Indian J Hematol Blood Transfus. 2021 Jul;37(3):511-513. doi: 10.1007/s12288-020-01381-x. Epub 2020 Nov 12.
NO ABSTRACT
PMID:34267479 | PMC:PMC8239097 | DOI:10.1007/s12288-020-01381-x
Powered by WPeMatico
Stanford Alliance for Primary Immunodeficiency
Stanford University
By Manish Butte
Indian J Hematol Blood Transfus. 2021 Jul;37(3):511-513. doi: 10.1007/s12288-020-01381-x. Epub 2020 Nov 12.
NO ABSTRACT
PMID:34267479 | PMC:PMC8239097 | DOI:10.1007/s12288-020-01381-x
Powered by WPeMatico
By Manish Butte
Zhongguo Dang Dai Er Ke Za Zhi. 2021 Jul;23(7):743-748.
ABSTRACT
Gene editing is an advanced technique based on artificial nucleases and can precisely modify genome sequences. It has shown great application prospects in the field of medicine and has provided a new precision therapy for diseases. Primary immunodeficiency disease is a group of diseases caused by single gene mutation and characterized by recurrent and refractory infections, with an extremely high mortality rate. The application of gene editing has brought hope for curing these diseases. This article reviews the development of gene editing technology and briefly introduces the research and application of gene editing technology in primary immunodeficiency disease.
PMID:34266535
Powered by WPeMatico
By Manish Butte
Pediatr Pulmonol. 2021 Jul 15. doi: 10.1002/ppul.25553. Online ahead of print.
ABSTRACT
BACKGROUND: Noncystic fibrosis bronchiectasis (NCFB) is still considered an “orphan disease” in pediatric age.
OBJECTIVE: The study describes the clinical and functional features, the instrumental, and microbial findings of a large cohort of patients with NCFB, followed in a single tertiary level hospital.
METHODS: Children and adolescents diagnosed with NCFB from January 1, 2010 to December 31, 2019 were included. Data from the diagnosis and during the years of follow-up were recorded retrospectively.
RESULTS: One hundred and thirty-eight patients were enrolled. The most common cause of NCFB was postinfectious (33%), followed by primary ciliary dyskinesia (PCD) (30%), esophageal atresia (EA) (9.5%), and secondary immunodeficiency (9.5%). Chronic cough was the most frequent symptom. The median age of symptoms presentation was 3 years (interquartile age [IQR]: 12-84), with a precocious onset in PCD and EA groups. The median age of CT diagnosis was 9 years for all groups but PCD patients who were diagnosed at older age. Lingula, medium, upper, and lower lobes were more involved in PCD group, while diffuse distribution was observed in the postinfectious one. Microbial exams showed Pseudomonas aeruginosa colonization higher in PCD patients (22%). Despite microbial differences in airways colonization, no difference in respiratory exacerbation rate was recorded among groups. Lung function tests demonstrated the stability of forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) over time, except for the secondary immunodeficiency group.
CONCLUSIONS: The role of infections in developed countries should not be underestimated and a major effort to obtain an earlier identification of bronchiectasis should be taken. A prompt diagnosis of NFCB could help to reduce the frequency of exacerbations and improve the stability of lung function over time.
PMID:34265867 | DOI:10.1002/ppul.25553
Powered by WPeMatico
By Manish Butte
Proc Natl Acad Sci U S A. 2021 Jul 20;118(29):e2108082118. doi: 10.1073/pnas.2108082118.
ABSTRACT
Lymphoid tissue inducer (LTi) cells are critical for inducing the differentiation of most secondary lymphoid organs (SLOs) in mice. In humans, JAK3 and γc deficiencies result in severe combined immunodeficiency (SCIDs) characterized by an absence of T cells, natural killer cells, innate lymphoid cells (ILCs), and presumably LTi cells. Some of these patients have undergone allogeneic stem cell transplantation (HSCT) in the absence of myeloablation, which leads to donor T cell engraftment, while other leukocyte subsets are of host origin. By using MRI to look for SLOs in nine of these patients 16 to 44 y after HSCT, we discovered that SLOs were exclusively found in the three areas of the abdomen that drain the intestinal tract. A postmortem examination of a child with γc-SCID who had died 3.5 mo after HSCT showed corticomedullary differentiation in the thymus, T cell zones in the spleen, and the appendix, but in neither lymph nodes nor Peyer patches. Tertiary lymphoid organs were observed in the lung. No RAR-related orphan receptor-positive LTi cells could be detected in the existing lymphoid structures. These results suggest that while LTi cells are required for the genesis of most SLOs in humans, SLO in the appendix and in gut-draining areas, as well as tertiary lymphoid organs, can be generated likely by LTi cell-independent mechanisms.
PMID:34261794 | DOI:10.1073/pnas.2108082118
Powered by WPeMatico
By Manish Butte
Front Pediatr. 2021 Jun 28;9:633692. doi: 10.3389/fped.2021.633692. eCollection 2021.
ABSTRACT
X-linked agammaglobulinemia (XLA) is an inherited immunodeficiency caused by mutations in the Bruton Tyrosine Kinase (BTK) gene. Marked neutropenia can be the initial abnormal laboratory finding in patients with XLA who are presenting with their first illness. The two cases presented herein support early consideration of evaluation for primary humoral immune deficiency in previously healthy male patients under the age of 12 months who present with neutropenia in the setting of infection shortly after passively acquired maternal antibody has sufficiently waned. Initial consideration of XLA (or other humoral immune deficiencies) in this particular population of young male neutropenic patients may afford the opportunity to avoid bone marrow biopsy in otherwise stable cases with similar presentations.
PMID:34262886 | PMC:PMC8273273 | DOI:10.3389/fped.2021.633692
Powered by WPeMatico
By Manish Butte
Pediatr Infect Dis J. 2021 Jul 13. doi: 10.1097/INF.0000000000003256. Online ahead of print.
ABSTRACT
No underlying pathology could be detected in 64% of 208 children presenting with recurrent respiratory tract infections in general pediatric practice. Asthma/preschool wheezing and adenoid hypertrophy were commonly diagnosed. None of the children had a severe primary immunodeficiency or severe pulmonary illness such as cystic fibrosis. Our findings can guide pediatricians in their diagnostic approach of children with respiratory tract infections.
PMID:34260493 | DOI:10.1097/INF.0000000000003256
Powered by WPeMatico
By Manish Butte
Allergy Asthma Proc. 2021 Jul 13. doi: 10.2500/aap.2021.42.210032. Online ahead of print.
ABSTRACT
The patient was a 33-year-old man with a history of recurrent pneumonia, autism, bipolar disorder, hypothyroidism, intermittent asthma, and nonischemic cardiomyopathy attributed to cocaine use who was admitted with hypoxemic respiratory distress with bilateral infiltrates seen on a chest radiograph. He was treated for community-acquired pneumonia but progressed to respiratory failure that required intubation and broad-spectrum antibiotic therapy. His medical history was notable for short stature, abnormal facial features, and, since childhood, at least two pneumonias per year that required antibiotics. The initial evaluation for an underlying primary immunodeficiency found that the patient had normal quantitative immunoglobulin levels, with absent CD19+ B cells. This case highlighted the evaluation of the humoral immune system for hospitalized adultpatients with recurrent infections as well as the use of genetic testing to diagnose rare immunodeficiency syndromes.
PMID:34256898 | DOI:10.2500/aap.2021.42.210032
Powered by WPeMatico
By Manish Butte
Expert Rev Clin Immunol. 2021 Jul 12. doi: 10.1080/1744666X.2021.1954908. Online ahead of print.
ABSTRACT
OBJECTIVES: Common variable immunodeficiency (CVID) patients experience clinical manifestations rather than recurrent respiratory infections including autoimmunity, enteropathy and lymphoproliferation. We evaluated correlation of lymphocyte subpopulations with such manifestations.
Methods: Twenty-six genetically unsolved CVID patients subdivided into 4 phenotypes: infection only (IO), autoimmunity (AI), chronic enteropathy (CE) and lymphoproliferative disorders (LP) were examined for B and T lymphocyte by flow cytometry and TCD4+ proliferation by Carboxyfluorescein succinimidyl ester (CFSE) test.
RESULTS: We detected reduced memory B and increased total, Effector Memory (EM), cytotoxic and activated TCD8+ in IO, AI and CE, decreased plasmablasts, total and naive TCD4+, Regulatory TCD4+ (Treg) and naive TCD8+ in IO and CE, elevated CD21low B and Terminally Differentiated Effector Memory (TEMRA) TCD8+ in IO and AI, increased helper T (Th2) and Th17 in IO, decreased Th1 in AI and defective total and naive B and Central Memory (CM) TCD4+ in CE. IO showed reduced TCD4+ proliferation response.
CONCLUSIONS: In genetically unsolved CVID patients, increased Th2 and Th17 and reduced Treg is associated with IO, increased CD21low B and TEMRA TCD8+ and reduced Th1 is contributed to AI and reduced total and naive B, CM TCD4+ and naive TCD8+ and expanded total TCD8+ is correlated with CE.
PMID:34252322 | DOI:10.1080/1744666X.2021.1954908
Powered by WPeMatico
By Manish Butte
PLoS One. 2021 Jul 12;16(7):e0254407. doi: 10.1371/journal.pone.0254407. eCollection 2021.
ABSTRACT
X-linked agammaglobulinemia (XLA, OMIM #300755) is a primary immunodeficiency disorder caused by pathogenic variations in the BTK gene, characterized by failure of development and maturation of B lymphocytes. The estimated prevalence worldwide is 1 in 190,000 male births. Recently, genome sequencing has been widely used in difficult to diagnose and familial cases. We report a large Indian family suffering from XLA with five affected individuals. We performed complete blood count, immunoglobulin assay, and lymphocyte subset analysis for all patients and analyzed Btk expression for one patient and his mother. Whole exome sequencing (WES) for four patients, and whole genome sequencing (WGS) for two patients have been performed. Carrier screening was done for 17 family members using Multiplex Ligation-dependent Probe Amplification (MLPA) and haplotype ancestry mapping using fineSTRUCTURE was performed. All patients had hypogammaglobulinemia and low CD19+ B cells. One patient who underwent Btk estimation had low expression and his mother showed a mosaic pattern. We could not identify any single nucleotide variants or small insertion/ deletions from the WES dataset that correlates with the clinical feature of the patient. Structural variant analysis through WGS data identifies a novel large deletion of 5,296 bp at loci chrX:100,624,323-100,629,619 encompassing exons 3-5 of the BTK gene. Family screening revealed seven carriers for the deletion. Two patients had a successful HSCT. Haplotype mapping revealed a South Asian ancestry. WGS led to identification of the accurate genetic mutation which could help in early diagnosis leading to improved outcomes, prevention of permanent organ damage and improved quality of life, as well as enabling genetic counselling and prenatal diagnosis in the family.
PMID:34252140 | DOI:10.1371/journal.pone.0254407
Powered by WPeMatico
By Manish Butte
Front Pediatr. 2021 Jun 25;9:652405. doi: 10.3389/fped.2021.652405. eCollection 2021.
ABSTRACT
Autosomal dominant gain-of-function mutations in the PIK3CD gene encoding the catalytic subunit p110δ of phosphoinositide 3-kinase-δ (PI3K-δ) or autosomal dominant loss-of-function mutations in the PIK3R1 gene encoding the p85α, p55α and p50α regulatory subunits cause Activated PI3-kinase-δ syndrome (APDS; referred as type 1 APDS and type 2 APDS, respectively). Consequences of these mutations are PI3K-δ hyperactivity. Clinical presentation described for both types of APDS patients is very variable, ranging from mild or asymptomatic features to profound combined immunodeficiency. Massive lymphoproliferation, bronchiectasis, increased susceptibility to bacterial and viral infections and, at a lesser extent, auto-immune manifestations and occurrence of cancer, especially B cell lymphoma, have been described for both types of APDS patients. Here, we review clinical presentation and treatment options as well as fundamental immunological and biological features associated to PI3K-δ increased signaling.
PMID:34249806 | PMC:PMC8267809 | DOI:10.3389/fped.2021.652405
Powered by WPeMatico