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Very early onset inflammatory bowel disease with compound heterozygous variants in Nuclear Factor of Activated T cell 5.

February 10, 2021 By Manish Butte

Very early onset inflammatory bowel disease with compound heterozygous variants in Nuclear Factor of Activated T cell 5.

Eur J Immunol. 2021 Feb 09;:

Authors: Kirk NV, Jensen JMB, Petersen MS, Al-Mousawi A, Mogensen TH, Christiansen M, Larsen CS

PMID: 33559909 [PubMed – as supplied by publisher]

Trough Concentrations of Specific Antibodies in Primary Immunodeficiency Patients Receiving Intravenous Immunoglobulin Replacement Therapy.

February 10, 2021 By Manish Butte

Trough Concentrations of Specific Antibodies in Primary Immunodeficiency Patients Receiving Intravenous Immunoglobulin Replacement Therapy.

J Clin Med. 2021 Feb 04;10(4):

Authors: Hassin O, Abu Freih Y, Hazan R, Lev A, Zrihen KS, Somech R, Broides A, Nahum A

Abstract
Immunoglobulin replacement therapy is a mainstay therapy for patients with primary immunodeficiency (PID). The content of these preparations was studied extensively. Nevertheless, data regarding the effective specific antibodies content (especially in the nadir period), and, in different groups of PID patients is limited. We studied trough IgG concentrations as well as anti-Pneumococcus, anti-Haemophilus influenzae b, anti-Tetanus, and anti-Measles antibody concentrations in 17 PID patients receiving intravenous immunoglobulin (IVIg) compared with healthy controls matched for age and ethnicity. We also analyzed these results according to the specific PID diagnosis: X-linked agammaglobulinemia (XLA), combined immunodeficiency (CID), and ataxia telangiectasia (AT). We recorded a higher concentration of anti-pneumococcal polysaccharide antibodies in healthy controls compared to the entire group of PID patients. We also found significantly higher anti-tetanus toxoid antibody concentrations in the XLA patients, compared to CID patients. Anti-Haemophilus Influenzae b antibody titers were overall similar between all the groups. Interestingly, there were overall low titers of anti-Measles antibodies below protective cutoff antibody concentrations in most patients as well as in healthy controls. We conclude that relying on total IgG trough levels is not necessarily a reflection of effective specific antibodies in the patient’s serum. This is especially relevant to CID patients who may have production of nonspecific antibodies. In such patients, a higher target trough IgG concentration should be considered. Another aspect worth considering is that the use of plasma from adult donors with a waning immunity for certain pathogens probably affects the concentrations of specific antibodies in IVIg preparations.

PMID: 33557365 [PubMed]

IFN-α2a Therapy in Two Patients with Inborn Errors of TLR3 and IRF3 Infected with SARS-CoV-2.

February 10, 2021 By Manish Butte

IFN-α2a Therapy in Two Patients with Inborn Errors of TLR3 and IRF3 Infected with SARS-CoV-2.

J Clin Immunol. 2021 01;41(1):26-27

Authors: Lévy R, Bastard P, Lanternier F, Lecuit M, Zhang SY, Casanova JL

PMID: 33392853 [PubMed – indexed for MEDLINE]

Orthognathic Surgery in Hereditary Angioedema With Normal C1 Inhibitor: A Clinical Response to Concentrated C1 Inhibitor Against Angioedema Attack.

February 10, 2021 By Manish Butte

Orthognathic Surgery in Hereditary Angioedema With Normal C1 Inhibitor: A Clinical Response to Concentrated C1 Inhibitor Against Angioedema Attack.

J Oral Maxillofac Surg. 2021 02;79(2):463-470

Authors: Watanabe T, Yamashita K, Bessho K

Abstract
Hereditary angioedema (HAE) is a rare autosomal dominant disorder characterized by episodes of localized swelling, often of life-threatening severity. HAE due to C1 inhibitor (C1-INH) deficiency is common and is divided into types 1 and 2, but HAE with normal C1-INH is exceedingly rare. Herein, we describe the case of a patient with HAE with normal C1-INH undergoing orthognathic surgery. A 24-year-old woman came to our hospital with a diagnosed jaw deformity and commenced preoperative orthodontic treatment before scheduled orthognathic surgery. During the preoperative period, she experienced mild hoarseness. The hoarseness worsened, and computed tomography revealed mild laryngeal edema. Serum C1-INH, C3, C4, and CH50 levels were normal. Her younger sister had reportedly experienced a similar episode of lip edema previously. These findings supported a diagnosis of HAE with normal C1-INH. She underwent orthognathic surgery in close consultation with a hematologist and anesthesiologist at the age of 33 years. The surgery was completed without complications. She reported throat tightness 4 days after surgery, although her facial swelling was consistent with the procedure performed and was not remarkable. Concentrated C1-INH was administered, and the throat tightness slowly resolved within approximately 1 hour. Twenty-five days after surgery, she was discharged with reduced facial swelling. In the present case, orthognathic surgery was performed successfully in a patient with the exceedingly rare condition of HAE with normal C1-INH, in close consultation with a hematologist and an anesthesiologist. Postoperative throat tightness was successfully treated via the administration of concentrated C1-INH. Concentrated C1-INH administration can be considered in patients with HAE and normal C1-INH who experience angioedemic attack, keeping in mind that it may be slow to take effect.

PMID: 32888936 [PubMed – indexed for MEDLINE]

SARS-COV-2, can you be over it? Arguments for the Immune passport.

February 9, 2021 By Manish Butte

SARS-COV-2, can you be over it? Arguments for the Immune passport.

World Allergy Organ J. 2021 Jan 29;:100514

Authors: Fiocchi A, Jensen-Jarolim E

Abstract
Objectives: Uncertainty has surrounded the duration of immunity against SARS CoV-2. This uncertainty concerns both the duration of vaccine immunity and the duration of natural immunity. We aim to critically review the information available today, and draw practical conclusions.
Methods: This is a narrative review of the recently published information on the topic, compared with the knowledge we already have of the behavior of various viral infectious agents.
Results: It is too early to have any meaningful information on the duration of vaccine immunity against SARS CoV-2. The rate of reinfection is very low. Most of them are due to laboratory errors, to incomplete cure of the primary infection, to the supervening immunodeficiency of the host, or to pre-existing immunodeficiency made evident by the SARS CoV-2 infection. The available studies on the immunology of the infection converge in indicating that it generates a robust and persistent immunity. This behavior does not differ from that of respiratory viruses known to date: in naturally occurring viral respiratory infections, reinfections are exceptional.
Conclusions and implications: The civil community awaits suggestions from scientists not only to protect the lives of susceptible people, but to be able to safely resume activities made uncertain by the pandemic. From the information we have to date, we suggest that in principle, patients who have already overcome the infection should not be prioritized to the SARS CoV-2 vaccine. Instead, they could be provided with an immunological passport that allows them to resume a normal social life.

PMID: 33552379 [PubMed – as supplied by publisher]

Introducing a New Epoch in Inborn Errors of Immunity.

February 9, 2021 By Manish Butte

Introducing a New Epoch in Inborn Errors of Immunity.

J Allergy Clin Immunol Pract. 2021 Feb;9(2):660-662

Authors: Arkwright PD, Walter JE

PMID: 33551040 [PubMed – in process]

SCID newborn screening: What we’ve learned.

February 9, 2021 By Manish Butte

SCID newborn screening: What we’ve learned.

J Allergy Clin Immunol. 2021 Feb;147(2):417-426

Authors: Currier R, Puck JM

Abstract
Newborn screening for severe combined immunodeficiency, the most profound form of primary immune system defects, has long been recognized as a measure that would decrease morbidity and improve outcomes by helping patients avoid devastating infections and receive prompt immune-restoring therapy. The T-cell receptor excision circle test, developed in 2005, proved to be successful in pilot studies starting in the period 2008 to 2010, and by 2019 all states in the United States had adopted versions of it in their public health programs. Introduction of newborn screening for severe combined immunodeficiency, the first immune disorder accepted for population-based screening, has drastically changed the presentation of this disorder while providing important lessons for public health programs, immunologists, and transplanters.

PMID: 33551023 [PubMed – in process]

Bacillus Calmette-Guérin vaccine-related complications in children in Oman.

February 9, 2021 By Manish Butte

Bacillus Calmette-Guérin vaccine-related complications in children in Oman.

Ann Saudi Med. 2021 Jan-Feb;41(1):24-30

Authors: Al Waili B, Al Mufarajii N, Al Hashmi S, Al Ajmi A, Al Sukaiti N

Abstract
BACKGROUND: Bacillus Calmette-Guérin (BCG) vaccine-related complications are frequently observed in children in Oman. There are a few regional studies on BCG complications, but none from Oman.
OBJECTIVE: Evaluate the spectrum of BCG-vaccine related complications and immune status in Omani children.
DESIGN: Retrospective cross-sectional study.
SETTING: Referral tertiary hospital.
METHODS: Children aged younger than 13 years old and with complications of BCG vaccination recorded from 2006-2018 were included in this study. Clinical characteristics, treatment, immune workup and outcome were reviewed from hospital records.
MAIN OUTCOME MEASURES: Different BCG vaccine-related complications categorized by the site of involvement.
SAMPLE SIZE: 226.
RESULTS: Of the 226 children had BCG-vaccine related complications, 99% received BCG vaccine immediately after birth. The median age of presentation was 4 months. The most common complication was isolated BCG lymphadenitis (85%, n=192), followed by BCG-related osteomyelitis (10.2%, n=23) and disseminated BCG infection (4.9%, n=11). The median age of presentation of disseminated BCG was 5 months, with different organs involved. Out of 11 children with disseminated BCG infection, 72.7% (n=8) had primary immune deficiency (PID), including chronic granulomatous disease (CGD, n=5), severe combined immunodeficiency (SCID) (n=2); 1 patient had Mendelian susceptibility to mycobacterial disease (IFNGR2 deficiency); 2 patients with PID not yet identified and the 1 with a non-specific PID had blood or saliva samples sent for whole-exome sequencing.
CONCLUSION: Because of the spectrum of BCG vaccine-related complications, including the most severe in children with PID, we suggest that delaying the BCG vaccine from birth to 6 months may prevent disseminated BCG diseases and their complications in children with PID because any PID will have been identified before 6 months. Further studies are needed to guide this recommendation.
LIMITATIONS: Single center-based study that may not provide a full overview of all BCG vaccine-related complications in Oman. Unavailability of details of some microbiological results and an inability to determine the detailed management for all patients.
CONFLICT OF INTEREST: None.

PMID: 33550906 [PubMed – in process]

Determination of variables for a more accurate diagnostic approach in suspected acute invasive fungal rhinosinusitis: A non-concurrent cohort study.

February 7, 2021 By Manish Butte

Determination of variables for a more accurate diagnostic approach in suspected acute invasive fungal rhinosinusitis: A non-concurrent cohort study.

Clin Otolaryngol. 2021 Feb 06;:

Authors: Lagos AE, García-Huidobro FG, Sepúlveda V, Cruz JP, González C, Callejas CA

Abstract
OBJECTIVE: To describe a group of patients with suspected acute invasive fungal rhinosinusitis (AIFRS) diagnosis, and identify factors associated with a greater risk of presenting this disease.
DESIGN: Non-concurrent cohort study.
SETTING: A single center non-concurrent follow-up of patients with suspected AIFRS between August 2015 and July 2018.
PARTICIPANTS: 50 inpatients referred due to suspected AIFRS at Hospital Clínico Universidad Católica based on the association of a predisposing factor (neutropenia/immunodeficiency/poorly controlled diabetes) with fever of unknown origin.
MAIN OUTCOME MEASURE: The primary outcome was AIFRS diagnosis, defined as a concordant tissue biopsy.
RESULTS: AIFRS was confirmed in 18% (9/50) of the evaluated patients. AIFRS was significantly associated with a positive galactomannan (p=0.04), and a paranasal sinus MRI with lack of contrast enhancement (LoCE) (p=0.04) orbit compromise (p=0.03) or global extrasinusal extension (p=0.04). LoCE and extrasinusal extension in the paranasal sinus/brain MRI were risk factors for AIFRS (OR 16; CI 1.2-210.6 and OR 12.75; CI 1.3-128.8 respectively). Conversely, a nasal endoscopy showing healthy mucosa was identified as a protective factor for AIFRS (OR 0.06; CI 0.007-0.57).
CONCLUSIONS: In patients with suspected AIFRS we identified laboratory and radiologic variables associated with the disease, which may help for a more accurate diagnostic algorithm and approach in this population.

PMID: 33548105 [PubMed – as supplied by publisher]

Immune cartography of macrophage activation syndrome in the COVID-19 era.

February 7, 2021 By Manish Butte

Immune cartography of macrophage activation syndrome in the COVID-19 era.

Nat Rev Rheumatol. 2021 Feb 05;:

Authors: McGonagle D, Ramanan AV, Bridgewood C

Abstract
A hyperinflammatory ‘cytokine storm’ state termed macrophage activation syndrome (MAS), culminating from a complex interplay of genetics, immunodeficiency, infectious triggers and dominant innate immune effector responses, can develop across disparate entities including systemic juvenile idiopathic arthritis (sJIA) and its counterpart adult-onset Still disease (AOSD), connective tissue diseases, sepsis, infection, cancers and cancer immunotherapy. Classifying MAS using the immunological disease continuum model, with strict boundaries that define the limits of innate and adaptive immunity, at one boundary is MAS with loss of immune function, as occurs in the ‘perforinopathies’ and some cases of sJIA-AOSD. Conversely, at the other boundary, immune hypersensitivity with gain of immune function in MHC class II-associated sJIA-AOSD and with chimeric antigen receptor (CAR) T cell therapy also triggers MAS. This provides a benchmark for evaluating severe inflammation in some patients with COVID-19 pneumonia, which cripples primary type I interferon immunity and usually culminates in a lung-centric ‘second wave’ cytokine-driven alveolitis with associated immunothrombosis; this phenomenon is generally distinct from MAS but can share features with the proposed ‘loss of immune function’ MAS variant. This loss and gain of function MAS model offers immune cartography for a novel mechanistic classification of MAS with therapeutic implications.

PMID: 33547426 [PubMed – as supplied by publisher]