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Platelets. 2022 Mar 16:1-4. doi: 10.1080/09537104.2022.2053090. Online ahead of print.

ABSTRACT

Autoimmune disorders are common in patients with primary immunodeficiency diseases (PIDs). However, the prevalence of autoimmunity is low in patients with X-linked agammaglobulinemia (XLA), mostly due to the absence of antibodies. Chronic or persistent immune thrombocytopenia (ITP), which is usually considered an antibody-mediated disease, is uncommon in patients with XLA. In this study, we detailly described a surprising autoimmune phenomenon, chronic ITP, in a small boy diagnosed with XLA. This is an interesting phenotype found in XLA, and it is helpful to understand the immune pathogenesis of autoimmunity in patients with XLA.

PMID:35296220 | DOI:10.1080/09537104.2022.2053090

Immunopharmacol Immunotoxicol. 2022 Apr;44(2):147-156. doi: 10.1080/08923973.2021.2023173. Epub 2022 Jan 4.

ABSTRACT

Primary immunodeficiency diseases (PIDs) consist of a heterogeneous group of genetically disorders that affect distinct components of the immune system. They manifest as increased susceptibility to life-threatening infections, as well as autoimmunity and inflammatory disease. Among them, patients with diseases of immune dysregulation and autoinflammatory disorders are more complicated with autoimmunity. On the other hand, tumor necrosis factor alpha (TNF-α) is one of the major players in the pathogenesis of autoimmunity and inflammation in PID patients. Monoclonal antibodies (mAbs) targeting TNF-α would be a potential approach as a therapeutic tool for these diseases. In the current review, we aimed to highlight the characteristics of TNF-α and its important role in the pathogenesis of related complication in PID diseases. Critical evaluation of the mAbs targeting TNF-α (e.g. infliximab, etanercept, and adalimumab) in various immune-mediated complications in PID diseases will be provided, and finally, their clinical efficacy and safety will be reported.

PMID:35296212 | DOI:10.1080/08923973.2021.2023173

Expert Rev Clin Immunol. 2022 Mar 16. doi: 10.1080/1744666X.2022.2054414. Online ahead of print.

ABSTRACT

INTRODUCTION: As the prevalence of food allergies (FA) increases worldwide, our understanding of its pathophysiology and risk factors is markedly expanding. In the past decades, an increasing number of genes have been linked to FA. Identification of such genes may help in predicting the genetic risk for FA development, age of onset, clinical manifestation, causative allergen(s), and possibly the optimal treatment strategies. Furthermore, identification of these genetic factors can help to understand the complex interactions between genes and the environment in predisposition to FA.

AREAS COVERED: We outline the recent important progress in determining genetic variants and disease-associated genes in IgE-mediated FA. We focused on the monogenic inborn errors of immunity (IEI) where FA is one of the clinical manifestations, emphasizing the genes and gene variants which were linked to FA with some of the most robust evidence.

EXPERT OPINION: Genetics play a significant role, either directly or along with environmental factors, in the development of FA. Since FA is a multifactorial disease, it is expected that multiple genes and genetic loci contribute to the risk for its development. Identification of the involved genes should contribute to the area of FA regarding pathogenesis, prediction, recognition, prognosis, prevention, and possibly therapeutic interventions.

PMID:35293838 | DOI:10.1080/1744666X.2022.2054414

Iran J Med Sci. 2022 Mar;47(2):162-166. doi: 10.30476/IJMS.2022.92862.2415.

ABSTRACT

Both adaptive and innate immune responses are essential for an effective defense against the severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the effect of the coronavirus disease 2019 (COVID-19) pandemic on patients with primary immunodeficiency (PID). This study was performed on patients who were diagnosed with PID by immunologist specialists and referred to Imam Reza Clinic of Asthma and Allergy, affiliated with Shiraz University of Medical Sciences, (Shiraz, Iran) for regular check-ups. The patients were enrolled in this cohort study and followed for any sign of COVID-19 from March 2020 to May 2021. COVID-19 infection was confirmed using a real-time polymerase chain reaction (RT-PCR) assay of nasal and pharyngeal swabs. Among the 90 PID patients under study, nine patients (10%) were diagnosed positive for COVID-19 infection. Five out of these nine patients belonged to the combined immunodeficiency (CID) category, while four patients were categorized as having primary antibody deficiencies (PADs). Eight patients with COVID-19 were required to be admitted to the hospital, and three patients died after hospitalization due to COVID-19 infection. It seems that patients with CID are at a higher risk of mortality, due to COVID-19 infection, that other types of PID.

PMID:35291437 | PMC:PMC8919309 | DOI:10.30476/IJMS.2022.92862.2415

Clin Rev Allergy Immunol. 2022 Mar 15. doi: 10.1007/s12016-022-08933-1. Online ahead of print.

ABSTRACT

As the field of inborn errors of immunity expands, providers continually update and fine-tune their diagnostic approach and selection of testing modalities to increase diagnostic accuracy. Here, we first describe a mechanistic consideration of laboratory testing, highlighting both benefits and drawbacks of currently clinically available testing modalities. Next, we provide methods in evaluation of patients presenting with concern for inborn errors of immunity as defined by the International Union of Immunological Societies 2019 phenotypic categories: primary antibody deficiencies, cellular and humoral immune deficiency, disorders of the innate immune system, and syndrome-associated and primary immune regulation disorders (PIRDs). Using the suggested approach in this paper as a roadmap highlights the importance of thorough history taking and physical examination as the foundation to guide further diagnostic tests. This is followed by enumeration and functional testing. Finally, to determine the underlying molecular etiology-specific genetic panels, chromosomal microarrays, and broad genetic testing (whole exome sequencing or whole genome sequencing) are available.

PMID:35290615 | DOI:10.1007/s12016-022-08933-1

J Clin Immunol. 2022 Mar 15. doi: 10.1007/s10875-022-01237-1. Online ahead of print.

ABSTRACT

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency disorder caused by mutations in the Bruton tyrosine kinase (BTK) gene leading to B lymphocyte deficiency and susceptibility to infection. A potential benefit of earlier diagnosis and treatment initiation on morbidity and mortality in XLA is incompletely understood. In the USIDNET Registry, we describe infection frequency and infection-related mortality in patients with XLA and their relationship to age of diagnosis and treatment initiation. Among the 231 XLA patients enrolled in the Registry, respiratory infections (N = 203, 88%) were the most commonly reported. Among those deceased (N = 20) where cause of death was known (N = 17), mortality was attributed to infection in most (N = 12, 71%). Chronic lung disease, often a consequence of repeated lower respiratory tract infection (LRTI), was also a frequent complication associated with mortality (N = 9, 53%). Age of diagnosis in years was lower for those without LRTI compared to those with (median 1.5 [IQR 0.5-3.3] vs. median 3.0 [IQR 1.0-5.0], p = 0.0026) and among living patients compared to deceased (median 1.8 [IQR 0.5-5.0] vs. median 2.7 [IQR 1.6-6.0], p = 0.04). Age at treatment initiation in years was lower among those without LRTIs compared to those with (median 1.0 [IQR 0.4-2.4] vs. median 2.8 [IQR 1.0-5.4], p = 0.0006). For every year increase in age at start of therapy, the odds of experiencing a LRTI was 1.216 (OR 1.216, 95% CI 1.048-1.411, p = 0.01). Given the expected finding of reduced LRTIs and mortality among those with earlier age at diagnosis, our study findings support inclusion of XLA in newborn screening programs.

PMID:35288819 | DOI:10.1007/s10875-022-01237-1

J Clin Immunol. 2022 Mar 14. doi: 10.1007/s10875-022-01240-6. Online ahead of print.

NO ABSTRACT

PMID:35286514 | DOI:10.1007/s10875-022-01240-6

J Clin Immunol. 2022 Mar 14. doi: 10.1007/s10875-022-01222-8. Online ahead of print.

ABSTRACT

PURPOSE: X-linked agammaglobulinemia (XLA) is a primary immunodeficiency (PID) caused by a defect in the gene encoding for Bruton tyrosine kinase (BTK). In the absence of a functional BTK, patients have low or absent circulating B cells and low or absent serum immunoglobulin. Despite gammaglobulin replacement and prompt use of antimicrobial agents, patients with XLA continue to experience infectious and non-infectious complications throughout their lifetime. The purpose of this study was to understand self-perceived health status of US-based patients with XLA, and examine the associations amongst clinical characteristics, treatment experience, and quality of life (QoL).

METHODS: A 46 and 68 question survey, developed by the Immune Deficiency Foundation (IDF) and a Short Form-12item v2® (SF-12v2®) for adults and SF-10™ for children to assess QoL, were mailed by IDF to patients in 2017 and 2018. Those that self-identified as having XLA or males with agammaglobulinemia were selected for analysis. Mean physical and mental composite scores (PCS and MCS) from SF-12v2® and mean physical health component (PHS) and psychological health summary (PSS) from SF-10™ scores were compared to the US normative data.

RESULTS: Ninety-one patients completed the surveys: 58 (63.7%) adults and 33 (36.3%) children. For the combined surveys, the overall median age at time of the survey was 28.5 years (yrs); Inter-Quartile-Range (IQR) 13-49.5 yrs; the median age at diagnosis was 2 yrs (IQR = 0-4 yrs) and the median number of years with XLA diagnosis was 23 (IQR 10.75-40yrs). Amongst adult patients, physical scores were noted to be below the general adult population but did not reach statistical significance. In contrast, 2 or more chronic conditions impacted both physical and mental QoL (p < .001) and hospitalization was associated with significantly decreased physical health QoL (p < .001); three or more infections in the past 12 months exhibited impact on physical health although was not found to be statistically significant. Adult patients with public insurance fared worse in mental health domains compared to those with combined public and private or those with private alone (p = 0.001). Employment status did not impact QoL. None of these variables met statistical significance nor demonstrated impact within the pediatric population in either physical or mental domains of health.

CONCLUSION: Our study provides further insight into what factors impact both physical and mental domains of health amongst patients with XLA. Early detection to prevent the development of associated morbidity, as well as vigilant care to prevent hospitalizations and infections, can limit the impact this disease may have on the overall well-being of XLA patients.

PMID:35284987 | DOI:10.1007/s10875-022-01222-8

Pediatr Hematol Oncol. 2022 Mar 12:1-13. doi: 10.1080/08880018.2022.2045408. Online ahead of print.

ABSTRACT

Primary immune deficiencies are a group of heterogenous genetic disorders characterized by frequent infections, autoimmunity and malignancy. In this study, we aimed to evaluate clinical characteristics, outcomes of children with malignancy developed on background of primary immunodeficiency and compare survival rates of patients between malignant lymphoma with primary immunodeficiency and without immunodeficiency from tertiary oncology center in a developing country. A total 23 patients with primary immunodeficiency and malignancy were evaluated retrospectively. A total of 26 malignancies (first or second) in 23 patients were determined. The median age at the time of the first malignancy was 8 years (ranges 2-18 years) with increased male ratio (M/F:14/9). Non-Hodgkin lymphoma (n = 17; 65%) was the most common malignancy, followed by Hodgkin lymphoma (n = 5), anaplastic ependymoma (n = 1), spinal glioblastoma multiforme (n = 1), retinoblastoma (n = 1) and intracranial hemangiopericytoma (n = 1). The median follow-up time of patients was 25 months (ranges between 1 and 189 months). The 5-year overall survival rate of patients with malignant lymphoma associated with primary immunodeficiency (41%) were lower than immunocompetent patients with malignant lymphoma (80%) (p = 0.000). The 5-year overall survival of patients was diagnosed between 2021 and 2013 years (62%) was higher than previous years (22%) (p = 0.03). In conclusion, non-Hodgkin lymphomas were the most common histopathologic type in patients with malignancy associated with primary immunodeficiency in the present study. The survival of patients with malignant lymphoma associated with primary immunodeficiency has improved in recent years, yet it is still lower than immunocompetent patients with lymphoma and new targeted drugs are required for better survival rates.

PMID:35282762 | DOI:10.1080/08880018.2022.2045408

Front Pediatr. 2022 Feb 28;10:761265. doi: 10.3389/fped.2022.761265. eCollection 2022.

ABSTRACT

All members of the genus Mycobacterium are collectively labeled as “non-tuberculous mycobacterium” (NTM), with the exception of the Mycobacterium tuberculosis complex and M. leprae. Recently, the incidence of NTM infection and number of cases have been increasing, but their identification remains difficult in some countries. Usually, NTM infections and diseases are associated with primary immunodeficiency diseases (PIDs), and their prognoses can be improved with a timely diagnosis and appropriate treatment. Here, we report a case of a 3-year-old boy with disseminated NTM disease (Mycobacterium intracellulare) and interferon-γ receptor 1 (IFNGR1) deficiency. He presented with skin and soft-tissue disease, disseminated osteomyelitis, and pulmonary disease. Initially, we suspected an infection due to the Bacillus Calmette-Guérin vaccine but later suspected Langerhans cell histiocytosis. Following oral treatment of azithromycin, rifampicin, and ethambutol, his condition improved progressively according to clinical and imaging manifestations. This case highlights the importance of early identification of the pathogen in a timely prescription of specific treatments in PIDs patients. We also discuss our experience of treatment of M. intracellulare disease in patients with IFNGR1 deficiency.

PMID:35281241 | PMC:PMC8914208 | DOI:10.3389/fped.2022.761265