Manish Butte

Correlation of tumor-infiltrating immune cells of melanoma with overall survival by immunogenomic analysis.

Cancer Med. 2020 Sep 15;:

Authors: Huang L, Chen H, Xu Y, Chen J, Liu Z, Xu Q

Abstract
AIMS: Different types of tumor-infiltrating immune cells not only augment but also dampen antitumor immunity in the microenvironment of melanoma. Therefore, it is critical to provide an overview of tumor-infiltrating immune cells in melanoma and explore a novel strategy for immunotherapies.
METHODS: We analyzed the immune states of different stages in melanoma patients by the immune, stromal, and estimation of stromal and immune cells in malignant tumor tissues using expression data (ESTIMATE) scores. Immune cell types were identified by the estimating relative subsets of RNA transcripts (CIBERSORTx) algorithm in 471 melanoma and 324 healthy tissues. Moreover, we performed a gene set variation analysis (GSVA) to determine the differentially regulated pathways in the tumor microenvironment.
RESULTS: In melanoma cohorts, we found that ESTIMATE and immune scores were involved in survival or tumor clinical stage. Among the 22 immune cells, CD8+ T cells, M2 macrophages, and regulatory T cells (Tregs) showed significant differences using the CIBERSORTx algorithm. Furthermore, GSVA identified the immune cell-related pathways; the primary immunodeficiency pathway, intestinal immune network for IgA, and TGF-β pathways were identified as participants of the crosstalk in CD8+ T cells, Tregs, and M2 macrophages in the melanoma microenvironment.
CONCLUSION: These results reveal the cellular and molecular characteristics of immune cells in melanoma, providing a method for selecting targets of immunotherapies and promoting the efficacy of therapies for the treatment of melanoma.

PMID: 32931642 [PubMed – as supplied by publisher]

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Primary intestinal lymphangiectasia diagnosed by video capsule endoscopy in a patient with immunodeficiency presenting with Morganella morganii bacteraemia.

BMJ Case Rep. 2020 Sep 13;13(9):

Authors: Cunningham JM, Nepal S, Truesdale AE

Abstract
A 24-year-old woman with a medical history of chronic lower extremity oedema, abdominal pain, diarrhoea and recurrent pulmonary infections presented with sepsis from right lower extremity cellulitis. Blood cultures grew Morganella morganii Laboratory evaluation revealed lymphopaenia, hypogammaglobulinaemia, a low CD4+ T-cell count and nutritional deficiencies resulting from protein-losing enteropathy (PLE). CT showed small bowel wall thickening in the jejunum and ileum. Primary intestinal lymphangiectasia (PIL) was the likely diagnosis that explained her PLE and immunodeficiencies. Video capsule endoscopy is an important diagnostic tool for distal small bowel pathology and confirmed patchy areas of lymphangiectasia of the jejunum and ileum. Secondary causes of lymphangiectasia were ruled out. Clinically significant immunodeficiency from PIL has not been frequently documented, and this case adds to the literature of rare infections associated with PIL. Treatment with intravenous antibiotics resolved her septicaemia, while dietary modifications improved her oedema, abdominal pain and diarrhoea.

PMID: 32928820 [PubMed – in process]

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Review: Why screen for severe combined immunodeficiency disease?

Arch Pediatr. 2020 Sep 11;:

Authors: Thomas C, Hubert G, Catteau A, Danielo M, Riche VP, Mahlaoui N, Moshous D, Audrain M

Abstract
Newborn screening for severe combined immunodeficiency (SCID) is now routinely performed in many countries across Europe and around the world. The number of T-cell receptor excision circles (TRECs) reflects T cell levels. TREC quantification is possible using dried blood spot (DBS) samples already collected from newborns to screen for other conditions. This method is very sensitive and highly specific. Data in the literature show that the survival rate for children with SCID is much higher when the disease is detected through early screening, as opposed to a later diagnosis. Newborns diagnosed with SCID may receive the appropriate care quickly, before the onset of serious infectious complications, which raises survival rates, improves quality of life, and limits side effects and treatment costs. At the request of the French Ministry of Health, France’s National Authority for Health (Haute Autorité de Santé) is expected to issue recommendations on this topic soon. The nationwide DEPISTREC study, involving 48 maternity units across France, showed that routine SCID screening is feasible and effective. Such screening offers the additional benefit of also diagnosing non-SCID lymphopenia within the infant population.

PMID: 32928653 [PubMed – as supplied by publisher]

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Efficacy and safety of human intravenous immunoglobulin 5% (Ig VENA) in pediatric patients affected by primary immunodeficiency.

Int J Immunopathol Pharmacol. 2020 Jan-Dec;34:2058738420943006

Authors: Ricci S, Lippi F, Canessa C, Guarnieri C, Macchia R, Azzari C

Abstract
Patients affected by primary immunodeficiencies are characterized for high susceptibility for severe infections. Our data demonstrate Kedrion 5% intravenous immunoglobulin G (IVIg) treatment effective and safe as replacement therapy for children and adolescents affected by primary immunodeficiency. The particularities of our study are the selection of a long period of follow-up (71 patient-years of follow-up), and to the best of our knowledge, our study is one of few that assesses the safety and efficacy of intravenous immunoglobulin treatment of primary immunodeficiency specifically in a pediatric population.

PMID: 32924667 [PubMed – as supplied by publisher]

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Nocardiosis Associated with Primary Immunodeficiencies (Nocar-DIP): an International Retrospective Study and Literature Review.

J Clin Immunol. 2020 Sep 12;:

Authors: Lafont E, Marciano BE, Mahlaoui N, Neven B, Bustamante J, Rodriguez-Nava V, Rawat A, Unzaga MJ, Fischer A, Blanche S, Lortholary O, Holland SM, Lebeaux D

Abstract
PURPOSE: Nocardiosis is a life-threatening infectious disease. We aimed at describing nocardiosis in patients with primary immunodeficiency diseases (PID).
METHODS: This international retrospective cohort included patients with PID and nocardiosis diagnosed and/or published from Jan 1, 2000, to Dec 31, 2016. To identify nocardiosis cases, we analyzed PID databases from the French National Reference Center for PID (Paris, France) and the National Institute of Health (NIH, United States of America) and we performed a literature review on PubMed.
RESULTS: Forty-nine cases of nocardiosis associated with PID were included: median age at diagnosis of nocardiosis was 19 (0-56) years and most cases were observed among chronic granulomatous disease (CGD) patients (87.8%). Median time from symptoms to diagnosis of Nocardia infection was 20 (2-257) days. Most frequent clinical nocardiosis presentation was pneumonia (86.7%). Twelve-month mortality rate was 4.2%, and 11.9% of patients experienced a possible recurrence of infection. Nocardiosis more frequently led to the diagnosis of PID among non-CGD patients than in CGD patients. Non-CGD patients experienced more cerebral nocardiosis and more disseminated infections, but mortality and recurrence rates were similar. Highest incidences of nocardiosis among PID cohorts were observed among CGD patients (0.0057 and 0.0044 cases/patient-year in the USA and in France, respectively), followed by IL-12p40 deficiency.
CONCLUSIONS: Among 49 cases of nocardiosis associated with PID, most patients had CGD and lung involvement. Both mortality and recurrence rates were low.

PMID: 32920680 [PubMed – as supplied by publisher]

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Fine-needle aspiration cytology of Bacille Calmette-Guerin adenitis: A perplexing distinct clinical entity.

Diagn Cytopathol. 2020 Sep 12;:

Authors: Jain A, Gupta S, Gupta P, Rohilla M, Gupta N, Srinivasan R, Rajwanshi A, Dey P

Abstract
BACKGROUND: Bacille Calmette-Guerin (BCG) adenitis is a common complication of post-BCG vaccination. Awareness of this lesser known entity in fine-needle aspiration (FNA) is important to prevent misdiagnosis.
AIM: This study described the clinical presentation, cytomorphological features and disease pattern in patients with BCG adenitis.
MATERIALS AND METHODS: We analyzed a series of 15 patients with BCG adenitis seen from July 2017 to July 2019. The detailed clinical and cytomorphology of these cases were studied.
RESULTS: Age of presentation ranged from 3 to 12 months. Male to female ratio was 2.75:1. A total of four children were diagnosed with primary immunodeficiency. Three children had acyanotic heart disease. Most of the children had left axillary lymph node enlargement. Cytomorphology showed the presence of polymorphs (66.7%), histiocytic aggregates (80%) and reactive lymphoid population (60%). Epithelioid granulomas (26.7%) and giant cells (6.7%) were present. The necrotic background was present in all but one case. Ziehl-Neelsen stain for acid-fast bacilli was positive in all but two cases.
CONCLUSION: A high index of clinical suspicion for BCG lymphadenitis should be kept in mind for patients who are recently vaccinated. FNA cytology, combined with clinical correlation, is useful for diagnosis and management.

PMID: 32918799 [PubMed – as supplied by publisher]

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Long-Term Survival after Progressive Multifocal Leukoencephalopathy in a Patient with Primary Immune Deficiency and NFKB1 Mutation.

J Clin Immunol. 2020 Sep 11;:

Authors: Maréchal E, Beel K, Crols R, Hernalsteen D, Willekens B

Abstract
PURPOSE: To describe the development of progressive multifocal leukoencephalopathy (PML) in a patient with primary immune deficiency (PID) due to a NFKB1 (nuclear factor kB subunit 1) mutation, who was treated successfully with a combination of mirtazapine and mefloquine.
METHODS: We’ve based the treatment of our patient on literature research and provide a review of PML in CVID patients.
RESULTS: Only a few reports have been published on the occurrence of PML in PID. PML is mainly observed in patients with reduced cellular immunity, which was not the case in our patient. Successful treatment options in this population are limited. Though severely disabled, our patient still survives, more than 4 years after symptom onset and shows consistent improvement on MRI (magnetic resonance imaging) and CSF (cerebrospinal fluid) analysis.
CONCLUSION: We conclude that some patients with PML might be treatable and can show long-term survival although neurological deficits remain. Involvement of humoral immunity in the pathogenesis of PML as well as the possible role of NFKB1 mutations in response to specific pathogens deserves further investigation.

PMID: 32918165 [PubMed – as supplied by publisher]

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Retained primary teeth in STAT3 hyper-IgE syndrome: early intervention in childhood is essential.

Orphanet J Rare Dis. 2020 Sep 10;15(1):244

Authors: Meixner I, Hagl B, Kröner CI, Spielberger BD, Paschos E, Dückers G, Niehues T, Hesse R, Renner ED

Abstract
BACKGROUND: STAT3 hyper-IgE syndrome (STAT3-HIES) is a rare primary immunodeficiency that clinically overlaps with atopic dermatitis. In addition to eczema, elevated serum-IgE, and recurrent infections, STAT3-HIES patients suffer from characteristic facies, midline defects, and retained primary teeth. To optimize dental management we assessed the development of dentition and the long-term outcomes of dental treatment in 13 molecularly defined STAT3-HIES patients using questionnaires, radiographs, and dental investigations.
RESULTS: Primary tooth eruption was unremarkable in all STAT3-HIES patients evaluated. Primary tooth exfoliation and permanent tooth eruption was delayed in 83% of patients due to unresorbed tooth roots. A complex orthodontic treatment was needed for one patient receiving delayed extraction of primary molars and canines. Permanent teeth erupted spontaneously in all patients receiving primary teeth extraction of retained primary teeth during average physiologic exfoliation time.
CONCLUSIONS: The association of STAT3-HIES with retained primary teeth is important knowledge for dentists and physicians as timely extraction of retained primary teeth prevents dental complications. To enable spontaneous eruption of permanent teeth in children with STAT3-HIES, we recommend extracting retained primary incisors when the patient is not older than 9 years of age and retained primary canines and molars when the patient is not older than 13 years of age, after having confirmed the presence of the permanent successor teeth by radiograph.

PMID: 32912316 [PubMed – in process]

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