Manish Butte

BMC Endocr Disord. 2022 Nov 12;22(1):278. doi: 10.1186/s12902-022-01150-z.

ABSTRACT

BACKGROUND: 22q11.2 deletion syndrome (DiGeorge syndrome) is associated with multiple organ dysfunctions such as cardiac defects, immunodeficiency, and hypoplasia of parathyroid glands. Moreover, the phenotype of 22q11.2 DS has clinical variability and heterogeneity.

CASE PRESENTATION: In this report, we present the case of a 35-year-old patient with a past medical history that included recurrent infections, mild learning difficulties in childhood, pediatric obesity, and cataract. He was admitted to the endocrinology department for the management of hypogonadism and hypocalcemia. During the 3-year follow-up, the patient gradually developed primary hypoparathyroidism, hypogonadism, chronic renal failure, and heart failure, and his medical condition deteriorated. Meanwhile, in order to improve clinicians’ awareness of the endocrine manifestations of adult 22q11.2 DS and reduce missed diagnoses, we reviewed 28 case reports of adult 22q11.2 DS to analyze the clinical characteristics.

DISCUSSION: Here, we report the case of a young man diagnosed with 22q11.2 DS presented a rare combination of multiple endocrine disorders. This is the first time that a patient with 22q11.2DS had late-onset hypogonadism caused by primary testicular failure combined with decreased pituitary gonadotropin reserve in a patient with 22q11.2DS.

PMID:36371175 | DOI:10.1186/s12902-022-01150-z

Cells. 2022 Oct 24;11(21):3353. doi: 10.3390/cells11213353.

ABSTRACT

B cells and antibodies are indispensable for host immunity. Our understanding of the mechanistic processes that underpin how B cells operate has left an indelible mark on the field of clinical pathology, and recently has also dramatically reshaped the therapeutic landscape of diseases that were once considered incurable. Evaluating patients with primary immunodeficiency diseases (PID)/inborn errors of immunity (IEI) that primarily affect B cells, offers us an opportunity to further our understanding of how B cells develop, mature, function and, in certain instances, cause further disease. In this review we provide a brief compendium of IEI that principally affect B cells at defined stages of their developmental pathway, and also attempt to offer some educated viewpoints on how the management of these disorders could evolve over the years.

PMID:36359748 | DOI:10.3390/cells11213353

Vet Sci. 2022 Nov 8;9(11):618. doi: 10.3390/vetsci9110618.

ABSTRACT

Feline immunodeficiency virus (FIV) is a retrovirus that can cause immunosuppression, co-morbidities, and neoplasia in infected cats, and is commonly tested for in veterinary clinics and animal shelters in Australia. FIV diagnosis using point-of-care (PoC) kits to detect FIV antibodies in Australia is complicated by the commercial availability of an inactivated whole-FIV vaccine. The aim of this study was to determine the accuracy of the RapidSTATUS™ FIV antibody test kit in FIV-vaccinated and FIV-unvaccinated cats in Australia. Plasma from pet cats of known FIV vaccination and FIV infection statuses (n = 361), comprised of 57 FIV-uninfected cats annually vaccinated against FIV, 10 FIV-uninfected cats with lapsed FIV vaccination histories, 259 FIV-unvaccinated/FIV-uninfected cats, and 35 FIV-infected cats, was tested. RapidSTATUS™ FIV testing had sensitivity of 97.1% (34/35) and specificity of 100% (326/326), with an overall accuracy of 99.7% (360/361). Additional testing was undertaken using plasma from FIV-uninfected cats recently administered a primary FIV vaccination course (n = 12) or an annual booster FIV vaccination (n = 10). RapidSTATUS™ FIV was 98.8% (81/82) accurate and 100% (32/32) accurate in cats recently administered primary or annual FIV vaccinations, respectively. The high level of accuracy of RapidSTATUS™ FIV (98.8-100%) therefore establishes this PoC kit as a DIVA (differentiating infected from vaccinated animals) test. RapidSTATUS™ FIV is recommended to aid animal shelters, veterinarians, and researchers in Australia to accurately determine FIV infection status, irrespective of FIV vaccination history.

PMID:36356095 | DOI:10.3390/vetsci9110618

Vet Sci. 2022 Oct 31;9(11):605. doi: 10.3390/vetsci9110605.

ABSTRACT

This article aims to present several interesting and less typical courses of Rhodococcus equi infections in foals, collected during the 2019-2021 foaling seasons in some Polish studs. The study was conducted by the Division of Veterinary Epidemiology and Economics, Warsaw University of Life Sciences-SGGW, and concentrated on ultrasonographic contribution to diagnostics and treatment of the disease. Among many standard cases of rhodococcal pneumonia, some rare ones occurred. The aforementioned issues include the potential contribution of rhodococcal infection to a grave outcome in a prematurely born filly, lost as a yearling, so-called “extrapulmonary disorders” (EPD), a hypothesis of inherited immunodeficiency with grave outcome in a breeding dam line from one stud, and macrolide-induced anhidrosis. The main benefit of this report would be to supplement the general picture of clinical rhodococcosis.

PMID:36356082 | DOI:10.3390/vetsci9110605

Int Forum Allergy Rhinol. 2022 Nov 10. doi: 10.1002/alr.23106. Online ahead of print.

ABSTRACT

BACKGROUND: Primary immunodeficiency disorders (PIDD) may be a risk factor for development of Recurrent Acute Rhinosinusitis (RARS). There are currently no clear guidelines for the timing and methodology of PIDD testing in patients with RARS. The aim of this scoping review is to identify and analyze existing literature on this topic.

METHODS: A scoping review was conducted according to PRISMA-ScR guidelines. Articles addressing recurrent acute sinusitis and immunodeficiencies were collected from PubMed, Web of Science and CINAHL and systematically evaluated for eligibility by two reviewers.

RESULTS: Of the 209 unique articles identified, eleven met criteria for review and analysis. Articles consisted of historical cohort, case control, and cross sectional studies, in addition to case series and non-systematic reviews. The majority (10) recommended immunodeficiency testing, consisting of general immunologic screening (3), quantitative immunoglobulins (6) and post-vaccination antibody titers (5). There was an emphasis on IgG subclass testing (6). Of the eight articles providing timing recommendations, the majority recommended testing after recurrent infections or diagnosis (6); however, criteria for diagnosis of RARS and populations targeted by recommendations varied greatly by article.

CONCLUSIONS: Current literature on RARS emphasizes immunoglobulin quantification and post-vaccination antibody titers to evaluate for PIDD after diagnosis, but recommendations are limited by wide-ranging populations of interest and inconsistent definitions. This scoping review identified a lack of evidence-based articles specific to diagnostic workup for PIDD in patients with RARS, and additional research with standardized definitions and focus on RARS is necessary to guide clinical practice. This article is protected by copyright. All rights reserved.

PMID:36355381 | DOI:10.1002/alr.23106

Pharmacology. 2022 Nov 8:1-8. doi: 10.1159/000527655. Online ahead of print.

ABSTRACT

BACKGROUND: Intravenous immunoglobulin and subcutaneous immunoglobulin preparations are used to treat primary and secondary immunodeficiencies, as well as autoimmune and inflammatory conditions.

SUMMARY: For certain indications, only defined formulations or routes of administration are approved by health authorities. However, for other diseases, there are more options, and treatment decisions may be based on different aspects, such as patient conditions and preferences, pharmacokinetics, or pharmacoeconomic considerations.

KEY MESSAGES: Understanding the two different treatment modalities may support the decision-making for the optimal therapeutic option for individual patients. This review summarizes the latest insights into the direct and indirect comparison between the two types of products.

PMID:36349790 | DOI:10.1159/000527655

Cureus. 2022 Oct 5;14(10):e29931. doi: 10.7759/cureus.29931. eCollection 2022 Oct.

ABSTRACT

Immunoglobulin M (IgM) plays a regulatory role in subsequent immune response development, thereby accelerating the production of immunoglobulin G (IgG) with high affinity. Selective IgM deficiency (SIGMD) is a rare immune disorder that has been reported in association with serious infections, such as bacteremia. Patients commonly present with infections, atopy, septicemia, splenomegaly, neoplasia, and other autoimmune disorders. Treatment modalities and recommendations range from careful monitoring to vaccinations, aggressive management of respiratory infections, preventive and therapeutic antibiotics, and intravenous immunoglobulin (IVIG). There is insufficient information to generalize patients’ prognosis with selective IgM deficiency due to the small number of patients and lack of prospective studies. We hereby present the case of a 28-year-old male with multiple recurrent boils, cellulitis, and osteomyelitis who has been diagnosed with selective IgM deficiency and is being treated with IVIG. This case report highlights the diagnostic evaluation and therapeutic care of patients with SIGMD and the need for follow-up.

PMID:36348833 | PMC:PMC9634333 | DOI:10.7759/cureus.29931

Virol J. 2022 Nov 8;19(1):179. doi: 10.1186/s12985-022-01915-x.

ABSTRACT

We report the case of a girl with congenital thymic dysplasia and refractory disseminated Human Cytomegalovirus (CMV) infection diagnosed by autopsy. Additionally, she was diagnosed with T-cell lymphopenia immunodeficiency and received antiviral therapy with ganciclovir (GCV) /valganciclovir (V-GCV) and enhanced foscarnet. The CMV viral load (VL) monitoring was elevated with retinitis, interstitial pneumonia, and hepatitis. The phenotype of T-cell lymphopenia was uncertain, which limited any alternative therapy by whole-exome sequencing (WES) and lymphocyte subset panel until autopsy. The girl died of progressive respiratory failure and septic shock at ten months of age. Severe disseminated CMV infection typically develops in infants with primary maternal infections and occurs earlier during gestation and in people with a weakened host immune system. Individuals with CMV infection with initial immunodeficiency are associated with a poor prognosis, which is similar to patients with secondary immunodeficiency. This case describes the difficult treatment and prognosis of CMV infection in patients with congenital immunodeficiency, highlighting the importance of early aggressive anti-CMV antiviral therapy in immunodeficiencies, VL monitoring, drug resistance and the role of T-cells in CMV infection.

PMID:36348432 | DOI:10.1186/s12985-022-01915-x

Expert Rev Clin Immunol. 2022 Nov 8. doi: 10.1080/1744666X.2023.2144836. Online ahead of print.

ABSTRACT

INTRODUCTION: Human immunoglobulin (IG) administered intravenously (IVIG) or subcutaneously (SCIG) is used to prevent infections in patients with primary immunodeficiency diseases (PIDDs) such as primary antibody immunodeficiencies.

AREAS COVERED: This review provides an overview of PIDD with a focus on SCIG treatment, including the properties and clinical trial results of a new SCIG 16.5 % (Cutaquig, Octapharma) in pediatric patients. We also discuss the various benefits of SCIG including stable serum immunoglobulin G levels, high tolerability with fewer systemic side effects, and the flexibility of self-administration.

EXPERT OPINION: Individualized treatment for PIDD in children is necessary given the different factors that affect administration of SCIG. Variables such as the dose, dosing interval, administration sites, and ancillary equipment can be adjusted to impact the long-term satisfaction with SCIG administration in pediatric patients. The successful work that has been conducted by both professional and patient organizations to increase awareness of PIDD, especially in pediatric patients, is substantial and ongoing. The importance of early diagnosis and treatment in the pediatric patient population cannot be overstated. The safety, efficacy, and tolerability of SCIG 16.5% have been demonstrated in pediatric patients with PIDDs providing an additional therapeutic option in this vulnerable population.

PMID:36346032 | DOI:10.1080/1744666X.2023.2144836

JCI Insight. 2022 Nov 8;7(21):e154948. doi: 10.1172/jci.insight.154948.

ABSTRACT

Human NK cell deficiency (NKD) is a primary immunodeficiency in which the main clinically relevant immunological defect involves missing or dysfunctional NK cells. Here, we describe a familial NKD case in which 2 siblings had a substantive NKD and neutropenia in the absence of other immune system abnormalities. Exome sequencing identified compound heterozygous variants in Go-Ichi-Ni-San (GINS) complex subunit 4 (GINS4, also known as SLD5), an essential component of the human replicative helicase, which we demonstrate to have a damaging impact upon the expression and assembly of the GINS complex. Cells derived from affected individuals and a GINS4-knockdown cell line demonstrate delayed cell cycle progression, without signs of improper DNA synthesis or increased replication stress. By modeling partial GINS4 depletion in differentiating NK cells in vitro, we demonstrate the causal relationship between the genotype and the NK cell phenotype, as well as a cell-intrinsic defect in NK cell development. Thus, biallelic partial loss-of-function mutations in GINS4 define a potentially novel disease-causing gene underlying NKD with neutropenia. Together with the previously described mutations in other helicase genes causing NKD, and with the mild defects observed in other human cells, these variants underscore the importance of this pathway in NK cell biology.

PMID:36345943 | DOI:10.1172/jci.insight.154948