Manish Butte

Case of primary intraocular lymphoproliferative disorder caused by Epstein-Barr Virus.

BMC Ophthalmol. 2020 Jul 28;20(1):306

Authors: Ban Y, Okamoto M, Ogata N

Abstract
BACKGROUND: Cases of panuveitis caused by Epstein-Barr virus (EBV) associated with primary intraocular lymphoproliferative disorder (LPD) are rare in immunocompetent individuals.
CASE PRESENTATION: A 67-year-old man noted blurred vision in both eyes and was referred to our hospital. His best-corrected visual acuity (BCVA) was 20/20 in both eyes. He had mild inflammation in the anterior chamber but not in the vitreous of both eyes. The inflammation was resolved with topical corticosteroid but 10 months later both eyes presented recurrence. Treatment with a sub-Tenon’s injection of steroid was effective for OS but not for OD and 2 months after, the inflammation in the anterior chamber and vitreous opacities got worsen in OD and BCVA decreased to 6/20 OD. Thus, pars plana vitrectomy was performed on OD, and EBV was detected in the aqueous humor by multiplex polymerase chain reaction, and an infiltration of CD19κ positive B cells was revealed in the vitreous specimens by flow cytometry. Systemic workup revealed no other sites of lymphoproliferation, no active EBV infection, or underlying immunodeficiency.
CONCLUSION: Panuveitis caused by EBV associated with primary intraocular LPD can occur in patients with no history of congenital or acquired immunodeficiencies.

PMID: 32723308 [PubMed – as supplied by publisher]

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Global systematic review of primary immunodeficiency registries.

Expert Rev Clin Immunol. 2020 Jul 28;:

Authors: Abolhassani H, Azizi G, Sharifi L, Yazdani R, Mohsenzadegan M, Delavari S, Sohani M, Shirmast P, Chavoshzadeh Z, Mahdaviani SA, Kalantari A, Tavakol M, Jabbari-Azad F, Ahanchian H, Momen T, Sherkat R, Sadeghi-Shabestari M, Aleyasin S, Esmaeilzadeh H, Al-Herz W, Bousfiha AA, Condino-Neto A, Seppänen M, Sullivan KE, Hammarström L, Modell V, Modell F, Quinn J, Orange JS, Aghamohammadi A

Abstract
INTRODUCTION: During the last 4 decades, registration of patients with primary immunodeficiencies (PID) has played an essential role in different aspects of these diseases worldwide including epidemiological indexes, policymaking, quality controls of care/life, facilitation of genetic studies and clinical trials as well as improving our understanding about the natural history of the disease and the immune system function. However, due to the limitation of sustainable resources supporting these registries, inconsistency in diagnostic criteria and lack of molecular diagnosis as well as difficulties in the documentation and designing any universal platform, the global perspective of these diseases remains unclear.
AREAS COVERED: Published and unpublished studies from January 1981 to June 2020 were systematically reviewed on PubMed, Web of Science and Scopus Additionally, the reference list of all studies was hand-searched for additional studies. The authors summarized currently available experiences from different countries regarding the registration of PID patients to more accurately determine the PID prevalence and emphasize better the current burden of these diseases worldwide. This effort identified a total of 104614 registered patients and suggests identification of at least 10590 additional PID patients, mainly from countries located in Asia and Africa. Molecular defects in genes known to cause PID were identified and reported in 13852 (13.2% of all registered) patients.
EXPERT OPINION: Although these data suggest some progress in the identification and documentation of PID patients during the last 40 years worldwide, achieving the basic requirement for the global PID burden estimation and registration of undiagnosed patients will require more reinforcement of the progress, involving both improved diagnostic facilities and neonatal screening.

PMID: 32720819 [PubMed – as supplied by publisher]

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Epidemiology, clinical picture and long-term outcomes of FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia: data from 151 patients.

Am J Hematol. 2020 Jul 28;:

Authors: Rohmer J, Couteau-Chardon A, Trichereau J, Panel K, Gesquiere C, Abdelali RB, Bidet A, Bladé JS, Cayuela JM, Cony-Makhoul P, Cottin V, Delabesse E, Ebbo M, Fain O, Flandrin P, Galicier L, Godon C, Grardel N, Guffroy A, Hamidou M, Hunault M, Lengline E, Lhomme F, Lhermitte L, Machelart I, Mauvieux L, Mohr C, Mozicconacci MJ, Naguib D, Nicolini FE, Rey J, Rousselot P, Tavitian S, Terriou L, Lefèvre G, Preudhomme C, Kahn JE, Groh M, CEREO and GBMHM collaborators

Abstract
FIP1L1-PDGFRA-positive myeloid neoplasm with eosinophilia (F/P+ MN-eo) is a rare disease: robust epidemiological data are lacking and reported issues are scarce, of low sample-size and limited follow-up. Imatinib mesylate (IM) is highly efficient but no predictive factor of relapse after discontinuation has yet been identified. One hundred and fifty-one patients with F/P+ MN-eo (143 males; mean age at diagnosis 49 years; mean annual incidence: 0.18 case per million population) were included in this retrospective nationwide study involving all French laboratories who perform the search of F/P fusion gene (study period: 2003-2019). The main organs involved included the spleen (44%), skin (32%), lungs (30%), heart (19%) and central nervous system (9%). Serum vitamin B12 and tryptase levels were elevated in 74/79 (94%) and 45/57 (79%) patients, respectively, and none of the 31 patients initially treated with corticosteroids achieved complete hematologic remission. All 148 (98%) IM-treated patients achieved complete hematologic and molecular (when tested, n=84) responses. Forty-six patients eventually discontinued IM, among whom 20 (57%) relapsed. In multivariate analysis, time to IM initiation (continuous HR: 1,01 [0.99 – 1,03]; p= 0,05) and duration of IM treatment (continuous HR: 0,97 [0,95-0,99]; p=0,004) were independent factors of relapse after discontinuation of IM. After a mean follow-up of 80 (56) months, the 1, 5- and 10-year overall survival rates in IM-treated patients were 99%, 95% and 84% respectively. In F/P+ MN-eo, prompt initiation of IM and longer treatment durations may prevent relapses after discontinuation of IM. This article is protected by copyright. All rights reserved.

PMID: 32720700 [PubMed – as supplied by publisher]

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Primary Humoral Immune Deficiencies: Overlooked Mimickers of Chronic Immune-Mediated Gastrointestinal Diseases in Adults.

Int J Mol Sci. 2020 Jul 23;21(15):

Authors: Malesza IJ, Malesza M, Krela-Kaźmierczak I, Zielińska A, Souto EB, Dobrowolska A, Eder P

Abstract
In recent years, the incidence of immune-mediated gastrointestinal disorders, including celiac disease (CeD) and inflammatory bowel disease (IBD), is increasingly growing worldwide. This generates a need to elucidate the conditions that may compromise the diagnosis and treatment of such gastrointestinal disorders. It is well established that primary immunodeficiencies (PIDs) exhibit gastrointestinal manifestations and mimic other diseases, including CeD and IBD. PIDs are often considered pediatric ailments, whereas between 25 and 45% of PIDs are diagnosed in adults. The most common PIDs in adults are the selective immunoglobulin A deficiency (SIgAD) and the common variable immunodeficiency (CVID). A trend to autoimmunity occurs, while gastrointestinal disorders are common in both diseases. Besides, the occurrence of CeD and IBD in SIgAD/CVID patients is significantly higher than in the general population. However, some differences concerning diagnostics and management between enteropathy/colitis in PIDs, as compared to idiopathic forms of CeD/IBD, have been described. There is an ongoing discussion whether CeD and IBD in CVID patients should be considered a true CeD and IBD or just CeD-like and IBD-like diseases. This review addresses the current state of the art of the most common primary immunodeficiencies in adults and co-occurring CeD and IBD.

PMID: 32718006 [PubMed – in process]

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Hereditary Angioedema. Reply.

N Engl J Med. 2020 07 23;383(4):e20

Authors: Christiansen SC, Busse PJ

PMID: 32706545 [PubMed – indexed for MEDLINE]

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Disseminated Mycobacterium Avium Infection in a Child with Complete Interferon-γ Receptor 1 Deficiency due to Compound Heterozygosis of IFNGR1 for a Subpolymorphic Copy Number Variation and a Novel Splice-Site Variant.

J Pediatr Genet. 2020 Sep;9(3):186-192

Authors: Bossi G, Errichiello E, Zuffardi O, Marone P, Monzillo V, Barbarini D, Vergori A, Bassi LA, Rispoli GA, De Amici M, Zecca M

Abstract
Complete interferon-γ receptor 1 deficiency is a monogenic primary immunodeficiency caused by IFNGR1 germline defects, with autosomal dominant or recessive inheritance, which results in invasive mycobacterial diseases with varying degrees of severity. Most of the autosomal recessive IFNGR1 mutations are homozygous loss-of-function single-nucleotide variants, whereas large genomic deletions and compound heterozygosity have been very rarely reported. Herein we describe the clinical presentation, diagnosis, and successful treatment with hematopoietic stem cell transplantation of a child with disseminated Mycobacterium avium infection due to compound heterozygosity for a subpolymorphic copy number variation and a novel splice-site variant.

PMID: 32714620 [PubMed]

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Boswellia carteri extract and 3-O-acetyl-alpha-boswellic acid suppress T cell function.

Fitoterapia. 2020 Jul 23;:104694

Authors: Zimmermann-Klemd AM, Reinhardt JK, Nilsu T, Morath A, Falanga CM, Schamel WW, Huber R, Hamburger M, Gründemann C

Abstract
Resins from various Boswellia species have a long track record in different cultures as a treatment for inflammatory diseases. This study was designed to provide evidence for the anti-inflammatory capacity and medicinal use of Boswellia carteri (Burseraceae). A dichloromethane (DCM) extract of B. carteri gum resin and isolated compounds thereof were immunologically characterized. Flow cytometric-based analysis was performed to investigate the impact of B. carteri extract on proliferation, viability, and function of anti-CD3 and anti-CD28 activated human primary T cells. The secretion level of IL-2 and IFN-γ was determined by a bead array-based flow cytometric technique. HPLC-based activity profiling of the B. carteri extract identified active compounds. The impact of B. carteri extract and isolated compounds on the IL-2 transcription factor activity was addressed using specially designed Jurkat reporter cells. The extract of B. carteri suppressed the proliferation of human primary T lymphocytes in vitro in a concentration-dependent manner, without inducing cytotoxicity. Thereby, the B. carteri extract further reduced the degranulation capacity and cytokine secretion of stimulated human T cells. Transcription factor analysis showed that the immunosuppressive effects of the extract are based on specific NFAT-conditioned suppression within T cell signaling. Through HPLC-based activity profiling of the extract, 3-O-acetyl-alpha-boswellic acid was identified as the compound responsible for the NFAT-based mechanism. The recent study presents a scientific base for the immunosuppressive effects of B. carteri gum resin extract including a mode-of-action via the NFAT-conditioned suppression of T lymphocyte proliferation. The immunosuppressive effects of 3-O-acetyl-alpha-boswellic acid are depicted for the first time.

PMID: 32712132 [PubMed – as supplied by publisher]

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An RTEL1 Mutation Links to Infantile-Onset Ulcerative Colitis and Severe Immunodeficiency.

J Clin Immunol. 2020 Jul 24;:

Authors: Ziv A, Werner L, Konnikova L, Awad A, Jeske T, Hastreiter M, Mitsialis V, Stauber T, Wall S, Kotlarz D, Klein C, Snapper SB, Tzfati Y, Weiss B, Somech R, Shouval DS

Abstract
PURPOSE: More than 50 different monogenic disorders causing inflammatory bowel disease (IBD) have been identified. Our goal was to characterize the clinical phenotype, genetic workup, and immunologic alterations in an Ashkenazi Jewish patient that presented during infancy with ulcerative colitis and unique clinical manifestations.
METHODS: Immune workup and whole-exome sequencing were performed, along with Sanger sequencing for confirmation. Next-generation sequencing of the TCRB and IgH was conducted for immune repertoire analysis. Telomere length was evaluated by in-gel hybridization assay. Mass cytometry was performed on patient’s peripheral blood mononuclear cells, and compared with control subjects and patients with UC.
RESULTS: The patient presented in infancy with failure to thrive and dysmorphic features, consistent with a diagnosis of dyskeratosis congenita and Hoyeraal-Hreidarsson syndrome. Severe ulcerative colitis manifested in the first year of life and proceeded to the development of a primary immunodeficiency, presenting as Pneumocystis jiroveci pneumonia and hypogammaglobulinemia. Genetic studies identified a deleterious homozygous C.3791G>A missense mutation in the helicase regulator of telomere elongation 1 (RTEL1), leading to short telomeres in the index patient. Immune repertoire studies showed polyclonal T and B cell receptor distribution, while mass cytometry analysis demonstrated marked immunological alterations, including a predominance of naïve T cells, paucity of B cells, and a decrease in various innate immune subsets.
CONCLUSIONS: RTEL1 mutations are associated with significant alterations in immune landscape and can manifest with infantile-onset IBD. A high index of suspicion is required in Ashkenazi Jewish families where the carriage rate of the C.3791G>A variant is high.

PMID: 32710398 [PubMed – as supplied by publisher]

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