Manish Butte

The potential role of tRNAs and small RNAs derived from tRNAs in the occurrence and development of systemic lupus erythematosus.

May 20, 2020 By Manish Butte

The potential role of tRNAs and small RNAs derived from tRNAs in the occurrence and development of systemic lupus erythematosus.

Biochem Biophys Res Commun. 2020 May 15;:

Authors: Xu H, Chen W, Zheng F, Tang D, Dai W, Huang S, Zhang C, Zeng J, Wang G, Dai Y

Abstract
BACKGROUND: Emerging evidence has shown the involvement of dysregulated transfer RNAs (tRNAs) and small RNAs derived from transfer RNAs (tsRNAs) in the pathophysiology of human diseases. The role of tRNAs and tsRNAs in systemic lupus erythematosus (SLE) remains unclear. Therefore, this study aims to investigate the possible regulatory roles of tRNAs and tsRNAs in the pathological mechanism of SLE.
METHODS: Total RNA was extracted from peripheral blood mononuclear cells (PBMCs) of 20 SLE patients and 20 normal controls (NCs) to obtain tRNAs and tsRNAs, followed by tRNA and tsRNA expression profiling by the NextSeq system. Target genes were predicted by informatics analysis. Subsequently, to explore the function of messenger RNA (mRNA) in these target genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed using the Cytoscape plug-in BinGo, the DAVID database, and Cytoscape software.
RESULTS: A total of 101 tRNAs and 355 tsRNAs were found to be differentially expressed in SLE patients versus NCs by RNA microarray. GO analysis revealed that the altered target genes of the selected tRNAs and tsRNAs were most enriched similarly in immune response and the immune system process. Moreover, KEGG pathway analysis demonstrated that altered target genes of tRNAs were most enriched in systemic lupus erythematosus, while the altered target genes of tsRNAs were most enriched in the T cell receptor signalling pathway, Th1 and Th2 cell differentiation and primary immunodeficiency. These pathways may be related to the initiation of SLE.
CONCLUSION: Our results provide a novel perspective for studying the tRNA-related and tsRNA-related pathogenesis of SLE.

PMID: 32423797 [PubMed – as supplied by publisher]

From Dysgammaglobulinemia to Autosomal-Dominant Activation-Induced Cytidine Deaminase Deficiency: Unraveling an Inherited Immunodeficiency after 50 Years.

May 20, 2020 By Manish Butte

From Dysgammaglobulinemia to Autosomal-Dominant Activation-Induced Cytidine Deaminase Deficiency: Unraveling an Inherited Immunodeficiency after 50 Years.

J Pediatr. 2020 May 15;:

Authors: Fadlallah J, Chentout L, Boisson B, Pouliet A, Masson C, Morin F, Durandy A, Casanova JL, Oksenhendler E, Kracker S

Abstract
The genetic investigation of a family presenting with a dominant form of hyper IgM syndrome published in 1963 and 1975 revealed a R190X nonsense mutation in activation-induced cytidine deaminase. This report illustrates the progress made over 6 decades in the characterization of primary immunodeficiencies, from immunochemistry to whole-exome sequencing.

PMID: 32423680 [PubMed – as supplied by publisher]

Retropharyngeal internal carotid artery: a review of three cases.

May 20, 2020 By Manish Butte

Retropharyngeal internal carotid artery: a review of three cases.

Oral Maxillofac Surg. 2020 Jun;24(2):255-261

Authors: Garrido MB, Jagtap R, Hansen M

Abstract
INTRODUCTION: The internal carotid artery (ICA) can take multiple pathways as it extends from the carotid bifurcation to the skull base. An aberration of its normal pathway may place the ICA in a retropharyngeal position in close proximity to the posterior pharyngeal wall. Radiographic classification is based on its proximity to the pharynx and/or pathway. We present a series of three cases of retropharyngeal ICAs, our goal is to report and classify these variations.
CASE PRESENTATION: CASE 1: Retropharyngeal right ICA. Minimum distance to the pharyngeal wall was ~ 4.9 mm (high risk of vascular injury) with a tortuous pathway. CASE 2: Bilateral retropharyngeal ICA. ICAs were in contact with the posterior pharyngeal wall (very high risk of vascular injury). The left has a kinking pathway, the right tortuous. CASE 3: Bilateral retropharyngeal ICA. Minimum distances of the right and left ICAs to the posterior pharyngeal wall were ~ 3.5 mm and ~ 3.3 mm, respectively (high risk of vascular injury). The right has a kinking pathway, the left tortuous.
DISCUSSION: Closeness of the vessel to the retropharyngeal wall increases the risk of surgical and non-surgical complications. Noteworthy is that the position of the artery is not constant and can change in position over periods of time.
CONCLUSION: Knowledge of the anatomy and variations of the ICA is important for oral and maxillofacial radiologists and surgeons to enable clinicians to take necessary precautions to decrease complications if performing any procedure in the region.

PMID: 32314074 [PubMed – indexed for MEDLINE]

Combined immunodeficiency in a patient with c-Rel deficiency.

May 20, 2020 By Manish Butte

Combined immunodeficiency in a patient with c-Rel deficiency.

J Allergy Clin Immunol. 2019 08;144(2):606-608.e4

Authors: Beaussant-Cohen S, Jaber F, Massaad MJ, Weeks S, Jones J, Alosaimi MF, Wallace J, Al-Herz W, Geha RS, Chou J

PMID: 31103457 [PubMed – indexed for MEDLINE]

Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies.

May 20, 2020 By Manish Butte

Double-blind, placebo-controlled, randomized trial on low-dose azithromycin prophylaxis in patients with primary antibody deficiencies.

J Allergy Clin Immunol. 2019 08;144(2):584-593.e7

Authors: Milito C, Pulvirenti F, Cinetto F, Lougaris V, Soresina A, Pecoraro A, Vultaggio A, Carrabba M, Lassandro G, Plebani A, Spadaro G, Matucci A, Fabio G, Dellepiane RM, Martire B, Agostini C, Abeni D, Tabolli S, Quinti I

Abstract
BACKGROUND: Lacking protective antibodies, patients with primary antibody deficiencies (PADs) experience frequent respiratory tract infections, leading to chronic pulmonary damage. Macrolide prophylaxis has proved effective in patients with chronic respiratory diseases.
OBJECTIVE: We aimed to test the efficacy and safety of orally administered low-dose azithromycin prophylaxis in patients with PADs.
METHODS: We designed a 3-year, double-blind, placebo-controlled, randomized clinical trial to test whether oral azithromycin (250 mg administered once daily 3 times a week for 2 years) would reduce respiratory exacerbations in patients with PADs and chronic infection-related pulmonary diseases. The primary end point was the number of annual respiratory exacerbations. Secondary end points included time to first exacerbation, additional antibiotic courses, number of hospitalizations, and safety.
RESULTS: Eighty-nine patients received azithromycin (n = 44) or placebo (n = 45). The number of exacerbations was 3.6 (95% CI, 2.5-4.7) per patient-year in the azithromycin arm and 5.2 (95% CI, 4.1-6.4) per patient-year in the placebo arm (P = .02). In the azithromycin group the hazard risk for having an acute exacerbation was 0.5 (95% CI, 0.3-0.9; P = .03), and the hazard risk for hospitalization was 0.5 (95% CI, 0.2-1.1; P = .04). The rate of additional antibiotic treatment per patient-year was 2.3 (95% CI, 2.1-3.4) in the intervention group and 3.6 (95% CI, 2.9-4.3) in the placebo group (P = .004). Haemophilus influenzae and Streptococcus pneumoniae were the prevalent isolates, and they were not susceptible to macrolides in 25% of patients of both arms. Azithromycin’s safety profile was comparable with that of placebo.
CONCLUSION: The study reached the main outcome centered on the reduction of exacerbation episodes per patient-year, with a consequent reduction in additional courses of antibiotics and risk of hospitalization.

PMID: 30910492 [PubMed – indexed for MEDLINE]

A Multicenter Prospective Survey on Early-Onset Inflammatory Bowel Disease in Japan.

May 19, 2020 By Manish Butte

A Multicenter Prospective Survey on Early-Onset Inflammatory Bowel Disease in Japan.

Digestion. 2020 May 18;:1-9

Authors: Kudo T, Fujii T, Maisawa SI, Sasaki M, Uchida K, Ida S, Kagimoto S, Yoden A, Shimizu T

Abstract
INTRODUCTION: The incidence of early-onset inflammatory bowel disease is increasing in Japan.
OBJECTIVE: This study aimed to analyze the treatment and progress of early-onset inflammatory bowel disease.
METHODS: This prospective survey evaluated the data of 43 patients aged <8 years who were diagnosed with inflammatory bowel disease (IBD) from the time of diagnosis to 36 months after registration.
RESULTS: A total of 12 patients with Crohn’s disease (CD), 21 with ulcerative colitis (UC), and 3 with unclassified IBD were enrolled. The mean disease onset age was 3 years and 7 months. Colon and anal lesions were present in 100 and 50% of patients with CD, respectively. Granulomas were detected in 5 patients (41.7%). Dietary elimination including elemental diet was performed in all patients. Eleven patients (91.7%) were in remission by initial induction therapy, and 72.7% maintained remission for 36 months. Three patients (14.3%) with UC had familial history, 71.4% had pancolitis-type UC, and 66.7% exhibited disease of moderate severity. Colectomy was performed in 4 patients (21.1%). Eighteen patients (85.7%) were in remission by initial induction therapy; however, only 15.8% maintained remission for 36 months. Anal complication was more prevalent in infantile-onset IBD than in childhood-onset IBD (p = 0.014).
CONCLUSIONS: Among Japanese patients aged <8 years who were diagnosed with IBD, colitis-type disease was more common in CD and pancolitis was more common in UC. As the courses of several patients were severe, identifying primary immunodeficiency appears to be necessary to confirm background disease.

PMID: 32422640 [PubMed – as supplied by publisher]

Trigger-dependent differences determine therapeutic outcome in murine primary hemophagocytic lymphohistiocytosis.

May 19, 2020 By Manish Butte

Trigger-dependent differences determine therapeutic outcome in murine primary hemophagocytic lymphohistiocytosis.

Eur J Immunol. 2020 May 17;:

Authors: Gather R, Aichele P, Goos N, Rohr J, Pircher H, Kögl T, Zeiser R, Hengel H, Schmitt-Gräff A, Weaver C, Ehl S

Abstract
Familial hemophagocytic lymphohistiocytosis (FHL) is a hyperinflammatory syndrome affecting patients with genetic cytotoxicity defects. Perforin-deficient (PKO) mice recapitulate the full clinical picture of FHL after infection with lymphocytic choriomeningitis virus (LCMV). Hyperactivated CD8+ T cells and IFNγ have been identified as the key drivers of FHL and represent targets for therapeutic interventions. However, the response of patients is variable. This could be due to trigger-dependent differences in pathogenesis, which is difficult to address in FHL patients, since the trigger frequently escapes detection. We established an alternative FHL model using intravenous infection of PKO mice with murine cytomegalovirus (MCMV)Smith . PKO mice developed acute FHL after both infections and fulfilled HLH diagnostic criteria accompanied by excessive IFNγ production by disease-inducing T cells, that enrich in the bone marrow. However, direct comparison of the two infection models disclosed trigger-dependence of FHL progression and revealed a higher contribution of CD4 T cells and NK cells to IFNγ production after MCMV infection. Importantly, therapeutic intervention by IFNγ neutralization nor CD8+ T-cell depletion had less benefit in MCMV-triggered FHL compared to LCMV-triggered FHL, likely due to MCMV-induced cytopathology. Thus, the context of the specific triggering viral infection can impact the success of targeted immunotherapeutic HLH control. This article is protected by copyright. All rights reserved.

PMID: 32419134 [PubMed – as supplied by publisher]

Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?

May 19, 2020 By Manish Butte

Autoantibodies against cytokines: phenocopies of primary immunodeficiencies?

Hum Genet. 2020 May 17;:

Authors: Ku CL, Chi CY, von Bernuth H, Doffinger R

Abstract
Anti-cytokine autoantibodies may cause immunodeficiency and have been recently recognized as ‘autoimmune phenocopies of primary immunodeficiencies’ and are found in particular, but not exclusively in adult patients. By blocking the cytokine’s biological function, patients with anti-cytokine autoantibodies may present with a similar clinical phenotype as the related inborn genetic disorders. So far, autoantibodies to interferon (IFN)-γ, GM-CSF, to a group of TH-17 cytokines and to IL-6 have been found to be causative or closely associated with susceptibility to infection. This review compares infectious diseases associated with anti-cytokine autoantibodies with primary immunodeficiencies affecting similar cytokines or related pathways.

PMID: 32419033 [PubMed – as supplied by publisher]

Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction.

May 19, 2020 By Manish Butte

Icon for eLife Sciences Publications, Ltd

Persistent epigenetic memory impedes rescue of the telomeric phenotype in human ICF iPSCs following DNMT3B correction.

Elife. 2019 11 20;8:

Authors: Toubiana S, Gagliardi M, Papa M, Manco R, Tzukerman M, Matarazzo MR, Selig S

Abstract
DNA methyltransferase 3B (DNMT3B) is the major DNMT that methylates mammalian genomes during early development. Mutations in human DNMT3B disrupt genome-wide DNA methylation patterns and result in ICF syndrome type 1 (ICF1). To study whether normal DNA methylation patterns may be restored in ICF1 cells, we corrected DNMT3B mutations in induced pluripotent stem cells from ICF1 patients. Focusing on repetitive regions, we show that in contrast to pericentromeric repeats, which reacquire normal methylation, the majority of subtelomeres acquire only partial DNA methylation and, accordingly, the ICF1 telomeric phenotype persists. Subtelomeres resistant to de novo methylation were characterized by abnormally high H3K4 trimethylation (H3K4me3), and short-term reduction of H3K4me3 by pharmacological intervention partially restored subtelomeric DNA methylation. These findings demonstrate that the abnormal epigenetic landscape established in ICF1 cells restricts the recruitment of DNMT3B, and suggest that rescue of epigenetic diseases with genome-wide disruptions will demand further manipulation beyond mutation correction.

PMID: 31738163 [PubMed – indexed for MEDLINE]

Self-administration of icatibant in acute attacks of Type I hereditary angioedema: A case report and review of hereditary angioedema.

May 19, 2020 By Manish Butte

Self-administration of icatibant in acute attacks of Type I hereditary angioedema: A case report and review of hereditary angioedema.

Dermatol Ther. 2019 11;32(6):e13098

Authors: Piras V, Alves F, Gonçalo M

Abstract
Hereditary angioedema (HAE) is a rare group of genetic disease characterized by non-itchy swelling of subcutaneous and submucosal tissues of the extremities, genitalia, gastrointestinal tract, and upper airways, which can be life threatening. Moreover, unpredictability and recurrence of HAE attacks significantly affect patients’ quality of life. Short- and long-term prophylaxis is used to decrease the severity and frequency of attacks, but during severe or potentially severe acute episodes, treatment with C1-INH replacement or icatibant is mandatory. Icatibant is a selective bradykinin B2 receptor antagonist that has been licensed for self-administration at home, resulting in earlier treatment of the attack and quicker recovery, less emergency admittance with a significant improvement of patients’ quality of life, and decrease of health care costs. The authors present a case of a young woman, affected by Type I HAE, who has been successfully treated with icatibant on demand at home, resulting in reduction of emergency admissions and improvement of quality of life. The authors also review the different types HAE, their clinical aspects, diagnosis, and management.

PMID: 31579975 [PubMed – indexed for MEDLINE]