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Zhonghua Jie He He Hu Xi Za Zhi. 2023 Feb 12;46(2):158-163. doi: 10.3760/cma.j.cn112147-20220712-00594.

ABSTRACT

A 28-year-old male with a history of leukopenia was admitted with complaints of fever, cough, and dyspnea for 3 months. Initial work-up identified reduced circulating levels of granulocytes, monocytes, lymphocytes, and NK cells. Computed tomography revealed bilateral reticulonodular opacities and mediastinal lymph node enlargement. Peripheral blood culture and mediastinal lymph node aspiration yielded Mycobacterium avium. Genetic testing revealed a heterozygous germline GATA2 mutation (c.1187G>A, R396Q). Despite standard anti-mycobacterial therapy, the patient’s dyspnea worsened and subsequent imaging studies revealed diffuse ground-glass opacification. A transbronchial lung biopsy confirmed the development of pulmonary alveolar proteinosis. Bone marrow transplantation had not been performed due to the unavailability of suitable donors. The disease progressed after whole lung lavage, and the patient died at the age of 31 years from respiratory failure. The current case report emphasized the importance of raising awareness about the rare GATA2 deficiency, which is characterized by hematologic abnormalities, primary immunodeficiency, and pulmonary alveolar proteinosis.

PMID:36740376 | DOI:10.3760/cma.j.cn112147-20220712-00594

Indian J Tuberc. 2023 Jan;70(1):129-133. doi: 10.1016/j.ijtb.2022.04.008. Epub 2022 Apr 30.

ABSTRACT

Mendelian Susceptibility to Mycobacterial Disease describes a spectrum of inherited defects, of which complete deficiency of the interleukin-12 receptor β subunit 1 (IL-12Rβ1) is the most common cause. This condition results in a predisposition to severe disease caused by mycobacteria. We report a case of disseminated multidrug-resistant tuberculosis with extensive central nervous system affection with SARS-CoV-2 co-infection, in a 4-year-old child with IL-12Rβ1 complete deficiency.

PMID:36740310 | DOI:10.1016/j.ijtb.2022.04.008

Clin Exp Med. 2023 Feb 3. doi: 10.1007/s10238-023-01006-3. Online ahead of print.

ABSTRACT

Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by low levels of serum immunoglobulins and increased susceptibility to infections, autoimmune disorders and cancer. CVID embraces a plethora of heterogeneous manifestations linked to complex immune dysregulation. While CVID is thought to be due to genetic defects, the exact cause of this immune disorder is unknown in the large majority of cases. Compelling evidences support a linkage between the gut microbiome and the CVID pathogenesis, therefore a potential for microbiome-based treatments to be a therapeutic pathway for this disorder. Here we discuss the potential of treating CVID patients by developing a gut microbiome-based personalized approach, including diet, prebiotics, probiotics, postbiotics and fecal microbiota transplantation. We also highlight the need for a better understanding of microbiota-host interactions in CVID patients to prime the development of improved preventive strategies and specific therapeutic targets.

PMID:36737487 | DOI:10.1007/s10238-023-01006-3

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