Manish Butte

Intern Med J. 2023 Apr 24. doi: 10.1111/imj.16104. Online ahead of print.

ABSTRACT

Forty-four of 50 Immunology patients with primary or secondary immunodeficiency receiving intravenous immunoglobulin at a hospital in New South Wales, Australia, were rapidly enrolled in the Subcutaneous Immunoglobulin Program at the onset of the 2020 COVID 19 pandemic. Health and economic outcomes demonstrated that SCIg provides clinical efficacy as evidenced by number of infections and maintenance of IgG levels, whilst also facilitating cost reduction in immunoglobulin maintenance programs. This article is protected by copyright. All rights reserved.

PMID:37092797 | DOI:10.1111/imj.16104

J Clin Immunol. 2023 Apr 21. doi: 10.1007/s10875-023-01472-0. Online ahead of print.

ABSTRACT

Patient registries are a very important and essential tool for investigating rare diseases, as most physicians only see a limited number of cases during their career. Diseases of multi-organ autoimmunity and autoinflammation are especially challenging, as they are characterized by diverse clinical phenotypes and highly variable expressivity. The GAIN consortium (German multi-organ Auto Immunity Network) developed a dataset addressing these challenges. ICD-11, HPO, and ATC codes were incorporated to document various clinical manifestations and medications with a defined terminology. The GAIN dataset comprises detailed information on genetics, phenotypes, medication, and laboratory values. Between November 2019 and July 2022, twelve centers from Europe have registered 419 patients with multi-organ autoimmunity or autoinflammation. The median age at onset of symptoms was 13 years (IQR 3-28) and the median delay from onset to diagnosis was 5 years (IQR 1-14). Of 354 (84.5%) patients who were genetically tested, 248 (59.2%) had a defined monogenetic cause. For 87 (20.8%) patients, no mutation was found and for 19 (4.5%), the result was pending. The most common gene affected was NFkB1 (48, 11.5%), and the second common was CTLA4 (40, 9.5%), both genetic patient groups being fostered by specific research projects within GAIN. The GAIN registry may serve as a valuable resource for research in the inborn error of immunity community by providing a platform for etiological and diagnostic research projects, as well as observational trials on treatment options.

PMID:37084016 | DOI:10.1007/s10875-023-01472-0

Allergy Asthma Clin Immunol. 2023 Apr 20;19(1):32. doi: 10.1186/s13223-023-00776-5.

ABSTRACT

Job’s syndrome, or autosomal dominant hyperimmunoglobulin E syndrome (AD-HIES, STAT3-Dominant Negative), is a rare inborn error of immunity (IEI) with multi-organ involvement and long-life post-infective damage. Longitudinal registries are of primary importance in improving our knowledge of the natural history and management of these rare disorders. This study aimed to describe the natural history of 30 Italian patients with AD-HIES recorded in the Italian network for primary immunodeficiency (IPINet) registry. This study shows the incidence of manifestations present at the time of diagnosis versus those that arose during follow up at a referral center for IEI. The mean time of diagnostic delay was 13.7 years, while the age of disease onset was < 12 months in 66.7% of patients. Respiratory complications, namely bronchiectasis and pneumatoceles, were present at diagnosis in 46.7% and 43.3% of patients, respectively. Antimicrobial prophylaxis resulted in a decrease in the incidence of pneumonia from 76.7% to 46.7%. At the time of diagnosis, skin involvement was present in 93.3% of the patients, including eczema (80.8%) and abscesses (66.7%). At the time of follow-up, under therapy, the prevalence of complications decreased: eczema and skin abscesses reduced to 63.3% and 56.7%, respectively. Antifungal prophylaxis decreased the incidence of mucocutaneous candidiasis from 70% to 56.7%. During the SARS-CoV-2 pandemic, seven patients developed COVID-19. Survival analyses showed that 27 out of 30 patients survived, while three patients died at ages of 28, 39, and 46 years as a consequence of lung bleeding, lymphoma, and sepsis, respectively. Analysis of a cumulative follow-up period of 278.7 patient-years showed that early diagnosis, adequate management at expertise centers for IEI, prophylactic antibiotics, and antifungal therapy improve outcomes and can positively influence the life expectancy of patients.

PMID:37081481 | DOI:10.1186/s13223-023-00776-5

J Investig Allergol Clin Immunol. 2023 Apr;33(2):156-157. doi: 10.18176/jiaci.0893.

NO ABSTRACT

PMID:37071443 | DOI:10.18176/jiaci.0893

J Investig Allergol Clin Immunol. 2023 Apr;33(2):154-155. doi: 10.18176/jiaci.0882.

NO ABSTRACT

PMID:37071442 | DOI:10.18176/jiaci.0882

Med Oncol. 2023 Apr 18;40(5):152. doi: 10.1007/s12032-023-02005-w.

ABSTRACT

Lung cancer is amongst the most pervasive malignancies having high mortality rates. It is broadly grouped into non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). The concept of personalized medicine has overshadowed the conventional chemotherapy given to all patients with lung cancer. The targeted therapy is given to a particular population having specific mutations to help in the better management of lung cancer. The targeting pathways for NSCLC include the epidermal growth factor receptor, vascular endothelial growth factor receptor, MET (Mesenchymal epithelial transition factor) oncogene, Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK). SCLC targeting pathway includes Poly (ADP-ribose) polymerases (PARP) inhibitors, checkpoint kinase 1 (CHK 1) pathway, WEE1 pathway, Ataxia Telangiectasia and Rad3-related (ATR)/Ataxia telangiectasia mutated (ATM), and Delta-like canonical Notch ligand 3 (DLL-Immune checkpoint inhibitors like programmed cell death protein 1 (PD-1)/ programmed death-ligand 1 (PD-L1) inhibitors and Cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) blockade are also utilized in the management of lung cancer. Many of the targeted therapies are still under development and require clinical trials to establish their safety and efficacy. This review summarizes the mechanism of molecular targets and immune-mediated targets, recently approved drugs, and their clinical trials for lung cancer.

PMID:37071269 | DOI:10.1007/s12032-023-02005-w

Braz J Biol. 2023 Apr 17;84:e266898. doi: 10.1590/1519-6984.266898. eCollection 2023.

ABSTRACT

Intestinal parasitic infections (IPIs) are endemic worldwide and more prevalent in countries with unhygienic conditions. The objective of the research was to identify the prevalence of intestinal parasitic infections in rural and urban areas of Quetta, Balochistan and to check their associated risk factors including; age, gender, educational status, sanitary system and any other immunodeficiency. For this instance 204 stool samples were collected from the urban and rural population of Quetta, Balochistan. The participants with positive results for Intestinal Parasitic Infections were interviewed using close-ended questionnaire. From the findings of this study, it has been revealed that prevalence of Intestinal parasitic infections in rural and urban areas was 21%. Males were found more prevalent (66%) as compared to females (34%) due to higher risk of contacting to outer environment. The prevalence was higher in rural areas (23%). The most prevalent intestinal parasite was Entamoeba histolytica (48%). Other prevailing parasites were Hymenolepis nana (26%), Giardia Intestinalis (17%), Trichomonas hominis (5%) and Trichuris trichiura (5%). The majority of patients were having lower socio-economic (52%) and educational status (48%). Educational status of 48% patients was primary or below primary. Most of the participants with positive results did not have hand washing habit (62%) and didn’t have the closed sanitary system (71%). The intestinal parasitic infections were more prevalent among children aged from 1-10 (33%). This may be a result of poor hygiene in children. The study will contribute to lower down the prevalence in the studied areas by the application of different preventive measures in future.

PMID:37075409 | DOI:10.1590/1519-6984.266898

Front Immunol. 2023 Mar 29;14:1156823. doi: 10.3389/fimmu.2023.1156823. eCollection 2023.

ABSTRACT

PURPOSE: Patients with X-linked agammaglobulinemia (XLA) are characterized by humoral impairment and are routinely treated with intravenous immunoglobulin (IVIG). In this study, we aimed to investigate the presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in IVIG preparations harvested globally and evaluate the transfer of SARS-CoV-2 antibodies to the XLA patient.

METHODS: A single-center, prospective cohort study was conducted in the period of November 2020 to November 2022. Clinical and laboratory data, specifically, SARS-CoV-2 spike IgG levels from the serum of 115 IVIG preparations given to 5 XLA patient were collected. Concurrently, SARS-CoV-2 spike IgG levels from the serum of the 5 XLA was collected monthly.

RESULTS: Five XLA patients were evaluated within the study period. All were treated monthly with commercial IVIG preparations. A total of 115 IVIG treatments were given over the study period. The origin country and the date of IVIG harvesting was obtained for 111 (96%) of the treatments. Fifty-four IVIG preparations (49%) were harvested during the COVID-19 pandemic of which 76% were positive (>50AU/mL) for SARS-CoV-2 spike antibodies which were subsequently transmitted to the XLA patients in an approximate 10-fold reduction. SARS-CoV2 spike IgG was first detected in IVIG batches that completed their harvest date by September 2021. Positive products were harvested from origin countries with a documented prevalence over 2,000 per 100,000 population.

CONCLUSION: As the prevalence of COVID-19 infections rises, detection of SARS-CoV-2 spike IgG in commercial IVIG products increases and is then transmitted to the patient. Future studies are needed to investigate the neutralizing capabilities of SARS-CoV-2 IgG and whether titer levels in IVIG remain consistent as the incidence of infection and vaccination rates in the population changes.

PMID:37063907 | PMC:PMC10090293 | DOI:10.3389/fimmu.2023.1156823

Semin Immunol. 2023 Apr 14;67:101761. doi: 10.1016/j.smim.2023.101761. Online ahead of print.

ABSTRACT

Inborn errors of immunity (IEI) are a diverse group of monogenic disorders of the immune system due to germline variants in genes important for the immune response. Over the past decade there has been increasing recognition that acquired somatic variants present in a subset of cells can also lead to immune disorders or ‘phenocopies’ of IEI. Discovery of somatic mosaicism causing IEI has largely arisen from investigation of seemingly sporadic cases of IEI with predominant symptoms of autoinflammation and/or autoimmunity in which germline disease-causing variants are not detected. Disease-causing somatic mosaicism has been identified in genes that also cause germline IEI, such as FAS, and in genes without significant corresponding germline disease, such as UBA1 and TLR8. There are challenges in detecting low-level somatic variants, and it is likely that the extent of the somatic mosaicism causing IEI is largely uncharted. Here we review the field of somatic mosaicism leading to IEI and discuss challenges and methods for somatic variant detection, including diagnostic approaches for molecular diagnoses of patients.

PMID:37062181 | DOI:10.1016/j.smim.2023.101761

BMC Genom Data. 2023 Apr 15;24(1):22. doi: 10.1186/s12863-023-01120-x.

ABSTRACT

BACKGROUND: Previous reports revealed that a history of major depressive disorder (MDD) increased the risk of Alzheimer’s disease (AD). The immune disorder is associated with MDD and AD pathophysiology. We aimed to identify differentially expressed immune-related genes (DEIRGs) that are involved in the pathogenesis of MDD and AD.

METHODS: We downloaded mRNA expression profiles (GSE76826 and GSE5281) from the Gene Expression Omnibus (GEO) database. The R software was used to identify DEIRGs for the two diseases separately. Functional enrichment analysis and PPI network of DEIRGs were performed. Finally, the relationship between shared DEIRGs and immune infiltrates of AD and MDD were analyzed, respectively.

RESULTS: A total of 121 DEIRGs linking AD and MDD were identified. These genes were significantly enriched in immune-related pathways, such as the JAK-STAT signaling pathway, regulation of chemotaxis, chemotaxis, cytokine-cytokine receptor interaction, and primary immunodeficiency. Furthermore, three shared DEIRGs (IL1R1, CHGB, and NRG1) were identified. Correlation analysis between DEIRGs and immune cells revealed that IL1R1 and NRG1 had a negative or positive correlation with some immune cells both in AD and MDD.

CONCLUSION: Both DEIRGs and immune cell infiltrations play a vital role in the pathogenesis of AD and MDD. Our findings indicated that there are common genes and biological processes between MDD and AD, which provides a theoretical basis for the study of the comorbidity of MDD and AD.

PMID:37061663 | DOI:10.1186/s12863-023-01120-x