Induction of De Novo Autoimmune Disease in Normal Mice upon Repeated Immunization with Antigen

2014 ◽  
pp. 85-90 ◽  
Author(s):  
Ken Tsumiyama ◽  
Shunichi Shiozawa
Keyword(s):  
Autoimmune Disease ◽  
De Novo

scholarly journals Transforming Growth Factor β and CD25 Are Important for Controlling Systemic Dissemination following Yersiniaenterocolitica Infection of the Gut

2010 ◽  
Vol 78 (9) ◽  
pp. 3716-3725 ◽  
Author(s):  
Youmin Zhong ◽  
Angelene Cantwell ◽  
Peter H. Dube
Keyword(s):  
Growth Factor ◽  
Autoimmune Disease ◽  
Bacterial Infection ◽  
Yersinia Enterocolitica ◽  
Transforming Growth Factor ◽  
De Novo ◽  
Inflammatory Responses ◽  
Acute Infection ◽  
Transforming Growth Factor Β ◽  
Mesenteric Lymph Nodes

ABSTRACT Infection of the gut by invasive bacterial pathogens leads to robust inflammatory responses that if left unchecked can lead to autoimmune disease and other sequelae. How the immune system controls inflammation and limits collateral damage to the host during acute bacterial infection is poorly understood. Here, we report that antibody-mediated neutralization of transforming growth factor β (TGF-β) prior to infection with the model enteric pathogen Yersinia enterocolitica reduces the mean time to death by 1 day (P = 0.001), leads to rapid colonization of the liver and lung, and is associated with exacerbation of inflammatory histopathology. During Yersinia enterocolitica infection CD4+ cells are the source of de novo TGF-β transcription in the Peyer's patches, mesenteric lymph nodes, and spleen. Correspondingly there is both antigen-specific and -independent expansion of CD4+ CD25+ Foxp3+ and TGF-β+ T-regulatory cells (T-regs) after Yersinia infection that is reduced in ovalbumin T-cell receptor-restricted OT-II mice. Functional inactivation of CD25 by anti-CD25 treatment results in more rapid death, dissemination of the bacteria to the liver and lungs, and exacerbated inflammatory histopathology, similar to what is seen during TGF-β neutralization. Altogether, these data suggest that TGF-β produced by T-regs is important in restricting bacteria during the acute phase of invasive bacterial infection of the gut. These data expand the roles of T-regs to include tempering inflammation during acute infection in addition to the well-established roles of T-regs in chronic infection, control of immune homeostasis, and autoimmune disease.

Prospective Multicenter Study for Patients with Therapy - Related Acute Myeloid Leukemia (AML) Using Intensive Induction and Postremission Therapy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2001-2001
Author(s):  
Bernhard Josef Wormann ◽  
Claudia Schoch ◽  
Albrecht Reichle ◽  
Peter Staib ◽  
Wolf-Dieter Ludwig ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
Survival Rate ◽  
Autoimmune Disease ◽  
Median Survival ◽  
Myeloid Leukemia ◽  
De Novo ◽  
Postremission Therapy ◽  
De Novo Aml ◽  
Acute Myeloid

Abstract Therapy - related acute myeloid leukemia (t-AML) is one of the most severe long - term complications of successful cancer treatment using chemo- and/or radiotherapy. Its frequency is increasing, also in patients with autoimmune disease after cytostatic therapy. Cytogenetic and molecular biological analysis have identified several subgroups, however large prospective trials on optimal treatment are lacking. In 1999 the German AMLCG started a prospective multicenter randomized trial including patients with t-AML. Patients received induction treatment, randomized to either TAD (standard dose thioguanine, araC, daunorubicin) followed by HAM (HAM, high-dose araC 1 or 3 g/m2x6/mitoxantrone 10mg/m2x3), or to induction by two courses of HAM. Above the age of 60 years, the second induction course was given only to patients with 5 % or more residual bone marrow blasts. Postremission therapy was randomized to either TAD followed by three year maintenance, or to autologous stem cell transplantation. Patients under the age of 60 years with a suitable donor received an allogeneic stem cell transplantation. 137 patients were included. The most frequent primary diagnoses were breast cancer (n = 43), Non Hodgkin’s lymphoma (n = 18), Hodgkin’s lymphoma (n = 9), autoimmune disease (n = 9), multiple myeloma (n = 5), germ cell tumor (n = 5) and ovarian cancer (n = 5). The median age was 57 years (23 – 77). 64 of 119 currently evaluable patients achieved CR (53,8 %), 34 (29 %) had persistent leukaemia, 20 (17,1 %) were classified as early death without evidence of disease. The CR rate was significantly lower than in 1532 patients with de novo AML (65,6 %), but higher than in patients with AML after MDS (46,8 %). Cytogenetic analysis was routinely performed in all patients with t-AML. 21 (17,7 %) had a favourable karyotype, 47 (39,5 %) an unfavourable karyotype, 51 (42,9 %) were classified as intermediate. Patients with favourable karyotype had a median survival of 25 months and an estimated survival rate at 5 yrs of 47,4 %. Median survival was 3 months for patients with unfavourable karyotype with an estimated survival rate of 12,5 %, while the intermediate group had a median survival of 19 months and an estimated survival rate of 24,2 %. This is one of the largest prospective studies on the therapy of patients with t-AML. The CR rate of all patients was inferior to patients with de novo AML. However, this difference was mainly due to the high number of patients with unfavourable karyotype. Within cytogenetically defined subgroups, the prognosis of t-AML patients does not differ significantly from patients with de novo AML.

scholarly journals Case Report: Infantile Ischemic Stroke and Antiphospholipid Antibodies, Description of Four Cases

2020 ◽  
Vol 8 ◽  
Author(s):  
Teresa Giani ◽  
Angela Mauro ◽  
Giovanna Ferrara ◽  
Rolando Cimaz
Keyword(s):  
Ischemic Stroke ◽  
Case Report ◽  
Autoimmune Disease ◽  
Antiphospholipid Syndrome ◽  
Antiphospholipid Antibodies ◽  
De Novo ◽  
Rare Condition ◽  
Gray Zone ◽  
Transplacental Passage ◽  
Perinatal Stroke

Antiphospholipid syndrome (APS) is a rare condition in childhood, but even more in the neonatal age. Most neonatal cases are considered a passively acquired autoimmune disease, due to a transplacental passage of maternal antiphospholipid antibodies (aPL) from mothers with primary or secondary APS or, more often, from asymptomatic aPL carriers. Exceedingly unusual is the neonatal de novo production of aPL. We present four infants with presumed perinatal stroke in presence of increased and persistent aPL levels, even after 6 months of life, opening the window on a gray zone related to the origin of these antibodies (maternal or neonatal) and on their role in the pathogenesis of stroke.

scholarly journals Maternal Autoantibody Triggers De Novo T Cell-Mediated Neonatal Autoimmune Disease

2003 ◽  
Vol 170 (9) ◽  
pp. 4656-4664 ◽  
Author(s):  
Yulius Y. Setiady ◽  
Eileen T. Samy ◽  
Kenneth S. K. Tung
Keyword(s):  
T Cell ◽  
Autoimmune Disease ◽  
De Novo

Prenatal Autoimmune Disease, Multisystem, Infantile Onset-like Phenotype and Proximal Renal Tubular Dysplasia Associated With STAT3 Mutation

2019 ◽  
Vol 23 (4) ◽  
pp. 306-311
Author(s):  
Jefferson Terry ◽  
Sylvie Langlois ◽  
Rosemarie Rupps ◽  
Harinder Gill
Keyword(s):  
Autoimmune Disease ◽  
De Novo ◽  
Autoimmune Disorder ◽  
Stat3 Mutation ◽  
Renal Tubular ◽  
The Impact ◽  
Transcription 3 ◽  
Stat3 Mutations ◽  
Immunological Abnormalities ◽  
Autoimmune Phenomena

Activating heterozygous germline mutations in the signal transducer and activator of transcription 3 ( STAT3) gene are associated with the rare autoimmune disorder autoimmune disease, multisystem, infantile onset (ADMIO). The phenotype of ADMIO is typified by hypogammaglobulinemia and onset of autoimmune phenomena during early childhood that include diabetes and autoimmune enteritis. This case report describes in utero onset of precocious lymphocyte maturation, autoimmune enteropathy-like inflammation, and proximal renal tubular dysplasia associated with a novel de novo heterozygous STAT3 mutation. The findings expand the phenotype associated with activating STAT3 mutations and suggest that the impact of the immunological abnormalities associated with ADMIO can begin prior to birth.

scholarly journals Systemic Lupus Erythematosus and Virus C Infection - Diagnosis, Evolution and Treatment Particularities

2020 ◽  
Vol 17 (5) ◽  
pp. 15-33
Author(s):  
Delia-Georgiana Tudorovici Rotariu ◽  
Mircea Penescu
Keyword(s):  
Autoimmune Disease ◽  
Lupus Erythematosus ◽  
De Novo ◽  
Treatment Options ◽  
Immunosuppressive Drug ◽  
Lower Survival Rate ◽  
Increased Risk ◽  
Virus C ◽  
Stage Renal Disease ◽  
Direct Acting

Abstract Lupus erythematosus (SLE) is an autoimmune disease with a broad spectrum of clinical and immunologic manifestations. Hepatitis C virus (HCV) has been postulated as a potential etiologic or triggering agent among other viruses and it appears to be associated with the presence of autoimmune disorders, even mimicking SLE clinically and serologically. Data on the association between HCV infection and SLE are scarce, but an interaction between these two conditions seems possible. As for treatment options, it is well known that the classic antiviral therapy with interferon may aggravate preexisting autoimmunity, unmask previously silent autoimmune processes, or even cause the emergence of de novo autoimmune disease, including SLE. Interferon-free treatment seems to be more efficacious, safer and more tolerable. However, it is important that clinicians be aware that DAAs (direct acting antivirals) can also trigger lupus-like immune complex-mediated glomerulonephritis. There is scant data on the use of immunosuppressive drug therapy in HCV patients. It seems that enhanced HCV replication due to immunosuppression does not lead to clinically significant sequelae and growing evidence has been reported that supports its efficacy and safety. Patients with SLE and virus C infection are a special category, a fact that the clinician needs to take in consideration in order to a better approach, all the more as these patients are at increased risk for developing end-stage renal disease and have a lower survival rate than general population.

scholarly journals Rigorous estimation of post-translational proteasomal splicing in the immunopeptidome

2021 ◽  
Author(s):  
Kamil J Cygan ◽  
Ehdieh Khaledian ◽  
Lili Blumenberg ◽  
Robert R Salzler ◽  
Darshit Shah ◽  
...  
Keyword(s):  
Immune Response ◽  
Autoimmune Disease ◽  
De Novo ◽  
Critical Role ◽  
Unknown Origin ◽  
Peptide Sequencing ◽  
De Novo Peptide Sequencing ◽  
De Novo Peptide

Recently, de novo peptide sequencing has made it possible to gain new insights into the human immunopeptidome without relying on peptide databases, while identifying peptides of unknown origin. Many recent studies have attributed post-translational proteasomal splicing as the origin of those peptides. Here, we describe a peptide source assignment workflow to rigorously assign the source of de novo sequenced peptides and find that the estimated extent of post-translational splicing in the immunopeptidome is much lower than previously reported. Our approach demonstrates that many peptides that were thought to be post-translationally spliced are likely linear peptides, and many peptides that were thought to be trans-spliced could be cis-spliced. We believe our approach furthers the understanding of post-translationally spliced peptides and thus improves the characterization of immunopeptidome which plays a critical role in the immune response to antigens in cancer, autoimmune disease, and infections.

scholarly journals OP0126 IS IMMUNE CHECKPOINT INHIBITORS THERAPIES SAFE AND EFFECTIVE FOR PATIENTS WITH CANCER AND PREEXISTING AUTOIMMUNE DISEASE?

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 83.2-83
Author(s):  
W. Xie ◽  
H. Huang ◽  
Z. Zhang
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Disease ◽  
Random Effects ◽  
Observational Studies ◽  
Immune Checkpoint Inhibitors ◽  
De Novo ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Patients With Cancer

Background:Immune checkpoints inhibitors (ICIs) are associated with frequent immune-related adverse events (irAEs). Most patients with preexisting autoimmune disease (PAD) have been universally excluded from clinical trials and ICIs are not recommended for patients with cancer and PAD due to the unknown safety. In this study, we aim to evaluate the safety and efficacy of ICIs in patients with PAD and cancer.Objectives:Systematic searches were performed of PubMed, EMBASE, and the Cochrane library from inception through September 2019 for observational studies reporting safety and efficacy data among ICIs-treated patients with cancer and PAD. A random effects meta-analysis was performed to calculate pooled incidence rates of PAD flare, irAEs and response.Methods:Systematical search of PubMed, EMBASE and Cochrane Library plus a hand search of conference proceedings were performed for observational studies that reported cancer incidence in patients with RA treated with biologics or tofacitinib with active comparator of conventional DMARDs (csDMARDs) or TNFi. The pooled relative risk (RR) and 95% confidence interval (CI) were calculated with fix-effects or random-effects model.Results:A total of 619 ICI-treated patients with PAD in 14 publications were finally identified. In the random effects meta-analysis, pooled incidence of PAD flares,de novoirAEs or both of any grade was 60% (95% CI 52%-68%). Viewed separately, there were 219 and 206 patients experiencing PAD exacerbation andde novoirAEs of any grade, yielding a pooled incidence of 35% (95% CI 29%-41%) and 33% (95% CI 24%-42%) respectively. Of these, most of flare andde novoirAEs were graded as mild (grade 1-2) (pooled proportion: 82%, 95%CI 72%-91%; 65%, 95%CI 54%-76%, respectively). Rheumatoid arthritis was associated with a trend toward higher flare occurrence compared with another individual PADs (RR=1.25-1.88). With respect to efficacy, 136 patients showed complete or partial response, corresponding to a pooled response rates of 30% (95% CI 22%-39%). There were no statistical differences between patients with and without immunosuppressive therapy at ICI start regarding flare (RR: 1.08, 95% CI 0.72-1.62), but a trend towards lower response rates was observed in patients with baseline immunosuppressants (RR: 0.58, 95% CI 0.26-1.33).Conclusion:Immune toxicities are frequent in ICI-treated patients with PAD but often mild and manageable without discontinuing therapy. Rheumatoid arthritis is associated with a trend toward more flares. ICI treatment are effective and not absolute contraindication in PAD patients, but close monitoring and multidisciplinary collaboration should be contemplated, especially for those concomitantly receiving immunosuppressant or having rheumatoid arthritis.References:[1]Khan SA, Pruitt SL, Xuan L et al. Prevalence of autoimmune disease among patients with lung cancer: Implications for immunotherapy treatment options. JAMA Oncol 2016;2:1507-1508.Figure 1.Pooled effect estimates in ICI-treated patient with PAD (A) PAD flare,de novoirAEs or both; (B) PAD flare; (C)de novoirAEs. ICI: Immune checkpoint inhibitors; PAD: Preexisting autoimmune disease; irAEs: Immune-related adverse events.Disclosure of Interests:None declared

The Morphology of the Rat Kidney Following Folic Acid Administration

1970 ◽  
Vol 28 ◽  
pp. 200-201
Author(s):  
Aline Byrnes ◽  
Elsa E. Ramos ◽  
Minoru Suzuki ◽  
E.D. Mayfield
Keyword(s):  
Folic Acid ◽  
De Novo ◽  
Specific Activity ◽  
Rat Kidney ◽  
Present Report ◽  
Intracellular Localization ◽  
Male Rats ◽  
Renal Hypertrophy ◽  
Electron Microscopic ◽  
Biochemical Alterations

Renal hypertrophy was induced in 100 g male rats by the injection of 250 mg folic acid (FA) dissolved in 0.3 M NaHCO3/kg body weight (i.v.). Preliminary studies of the biochemical alterations in ribonucleic acid (RNA) metabolism of the renal tissue have been reported recently (1). They are: RNA content and concentration, orotic acid-c14 incorporation into RNA and acid soluble nucleotide pool, intracellular localization of the newly synthesized RNA, and the specific activity of enzymes of the de novo pyrimidine biosynthesis pathway. The present report describes the light and electron microscopic observations in these animals. For light microscopy, kidney slices were fixed in formalin, embedded, sectioned, and stained with H & E and PAS.

Early ossicle growth in the regenerating disc of a brittle star

1994 ◽  
Vol 52 ◽  
pp. 364-365
Author(s):  
M. Shlepr ◽  
R. L. Turner
Keyword(s):  
Cell Membrane ◽  
Light Microscopy ◽  
De Novo ◽  
Current Model ◽  
Syncytium Formation ◽  
Brittle Star ◽  
Intracellular Location ◽  
Limited Volume ◽  
Tissue Calcification

Calcification in the echinoderms occurs within a limited-volume cavity enclosed by cytoplasmic extensions of the mineral depositing cells, the sclerocytes. The current model of this process maintains that the sheath formed from these cytoplasmic extensions is syncytial. Prior studies indicate that syncytium formation might be dependent on sclerocyte density and not required for calcification. This model further envisions that ossicles formed de novo nucleate and grow intracellularly until the ossicle effectively outgrows the vacuole. Continued ossicle growth occurs within the sheath but external to the cell membrane. The initial intracellular location has been confirmed only for elements of the echinoid tooth.The regenerating aboral disc integument of ophiophragmus filograneus was used to test the current echinoderm calcification model. This tissue is free of calcite fragments, thus avoiding questions of cellular engulfment, and ossicles are formed de novo. The tissue calcification pattern was followed by light microscopy in both living and fixed preparations.

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