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Otolaryngol Head Neck Surg. 2023 Nov 8. doi: 10.1002/ohn.579. Online ahead of print.

ABSTRACT

This is the first study to examine chronic rhinosinusitis (CRS) outcomes after starting immunoglobulin (Ig) replacement therapy for patients with primary (PID) and secondary immunodeficiency (SID). This is a retrospective review of patients diagnosed with CRS from 2018 to 2022 prior to initiating Ig therapy for the treatment of PID or SID. Outcomes included medication use and Sinonasal Outcome Test (SNOT-22) scores. Ten patients met the inclusion criteria. PID and SID patients had a decrease in antibiotics (PID: 9.40 to 3.20, P = .05, SID: 8.20 to 2.00, P = .04) and steroids (PID: (5.40 to 0.60; P = .06; SID: 2.20 to 0.20, P = .047) prescribed in the year after Ig compared to the year prior. Patients with SID had a decrease in mean SNOT-22 scores by 12 months after Ig (47.50 to 20.50, P = 0.03). Patients receiving Ig for PID and SID showed decreased medication use and SID patients experienced subjective improvement in CRS symptoms in year-over-year comparison.

PMID:37937734 | DOI:10.1002/ohn.579

Allergol Immunopathol (Madr). 2023 Nov 1;51(6):45-53. doi: 10.15586/aei.v51i6.927. eCollection 2023.

ABSTRACT

BACKGROUND: The present study aimed to evaluate the quality of life, depression, and anxiety scores of children with primary immunodeficiency (PID) and depression, anxiety scores, and the caregiving burden of their mothers.

METHODS: A total of 149 children aged 2-18 years and their mothers were included in the present study, along with 125 healthy children and their mothers as a control group. The Pediatric Quality of Life Inventory (PedsQL), Child Depression Inventory (CDI), and Screening for Child Anxiety-Related Emotional Disorders (SCARED) questionnaire were used based on the views of children and their mothers. The Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Temperament Evaluation of Memphis, Pisa, Paris, San Diego Autoquestionnaire (TEMPS-A), and Zarit Caregiver Burden Scale (ZCB) were used for the mothers.

RESULTS: According to children and their mothers, the scores of the PedsQL were lower than that of the control group (P < 0.05). In addition, according to the views of children and mothers, we found that PID children had higher depression and anxiety scores than healthy children (P < 0.05). The depression and anxiety levels of mothers in the patient group were also significantly higher than those in the control group (P = 0.05 and P = 0.001).

CONCLUSION: Statistically, we found significantly lower psychosocial health summary scores and total scale score levels from the subclass of PedsQL in the patient group than in the control group. According to the views of both children and mothers, we observed that PID children had higher depression and anxiety scores than healthy children. It was also found that the BDI and BAI values in case of mothers in the patient group were significantly higher than those in the control group.

PMID:37937495 | DOI:10.15586/aei.v51i6.927

Eur Radiol. 2023 Nov 8. doi: 10.1007/s00330-023-10334-7. Online ahead of print.

ABSTRACT

Our objective in this review is to familiarize radiologists with the spectrum of initial and progressive CT manifestations of pulmonary complications observed in adult patients with primary immunodeficiency diseases, including primary antibody deficiency (PAD), hyper-IgE syndrome (HIES), and chronic granulomatous disease (CGD). In patients with PAD, recurrent pulmonary infections may lead to airway remodeling with bronchial wall-thickening, bronchiectasis, mucus-plugging, mosaic perfusion, and expiratory air-trapping. Interstitial lung disease associates pulmonary lymphoid hyperplasia, granulomatous inflammation, and organizing pneumonia and is called granulomatous-lymphocytic interstitial lung disease (GLILD). The CT features of GLILD are solid and semi-solid pulmonary nodules and areas of air space consolidation, reticular opacities, and lymphadenopathy. These features may overlap those of mucosa-associated lymphoid tissue (MALT) lymphoma, justifying biopsies. In patients with HIES, particularly the autosomal dominant type (Job syndrome), recurrent pyogenic infections lead to permanent lung damage. Secondary infections with aspergillus species develop in pre-existing pneumatocele and bronchiectasis areas, leading to chronic airway infection. The complete spectrum of CT pulmonary aspergillosis may be seen including aspergillomas, chronic cavitary pulmonary aspergillosis, allergic bronchopulmonary aspergillosis (ABPA)-like pattern, mixed pattern, and invasive. Patients with CGD present with recurrent bacterial and fungal infections leading to parenchymal scarring, traction bronchiectasis, cicatricial emphysema, airway remodeling, and mosaicism. Invasive aspergillosis, the major cause of mortality, manifests as single or multiple nodules, areas of airspace consolidation that may be complicated by abscess, empyema, or contiguous extension to the pleura or chest wall. CLINICAL RELEVANCE STATEMENT: Awareness of the imaging findings spectrum of pulmonary complications that can occur in adult patients with primary immunodeficiency diseases is important to minimize diagnostic delay and improve patient outcomes. KEY POINTS: • Unexplained bronchiectasis, associated or not with CT findings of obliterative bronchiolitis, should evoke a potential diagnosis of primary autoantibody deficiency. • The CT evidence of various patterns of aspergillosis developed in severe bronchiectasis or pneumatocele in a young adult characterizes the pulmonary complications of hyper-IgE syndrome. • In patients with chronic granulomatous disease, invasive aspergillosis is relatively frequent, often asymptomatic, and sometimes mimicking or associated with non-infectious inflammatory pulmonary lesions.

PMID:37935849 | DOI:10.1007/s00330-023-10334-7

J Allergy Clin Immunol. 2023 Nov 5:S0091-6749(23)01390-8. doi: 10.1016/j.jaci.2023.10.018. Online ahead of print.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEI) with dysregulated JAK/STAT signaling present with variable manifestations of immune dysregulation and infections. Hematopoietic stem cell transplantation (HSCT) is potentially curative, but initially reported outcomes were poor. JAK inhibitors (JAKi) offer a targeted treatment option that may be an alternative or bridge to HSCT. However, data on their current use, treatment efficacy and adverse events (AE) are limited.

OBJECTIVE: We evaluated the current off-label JAKi treatment experience for JAK/STAT IEI among ESID/EBMT-IEWP centers.

METHODS: Multicenter retrospective study on patients with a genetic disorder of hyperactive JAK/STAT signaling, who received JAKi treatment for at least 3 months.

RESULTS: Sixty-nine patients (72% children) were evaluated (45 STAT1-GOF, 21 STAT3-GOF, 1 STAT5B-GOF, 1 SOCS1-LOF, 1 JAK1-GOF). Ruxolitinib was the predominantly prescribed JAKi (80%). Overall, treatment resulted in improvement (partial or complete remission) of clinical symptoms in 87% of STAT1-GOF and in 90% of STAT3-GOF patients. We documented very heterogeneous dosing and monitoring regimens. The response rate and time to response varied across different diseases and manifestations. AE (i.e. infections and weight gain) were frequent (38% of patients), but mild (grade I-II) and transient in most patients. At last follow-up, 52/69 (74%) of patients are still receiving JAKi treatment, while 11 patients eventually underwent HSCT following previous JAKi bridging therapy with a 91% overall survival.

CONCLUSIONS: Our study suggests that JAKi may be highly effective to treat symptomatic JAK/STAT-IEI patients. Prospective studies to define optimal JAKi dosing for the variable clinical presentations and age ranges should be pursued.

PMID:37935260 | DOI:10.1016/j.jaci.2023.10.018

Rev Med Inst Mex Seguro Soc. 2023 Oct 2;61(Suppl 3):S484-S491. doi: 10.5281/zenodo.8319786.

ABSTRACT

INTRODUCTION: Up to 25% of patients with common variable immunodeficiency (CVID) debut with autoimmunity, which is related to the Freiburg classification, which is based on flow cytometry.

OBJECTIVE: to determine the frequency and type of autoimmune diseases and their association with the Freiburg classification in adults with CVID.

METHODS: A cross-sectional, analytical and observational study was carried out with 33 patients belonging to the Primary Immunodeficiency Clinic of a third level hospital, with a diagnosis of CVID. They were divided into 3 phenotypes according to the Freiburg classification.

RESULTS: Of the 33 patients studied, 66.6% presented autoimmune diseases, 19 of them (86.3%) had cytopenia; 42.1% belonged to Freiburg group Ia, 36.8% to Ib and 21% to phenotype II. In 36.6% of the patients, autoimmune cytopenia were the first manifestation of CVID; and up to 70% of them belong to the Freiburg phenotype Ia (p = 0.086). Patients with autoimmune cytopenia had a lower percentage of isotype-switched memory B cells (p = 0.018), no higher percentage of CD21low B cells (p = 0.226).

CONCLUSIONS: Classification by CVID phenotypes allows the identification of the patient’s profile according to the percentage of memory B cells with isotype change, which is useful to intentionally search for non-infectious complications of the disease.

PMID:37935008 | DOI:10.5281/zenodo.8319786

J Clin Immunol. 2023 Nov 7. doi: 10.1007/s10875-023-01593-6. Online ahead of print.

ABSTRACT

BACKGROUND: Bronchiectasis is a major respiratory complication in patients with common variable immunodeficiency (CVID) and is associated with recurrent pulmonary infections. However, it is unclear whether other infections or non-infectious respiratory conditions are related to its development.

OBJECTIVE: To identify respiratory comorbidities associated with bronchiectasis in patients with CVID.

METHODS: A total of 1470 CVID patients enrolled in the USIDNET registry were included in a cross-sectional analysis. The primary outcome of our study was to determine the clinical characteristics and other respiratory conditions associated with respiratory comorbidities and physician-reported bronchiectasis.

RESULTS: One hundred ninety-seven CVID patients were noted to have bronchiectasis (13.4%). Affected patients were significantly older than patients without bronchiectasis (median age 54 years vs. 49 years, p = 0.0004). These patients also had lower serum IgA (13 mg/dL IQR 60 mg/dL vs. 28.4 mg/dL IQR 66 mg/dL, p = 0.000). Notably, chronic rhinosinusitis (OR = 1.69 95%CI 1.05-2.75), sinusitis (OR = 2.06 95%CI 1.38-3.09), pneumonia (OR = 2.70 95%CI 1.88-3.88), COPD (OR = 2.66 95%CI 1.51-4.67), and interstitial lung disease (OR = 2.34 95%CI 1.41-3.91) were independently associated with the development of bronchiectasis in this population.

CONCLUSION: These data suggest that lower and upper respiratory infections, chronic lower airway disease, and interstitial lung diseases are independently associated with bronchiectasis in CVID patients. Further study into predisposing conditions related to the development of bronchiectasis in CVID patients may allow prediction and early intervention strategies to prevent the development of this complication.

PMID:37932514 | DOI:10.1007/s10875-023-01593-6

Rev Esp Enferm Dig. 2023 Nov 6. doi: 10.17235/reed.2023.10032/2023. Online ahead of print.

ABSTRACT

Common Variable Immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency in adults, with non-infectious gastrointestinal involvement present in up to 50% of patients, with the small intestine and colon being the most affected areas. Reports have evaluated the effectiveness of biologic therapy in this scenario. Here, we describe the clinical, endoscopic, and histological findings of a patient who presented a satisfactory response to infliximab.

PMID:37929954 | DOI:10.17235/reed.2023.10032/2023

Heliyon. 2023 Oct 18;9(10):e21158. doi: 10.1016/j.heliyon.2023.e21158. eCollection 2023 Oct.

ABSTRACT

BACKGROUND: At present, the pathogenesis of atherosclerosis has not been fully elucidated, and the diagnosis and treatment face great challenges. Cuproptosis is a novel cell death pattern that might be involved in the development of atherosclerosis. However, no research has reported the correlation between cuproptosis and atherosclerosis.

METHODS: The differential cuproptosis-related genes (CRGs) between atherosclerosis group and control group (A-CRGs) were discovered via differential expression analysis. The correlation analysis, PPI network analysis, GO, KEGG and GSEA analysis were performed to investigate the function of A-CRGs. The differences of biological function between atherosclerosis group and control group were investigated via immune infiltration analysis and GSVA. The LASSO regression, nomogram and machine learning models were constructed to predict atherosclerosis risk. The atherosclerosis molecular subtypes clusters were discovered via unsupervised cluster analysis. Subsequently, we used the above research methods to analyze the differential CRGs between clusters (M-CRGs) and evaluate the molecular subtypes identification performance of M-CRGs. Finally, we verified the diagnostic value for atherosclerosis and role in cuproptosis of these CRGs through the validation set and in vitro experiments.

RESULTS: Five A-CRGs were identified and they were mainly related to the biological function of copper ion metabolism and immune inflammatory response. The diagnostic models and nomogram of atherosclerosis based on 5 A-CRGs indicated that these genes had well diagnostic value. A total of two molecular subtypes clusters were obtained in the atherosclerosis group. There were many differences in biological functions between these two molecular subtypes clusters, such as mitochondrial outer membrane permeabilization and primary immunodeficiency. In addition, 3 M-CRGs were identified in the 2 clusters. Machine learning models and nomogram constructed based on M-CRGs showed that these genes had well molecular subtypes identification efficacy. In the end, the results of in vitro experiment and validation set confirmed the diagnostic value for atherosclerosis and role in cuproptosis of these genes.

CONCLUSION: The cuproptosis may be a potential pathogenesis of atherosclerosis and CRGs may be promising markers for the diagnosis and molecular subtypes identification of atherosclerosis.

PMID:37928399 | PMC:PMC10622704 | DOI:10.1016/j.heliyon.2023.e21158

Ophthalmol Ther. 2023 Nov 4. doi: 10.1007/s40123-023-00839-1. Online ahead of print.

ABSTRACT

INTRODUCTION: This study aims to explore awareness, knowledge, and diagnostic/therapeutic practices in monogenic uveitis (mU) among uveitis experts.

METHODS: This is an explorative, cross-sectional survey study. An anonymous, semi-structured, electronic survey was delivered to uveitis experts from the Autoinflammatory Diseases Alliance (AIDA) Network and International Uveitis Study Group (IUSG). We included respondents answering ≥ 50% of the survey.

RESULTS: Seventy-seven participants rated their knowledge of mU as proficient (3.9%), adequate (15.6%), sufficient (16.9%), or poor (63.6%). When asked about the first mU gene they thought of, 60.4% mentioned NOD2, 3.9% mentioned NLRP3 or MEFV, and 49.4% provided incorrect or no answers. Success rates in clinical scenarios varied from 15.6% to 55.8% and were higher for ophthalmologists working in multidisciplinary teams (p < 0.01). Genetic testing was ordered for suspected mU by 41.6% of physicians. The availability of molecular techniques did not significantly differ based on geography (p > 0.05). The public healthcare system ensured a higher percentage of tests prescribed were obtained by patients compared to private insurances (p < 0.00). In terms of disease-modifying anti-rheumatic drugs (DMARDs), tumor necrosis factor-α inhibitors were the most familiar to uveitis experts. The difficulties with off-label therapy procedures were the primary barrier to DMARDs prescription for patients with mU and correlated inversely with the obtained/prescribed drug ratio for interleukin-1 (p < 0.01) and interleukin-6 (p < 0.01) inhibitors.

CONCLUSIONS: This survey identifies proficiency areas, gaps, and opportunities for targeted improvements in patients care. The comprehensive outputs may inform evidence-based guidelines, empowering clinicians with standardized approaches, and drive an AIDA Network-IUSG unified effort to advance scientific knowledge and clinical practice.

PMID:37924480 | DOI:10.1007/s40123-023-00839-1

Clin Exp Med. 2023 Nov 4. doi: 10.1007/s10238-023-01228-5. Online ahead of print.

ABSTRACT

The hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease originally described as Job syndrome. The fundamental causative variant of the HIES is an autosomal dominant mutation in the signal transducer and activator of transcription 3 (STAT3) gene. It is characterized by recurrent staphylococcal cold skin abscess, sinopulmonary infection, eczema, head and face anomalies, frequent bone fractures, eosinophilia and extremely high serum IgE levels (IgE ≥ 2000 IU/mL). However, multiple other genetic defects are also known as HIES-like disorders. Apart from infectious manifestations, STAT3, DOCK8 and TYK2 gene mutations are associated with various malignancies. The most common malignancies reported in these patients are lymphomas, including Hodgkin’s and non-Hodgkin’s lymphomas (NHL) of B and T cells. This systematic review aimed to investigate the prevalence of malignancies in HIES and the factors associated with malignancy in these patients. In this survey, all articles published until April 1st, 2023, in Scopus, PubMed and Web of Science databases based on three groups of keywords related to HIES syndrome and malignancy were reviewed by three different researchers. Finally, 26 articles were evaluated from which 24 papers were meta-analyzed. In the current study, the demographic information of 1133 patients with HIES, which was mentioned in 24 articles enrolled in the project, was collected, and the information related to patients who had malignancy was analyzed and meta-analyzed. A total of 96 patients out of 1133 studied patients had at least one type of malignancy, the overall prevalence of malignancies reported in the articles was 6.5% (95% confidence interval 4.1-9%), and the total prevalence of malignancy in patients with NHL type and patients with squamous cell carcinoma (SCC) was 2.9% (95% confidence interval 1.7-4.4%) and 2.2% (95% confidence interval 0.3-4.1%), respectively. The results of this study indicated that in 6.5% of cases, HIES was complicated with malignancy, and considering the higher rate of these malignancies in women as well as in DOCK8 mutation sufferers, it is necessary for physicians to be aware of this association and includes malignancy screening in follow-up and periodic examinations of these patients. Indeed, more studies in this field will help to clarify the precise figures and predisposing factors of the relationship between HIES and malignancy.

PMID:37924455 | DOI:10.1007/s10238-023-01228-5