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Enferm Infecc Microbiol Clin (Engl Ed). 2023 Feb 1:S2529-993X(23)00035-7. doi: 10.1016/j.eimce.2022.09.013. Online ahead of print.

ABSTRACT

INTRODUCTION: Campylobacter spp. is the leading cause of bacterial enteritis in industrialized countries, but the literature about its recurrence is scarce. The objective of this study is to analyze a case series of recurrent campylobacteriosis in adult and pediatric patients.

METHODS: During a two-year period, the demographic, clinical and microbiological data were collected retrospectively from patients who met the clinical criteria of recurrent Campylobacter spp. gastroenteritis. Enteropathogens were identified by a multiplex-PCR gastrointestinal pathogens panel. When Campylobacter spp. was detected, the stool sample was cultured in specific medium and tested for antibiotic susceptibility.

RESULTS: Twenty-four (2.03%) out of 1180 patients with Campylobacter spp. positive-PCR met the inclusion criteria. Thirteen patients suffered from underlying diseases, and 11 had no known risk factors but they were all pediatric patients. From the 24 patients were documented 70 episodes. One patient had two episodes of bacteremia. Coinfection/co-detection with other enteropathogens was found in 10 patients being Giardia intestinalis the most frequent. Twelve (22.6%) out of 53 isolates were resistant to macrolides. One patient had two isolates of multi-drug resistant C. coli, only susceptible to gentamicin.

CONCLUSION: The results suggest the presence of underlying diseases in most adult patients with recurrent Campylobacter spp. infections, particularly primary immunodeficiency. Most of the pediatric patients with recurrent campylobacteriosis lack of known risk factors. Concomitant detection with other enteropathogens was common. The resistance to macrolides was much higher as compared with previous reported rates.

PMID:36737370 | DOI:10.1016/j.eimce.2022.09.013

Ann Allergy Asthma Immunol. 2023 Feb 1:S1081-1206(23)00077-7. doi: 10.1016/j.anai.2023.01.025. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical trials of the mRNA COVID-19 vaccines excluded individuals with primary antibody deficiencies.

OBJECTIVE: The aim of this study was to evaluate whether antibody and T-cell responses to mRNA COVID-19 vaccination in patients with Common Variable Immunodeficiency (CVID) and Specific Antibody Deficiency (SAD) were comparable to healthy controls.

METHODS: We measured antibody responses against the S protein and the receptor binding domain (RBD) as well as SARS-CoV2 specific T-cell responses using peripheral blood mononuclear cells (PBMCs) 2-8 weeks after subjects completed the primary 2-dose vaccine series.

RESULTS: 12 patients with CVID, 7 patients with SAD, and 10 controls were included in the study. Individuals with CVID had lower IgG and IgA levels against S protein compared to both individuals with SAD (p= 0.27 and p=0.01, respectively) and as well as to controls (p=0.012 and p=0.004, respectively). The CVID group developed lower IgG titers against the RBD epitope compared to the control group (p=0.014). CVID participants had lower neutralizing titers compared to the control group (p=0.002). All SAD participants developed neutralizing titers. All three of our groups (SAD, CVID, and control) developed antigen-specific CD4+ and CD8+ T-cell responses after vaccination.

CONCLUSION: Our results suggest that patients with CVID may have impaired antibody responses to COVID-19 vaccination but intact T-cell responses, while patients with SAD would be expected to have both intact antibody and T-cell responses to vaccination.

PMID:36736722 | DOI:10.1016/j.anai.2023.01.025

Front Pediatr. 2023 Jan 16;10:1042302. doi: 10.3389/fped.2022.1042302. eCollection 2022.

ABSTRACT

Capping protein regulator and myosin 1 linker 2 (CARMIL2) is necessary for invadopodia formation, cell polarity, lamellipodial assembly, membrane ruffling, acropinocytosis, and collective cell migration. CARMIL2 deficiency is a rare autosomal recessive disease characterized by dysfunction in naïve T-cell activation, proliferation, differentiation, and effector function and insufficient responses in T-cell memory. In this paper, we report a 9-year-old female patient with a novel pathogenic variant in CARMIL2 (c.2063C > G:p.Thr688Arg) who presented with various symptoms of primary immunodeficiencies including recurrent upper and lower respiratory infections, perioral and perineum papules, reddish impetiginized atopic dermatitis, oral ulcer, painful urination and vaginitis, otitis media, and failure to thrive. A missense mutation leading to insufficient CARMIL2 protein expression, reduced absolute T-cell and natural killer cell (NK cell) counts, and marked skewing to the naïve T-cell form was identified and indicated defective maturation of T cells and B cells. Following 1 year of multitargeted treatment with corticosteroids, hydroxychloroquine, mycophenolate mofetil, and thymosin, the patient presented with significant regression in rashes. CD4+ T-cell, CD8+ T-cell, and NK cell counts were significantly improved.

PMID:36727012 | PMC:PMC9884805 | DOI:10.3389/fped.2022.1042302

Rev Med Interne. 2023 Jan 30:S0248-8663(23)00036-X. doi: 10.1016/j.revmed.2023.01.010. Online ahead of print.

ABSTRACT

Hypogammaglobulinemia (hypoγ) is defined as a serum IgG level < 7 g/L. It is most often detected on serum protein electrophoresis. Given the existence of transient hypoγ, its persistence should be checked at distance, preferably by requesting a blood test for IgG, IgA and IgM, which will be needed to characterize a possible primary immune deficiency (PID). In the case of association with a monoclonal component, the first step is to look for a cryoglobulin causing a false hypoγ. Otherwise, the etiological investigation is dictated by the clinical examination. For example, the notion of chronic diarrhea should lead to a search for an enteropathy causing a digestive loss of gammaglobulins (an ambiguous situation because some DIP can be complicated by an enteropathy). In the absence of an obvious explanation, a secondary cause must first be ruled out (secondary immune deficiencies are 30 times more common than PID). The first simple test to perform is 24-hour proteinuria, coupled with urinary protein electrophoresis, to rule out 2 diagnoses: nephrotic syndrome and light chain myeloma. Subsequently, blood immunophenotyping looking for a circulating B clone is recommended, allowing the investigations to be directed towards a lymphoid hemopathy. Drug-induced hypoγ may also be suspected if certain drugs such as corticosteroids, anti-epileptics or immunosuppressive agents (especially anti-CD20) are taken. The profile of a drug-induced hypoγ is different from that of a DIP: it is rarely profound, the IgA level is preserved and there is no deficit in switched memory B lymphocytes. Finally, a thoracoabdominal CT-scan will help to rule out a thymoma and identify a deep tumor syndrome. If all these tests are normal, a PID is suspected, the leader of which in adults remains the common variable immunodeficiency, which is the most frequent symptomatic PID in adults.

PMID:36725480 | DOI:10.1016/j.revmed.2023.01.010

Clin Exp Immunol. 2023 Feb 1:uxad008. doi: 10.1093/cei/uxad008. Online ahead of print.

NO ABSTRACT

PMID:36722341 | DOI:10.1093/cei/uxad008

J Pediatr Gastroenterol Nutr. 2023 Jan 31. doi: 10.1097/MPG.0000000000003714. Online ahead of print.

ABSTRACT

OBJECTIVES: We sought to evaluate the safety and effectiveness of fecal microbiota transplantation (FMT) for recurrent Clostridioides difficile infection (CDI) in pediatric immunocompromised (IC) patients.

METHODS: This is a multi-center retrospective cohort study of pediatric participants who underwent FMT between March 2013 and April 2020 with 12-week follow-up. Pediatric patients were included if they met the definition of IC and were treated with FMT for an indication of recurrent CDI. We excluded patients over 18 years of age, those with incomplete records, insufficient follow up, or not meeting study definition of IC. We also excluded those treated for Clostridioides difficile recurrence without meeting the study definition and those with inflammatory bowel disease without another immunocompromising condition.

RESULTS: Of 59 pediatric patients identified at nine centers, there were 42 who met inclusion and no exclusion criteria. Included patients had a median age of 6.7 years. Etiology of IC included: solid organ transplantation (18, 43%), malignancy (12, 28%), primary immunodeficiency (10, 24%), or other chronic conditions (2, 5%). Success rate was 79% after first FMT and 86% after one or more FMT. There were no statistically significant differences in patient characteristics or procedural components when patients with a failed FMT were compared to those with a successful FMT. There were 15 total serious adverse events (SAEs) in 13 out of 42 (31%) patients that occurred during the follow-up period; four (9.5%) of which were likely treatment-related. There were no deaths or infections with multi-drug resistant organisms during follow-up and all patients with a serious adverse event fully recovered.

CONCLUSIONS: The success rate of FMT for recurrent CDI in this pediatric IC cohort is high and mirrors data for IC adults and immunocompetent children. FMT-related SAEs do occur (9.5%) and highlight the need for careful consideration of risk and benefit.

PMID:36720105 | DOI:10.1097/MPG.0000000000003714

Vox Sang. 2023 Jan 30. doi: 10.1111/vox.13404. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Immunoglobulin (Ig) usage has ongoing shortage concerns. Secondary immunodeficiencies (SIDs) account for a major proportion of usage of Igs in Canada. We audited Ig usage in patients with SID at three British Columbia hospitals to determine whether more stringent local guidelines are necessary.

MATERIALS AND METHODS: A retrospective chart review was performed for patients who had Ig ordered between 1 January 2018 and 31 December 2019 for any SID indication. Cohorts were stratified into chronic and new users, and the Australian BloodSTAR guidelines were used as the benchmark at the time of conception. Having an eligible primary diagnosis, meeting SID criteria, an appropriate dosage and follow-up immunoglobulin G (IgG) levels encompassed appropriate usage.

RESULTS: There were no demographic differences between chronic (N = 81) and new (N = 33) cohorts. The new cohort had a higher rate of appropriate usage (45.7% vs. 66.7%, p = 0.06). The most common reason for inappropriate usage in both groups was the lack of follow-up IgG level at 6 or 12 months. Factors, displayed by relative risk (RR), associated with appropriateness included the dispensing hospital (RR: 6.60), use of subcutaneous Ig (RR: 3.84), having an IgG level before starting therapy (RR: 3.51) and documentation of clinical benefit (RR: 4.70).

CONCLUSION: There are high rates of inappropriate Ig usage in SID patients in both new and chronically treated groups. More stringent local guidelines and processes for assessing initial and ongoing Ig replacement are warranted.

PMID:36717380 | DOI:10.1111/vox.13404

Front Immunol. 2023 Jan 12;13:1062261. doi: 10.3389/fimmu.2022.1062261. eCollection 2022.

ABSTRACT

Wiskott-Aldrich syndrome (WAS) is a rare primary immunodeficiency disease with a predisposition towards autoimmunity and lymphoproliferative diseases. Non-Hodgkin lymphoma (NHL) is reported to be the predominant form of malignant tumor in WAS sufferers. Diffuse large B-cell lymphoma (DLBCL) is one of the most common types of NHL while it is uncommon to occur in paranasal sinuses and especially when associated with WAS. In this article, we report a unique case of WAS associated with DLBCL in paranasal sinuses and review the major publications of WAS-related lymphomas that occurred in the head and neck area. This study extends the available therapies for WAS-related lymphomas and emphasizes the significance of recognition for sinonasal lymphomas in WAS patients presenting with sinusitis.

PMID:36713385 | PMC:PMC9877327 | DOI:10.3389/fimmu.2022.1062261

Mol Biotechnol. 2023 Jan 29. doi: 10.1007/s12033-023-00670-w. Online ahead of print.

ABSTRACT

Varicella zoster virus (VZV) infection causes severe disease such as chickenpox, shingles, and postherpetic neuralgia, often leading to disability. Reactivation of latent VZV is associated with a decrease in specific cellular immunity in the elderly and in patients with immunodeficiency. However, due to the limited efficacy of existing therapy and the emergence of antiviral resistance, it has become necessary to develop new and effective antiviral drugs for the treatment of diseases caused by VZV, particularly in the setting of opportunistic infections. The goal of this work is to identify potent oxazole derivatives as anti-VZV agents by machine learning, followed by their synthesis and experimental validation. Predictive QSAR models were developed using the Online Chemical Modeling Environment (OCHEM). Data on compounds exhibiting antiviral activity were collected from the ChEMBL and uploaded in the OCHEM database. The predictive ability of the models was tested by cross-validation, giving coefficient of determination q² = 0.87-0.9. The validation of the models using an external test set proves that the models can be used to predict the antiviral activity of newly designed and known compounds with reasonable accuracy within the applicability domain (q² = 0.83-0.84). The models were applied to screen a virtual chemical library with expected activity of compounds against VZV. The 7 most promising oxazole derivatives were identified, synthesized, and tested. Two of them showed activity against the VZV Ellen strain upon primary in vitro antiviral screening. The synthesized compounds may represent an interesting starting point for further development of the oxazole derivatives against VZV. The developed models are available online at OCHEM http://ochem.eu/article/145978 and can be used to virtually screen for potential compounds with anti-VZV activity.

PMID:36709460 | DOI:10.1007/s12033-023-00670-w

Curr Top Dev Biol. 2023;152:1-30. doi: 10.1016/bs.ctdb.2022.10.001. Epub 2022 Nov 14.

ABSTRACT

Birth defects are relatively common congenital outcomes that significantly impact affected individuals, their families, and communities. Effective development and deployment of prevention and therapeutic strategies for these conditions requires sufficient understanding of etiology, including underlying genetic and environmental causes. Tremendous progress has been made in defining the genetic basis of familial and syndromic forms of birth defects. However, the majority of birth defect cases are considered nonsyndromic and thought to result from multifactorial gene-environment interactions. While substantial advances have been made in elucidating the genetic landscape of these etiologically complex conditions, significant biological and technical constraints have stymied progress toward a refined knowledge of environmental risk factors. Defining specific gene-environment interactions in birth defect etiology is even more challenging. However, progress has been made, including demonstration of critical proofs of concept and development of new conceptual and technical approaches for resolving complex gene-environment interactions. In this review, we discuss current views of multifactorial birth defect etiology, comparing them with other diseases that also involve gene-environment interactions, including primary immunodeficiency and cancer. We describe how various model systems have illuminated mechanisms of multifactorial etiology and these models’ individual strengths and weaknesses. Finally, suggestions for areas of future emphasis are proposed.

PMID:36707208 | DOI:10.1016/bs.ctdb.2022.10.001