 years. Three deceased FDRs were diagnosed with an autoimmune disease. Conclusion The study showed that FDRs of SLE patients have an increased prevalence of ANA compared to healthy controls. The prevalence increased during follow-up, and ANA positive FDRs at baseline were prone to be ANA positive at follow-up. ANA positive FDRs had more self-reported autoimmune diseases, including SLE and rheumatoid arthritis, than reported from other population-based investigations.

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AB1051 KIKUCHI FUJIMOTO DISEASE, IS IT SLE?

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.5460 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1815.3-1816

Author(s):

J. Camins-Fàbregas ◽

V. Ortiz-Santamaria ◽

N. Busquets-Pérez ◽

A. Cuervo ◽

I. Cañas Alcántara ◽

...

Keyword(s):

Autoimmune Disease ◽

Autoimmune Diseases ◽

Lupus Erythematosus ◽

Clinical Manifestations ◽

Response To Treatment ◽

Systemic Autoimmune Disease ◽

Histiocytic Necrotizing Lymphadenitis ◽

Systemic Autoimmune Diseases ◽

Necrotizing Lymphadenitis

Background:Kikuchi-Fujimoto disease (KFD) is a rare entity characterized by adenopathies and fever. It raises a broad differential diagnosis that includes lymphoproliferative disorders, infections and systemic autoimmune diseases, and diagnostic confirmation is always by histology, which shows histiocytic necrotizing lymphadenitis. Although its course is generally benign and self-limited, it can be associated both at the time of diagnosis and during follow-up with systemic autoimmune diseases, the most frequent of which is systemic lupus erythematosus (SLE).Objectives:To describre the clinical and analytical characteristics of patients diagnosed with KFD and the development of systemic autoimmune disease.Methods:Patients diagnosed with KFD during the 1990s and 2020s are collected in a regional hospital (Granollers General Hospital). The clinic is documented at the diagnosis of EKF, the appearance of systemic autoimmune disease during follow-up and its clinical and analytical characteristics.Results:A total of 7 patients with EKF were diagnosed. All of them women with a mean age at diagnosis of 30 years. Diagnosis was made in all cases with compatible clinical symptoms, fever and lymphadenopathy, and lymph node biopsy confirming histiocytic necrotizing lymphadenitis. At the time of diagnosis, a patient was also diagnosed with SLE. During the follow-up, 4 of the 6 remaining patients developed clinical manifestations compatible with SLE (3 of them with systemic manifestations and a case of subacute cutaneous lupus. The mean time of onset of SLE was 34 months (between 6 months and 5 years). All of them received treatment with hydroxychloroquine, with good response to treatment.The clinical and analytical characteristics are presented in Table 1 below.Conclusion:In our center, 5 of the 7 patients (71%) diagnosed with EKF developed manifestations compatible with SLE. The importance of the diagnosis of EKF lies precisely in the possible association with systemic autoimmune disease, the most common being SLE, so it is recommended that patients be monitored to identify those who develop associated autoimmune disease.Disclosure of Interests:None declared

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