Manish Butte

Allergol Immunopathol (Madr). 2022 Jan 1;50(1):80-84. doi: 10.15586/aei.v50i1.388. eCollection 2022.

ABSTRACT

BACKGROUND: Inborn errors of immunity (IEIs) are a group of congenital diseases caused by genetic defects in the development and function of the immune system. The involvement of the respiratory tract is one of the most common presentations in IEIs.

METHODS: Overall, 117 patients with diagnosed IEIs were followed-up within 8 years at the National Research Institute of Tuberculosis and Lung Diseases (NRITLD). Demographic, clinical, and laboratory data were collected in a questionnaire. Pulmonary function test (PFT), chest X-ray (CXR), and high-resolution computed tomography (HRCT) scans were obtained where applicable.

RESULTS: Our study population consisted of 48 (41%) patients with predominantly antibody deficiencies (PADs), 39 (32%) patients with congenital defects of phagocytes, 14 (11.9%) patients with combined immunodeficiency (CID), and 16 (14%) patients with Mendelian susceptibility to mycobacterial diseases (MSMD). . Recurrent pneumonia was the most common manifestation, while productive cough appeared to be the most common symptom in almost all diseases. PFT showed an obstructive pattern in patients with PAD, a restrictive pattern in patients with CID, and a mixed pattern in patients with CGD. HRCT findings were consistent with bronchiectasis in most PAD patients, whereas consolidation and mediastinal lesions were more common in the other groups.

CONCLUSIONS: Pulmonary manifestations vary among different groups of IEIs. The screening for lung complications should be performed regularly to reveal respiratory pathologies in early stages and follow-up on already existing abnormalities.

PMID:34935317 | DOI:10.15586/aei.v50i1.388

Einstein (Sao Paulo). 2021 Dec 17;19:eAO6289. doi: 10.31744/einstein_journal/2021AO6289. eCollection 2021.

ABSTRACT

OBJECTIVE: To investigate the level of awareness of primary immunodeficiency diseases among physicians working at Instituto Nacional de Salud del Niño.

METHODS: Cross-sectional study including pediatric residents and pediatricians working at the Instituto Nacional de Salud del Niño during the study period (2017-2019). Physicians working at the immunology unit and surgery departments were excluded. Three aspects of awareness of primary immunodeficiency diseases were investigated: education, general knowledge, and diagnostic suspicion and actions taken in the face of suspicion.

RESULTS: This sample comprised 83 physicians with a median age of 33 years. Most physicians were women (71.1%) and half were pediatric residents. During their undergraduate studies, 43.1% had taken primary immunodeficiency disease courses, and 39.2% had attended conferences on this topic. During their residency training, 25.9% had taken primary immunodeficiency disease courses, and 60.3% had participated in conferences on this topic. Among pediatricians, 50% had taken primary immunodeficiency disease courses, and 53.1% had attended conferences on this topic. Only 39.8% of physicians reported being familiar with the list of 10 warning signs developed by the Jeffrey Modell Foundation. More than half of physicians considered the lack of access to laboratory tests the major challenge in making diagnosis of primary immunodeficiency diseases.

CONCLUSION: This study revealed limited awareness of primary immunodeficiency diseases among physicians working at Instituto Nacional de Salud del Niño. Although most physicians suspected primary immunodeficiency diseases in patients with a history of recurrent infections and frequent use of antibiotics, not all of them were familiar with the list of 10 warning signs proposed by the Jeffrey Modell Foundation, nor were they able to describe ancillary tests requested in suspected cases.

PMID:34932757 | DOI:10.31744/einstein_journal/2021AO6289

Rev Col Bras Cir. 2021 Dec 15;48:e20213133. doi: 10.1590/0100-6991e-20213133. eCollection 2021.

ABSTRACT

INTRODUCTION: although it is a rare disease, common variable immunodeficiency (CVID) stands out as the most frequent primary symptomatic immunodeficiency. Carriers are prone to a variety of recurrent bacterial infections, in addition to the risk of developing autoimmune diseases and neoplasms including gastric cancer (GC). Despite the recognized risk, there are no specific standardized protocols for the management of GC in these patients, so the reported oncological results are varied. Thus, this study aims to describe the clinicopathological characteristics and prognosis of patients with CVID undergoing surgical treatment of GC.

METHODS: all patients with GC undergoing surgical treatment between 2009 and 2020 were retrospectively evaluated. Later, patients diagnosed with CVID were identified and this group was compared with the remaining patients without any immunodeficiency.

RESULTS: among the 1101 patients with GC evaluated in the period, 10 had some type of immunodeficiency, and 5 were diagnosed with CVID. Patients with CVID had younger age, lower BMI, and smaller lesions compared to those without CVID. Four patients underwent curative gastrectomy and one patient underwent jejunostomy. Two patients died (1 palliative and 1 curative) and one patient had disease recurrence. There was no statistically significant difference regarding the incidence of postoperative complications and survival between the evaluated groups.

CONCLUSION: the CVID incidence in patients with GC undergoing surgical treatment was 0.5%, occurring at a less advanced age, but with no difference regarding surgical and oncological results.

PMID:34932733 | DOI:10.1590/0100-6991e-20213133

Immunotherapy. 2021 Dec 21. doi: 10.2217/imt-2021-0256. Online ahead of print.

ABSTRACT

Aim: This post hoc analysis evaluated the efficacy and overall tolerability of immunoglobulin (Ig) treatment modalities (intravenous Ig [iv.Ig], subcutaneous Ig [sc.Ig] and facilitated sc.Ig [fsc.Ig]). Materials & methods: A total of 30 participants with primary immunodeficiency diseases aged ≥2 years sequentially received iv.Ig, sc.Ig and fsc.Ig during consecutive clinical studies. Results: For iv.Ig, sc.Ig and fsc.Ig, rates of validated acute serious bacterial infections/participant-year (0, 0.09 and 0.04, respectively) and all infections/participant year (4.17, 3.68 and 2.42, respectively) were similarly low; rates of systemic and local causally related adverse events/participant-year were 5.60, 1.93 and 0.88, respectively and 0.13, 0.92 and 1.57, respectively. Conclusion: fsc.Ig provided similar efficacy to iv.Ig and sc.Ig. Clinical Trial registration: NCT00546871, NCT00814320, NCT01175213 (ClinicalTrials.gov).

PMID:34931880 | DOI:10.2217/imt-2021-0256

Clin Immunol. 2021 Dec 15:108910. doi: 10.1016/j.clim.2021.108910. Online ahead of print.

ABSTRACT

Genetic variants in PIK3CD, PIK3R1 and NFKB1 cause the primary immune deficiencies, activated PI3Kδ syndrome (APDS) 1, APDS2 and NFκB1 haploinsufficiency, respectively. We have identified a family with known or potentially pathogenic variants NFKB1, TNFRSF13B and PIK3R1. The study’s aim was to describe their associated immune and cellular phenotypes and compare with individuals with monogenic disease. NFκB1 pathway function was measured by immunoblotting and PI3Kδ pathway activity by phospho-flow cytometry. p105/p50 expression was absent in two individuals but elevated pS6 only in the index case. Transfection of primary T cells demonstrated increased basal pS6 signalling due to mutant PIK3R1, but not mutant NFKB1 or their wildtype forms. We report on the presence of pathogenic variant NFKB1, with likely modifying variants in TNFRSF13B and PIK3R1 in a family. We describe immune features of both NFκB1 haploinsufficiency and APDS2, and the inhibition of excessive PI3K signalling by rapamycin in vitro.

PMID:34922003 | DOI:10.1016/j.clim.2021.108910

Iran J Allergy Asthma Immunol. 2021 Dec 8;20(6):778-783. doi: 10.18502/ijaai.v20i6.8030.

ABSTRACT

Although the majority of monogenic defects underlying primary immunodeficiency are microlesions, large lesions like large deletions are rare and constitute less than 10% of these patients. The immunoglobulin heavy chain (IGH) locus is one of the common regions for such genetic alterations. This study describes a rare case of autosomal recessive agammaglobulinemia with a homozygous large deletion in chromosome 14q32.33 (106067756-106237742) immunoglobulin heavy chain clusters with an unusual and severe skin infection and disseminated intravascular coagulopathy.

PMID:34920661 | DOI:10.18502/ijaai.v20i6.8030

Iran J Allergy Asthma Immunol. 2021 Dec 8;20(6):700-710. doi: 10.18502/ijaai.v20i6.8021.

ABSTRACT

Common variable immunodeficiency (CVID) is the most prevalent form of symptomatic primary humoral immunodeficiencies characterized by failure in the final differentiation of B lymphocytes. The majority of CVID cases have no identified genetic defect, and epigenetic alteration could be involved in the pathogenesis of CVID. Hence, we aimed to evaluate the expression of hsa-miR-125b-5p -and, B lymphocyte-induced maturation protein-1(BLIMP-1) and interferon regulatory protein-4 (IRF-4) in a group of CVID patients with no definitive genetic diagnosis in comparison with healthy individuals. Ten CVID patients (all known genes excluded) and 10 age and sex-matched healthy controls participated in the study. B lymphocytes were isolated and expression of miR-125b-5p, IRF4, and BLIMP1 were evaluated by real-time polymerase chain reaction (RT-PCR). Moreover, B cell subsets were analyzed by flow cytometry. The results showed that the relative expression of miR-125b-5p in CVID patients was increased while it was decreased for the BLIMP1 and IRF4 transcription factors compared with the healthy controls. Although a reduction was observed in switched and non-switched memory B cells among all high-miR patients, these subsets were decreased in patients with normal miR expression (71.0% and 85.0%, respectively). Our results suggest that overexpression of miR-125b-5p affects the terminal differentiation of B cells in a selected group of CVID patients by downregulating the BLIMP-1 gene and more intensively for the IRF-4 gene expressions.

PMID:34920653 | DOI:10.18502/ijaai.v20i6.8021

Iran J Allergy Asthma Immunol. 2021 Dec 8;20(6):693-699. doi: 10.18502/ijaai.v20i6.8020.

ABSTRACT

Respiratory diseases are considered as significant causes of morbidity and mortality in primary immunodeficiencies. This study aimed to reveal the radiologic patterns of thoracic involvement in these disorders. A total of 58 patients, including 38 cases with combined cellular-humoral and 20 cases with humoral immunodeficiencies, were enrolled in this study. The “combined” group consisted of 12 cases with severe combined immunodeficiency (SCID) and 26 cases with combined immunodeficiency. The “humoral” group included seven patients with Hyper IgM syndrome (HIGMs), seven cases with common variable immunodeficiency (CVID), three patients with X-linked agammaglobulinemia, and three patients with other types of humoral primary immunodeficiencies (PIDs). The mean age of patients at the time of evaluation was 3.3±3.8 and 5.3±3.9 years in combined and humoral groups, respectively. The findings of chest X-rays and CT scans were interpreted and compared. There was a significant difference for alveolar opacification between combined and humoral immunodeficiencies (58% vs. 30%). The bronchopneumonia-like pattern was detected as a significant finding in patients with SCID (42%) and HIGMs (43%). Atrophy of the thymus was detected significantly often in cases of SCID (67%). Two patients with CVID and lipopolysaccharide-responsive and beige-like anchor protein deficiency showed parenchymal changes of granulomatous lymphocytic interstitial lung disease. No significant difference was detected for bronchiectasis, bronchitis/bronchiolitis patterns, pleural effusion, and thoracic lymphadenopathy. Distinct subtypes of primary immunodeficiency may provoke differing and comparable radiological patterns of thoracic involvement; which can clue the clinician and radiologist to the diagnosis of the disease.

PMID:34920652 | DOI:10.18502/ijaai.v20i6.8020

J Allergy Clin Immunol. 2021 Dec 14:S0091-6749(21)02597-5. doi: 10.1016/j.jaci.2021.10.037. Online ahead of print.

ABSTRACT

BACKGROUND: X-linked inhibitor of apoptosis (XIAP) deficiency is a rare, primary immunodeficiency disease caused by XIAP gene mutations. A broad range of phenotype, severity, and age of onset present challenges for patient management.

OBJECTIVE: To characterize the phenotype, treatment, and survival outcomes of XIAP deficiency and assess parameters influencing prognosis.

METHODS: Data published from 2006-2020 were retrospectively analyzed.

RESULTS: 167 patients from 117 families with XIAP deficiency were reported with 90 different mutations. A wide spectrum of clinical features were seen, of which hemophagocytic lymphohistiocytosis (HLH) and inflammatory bowel disease (IBD) were the most common. Patients frequently developed multiple features with no clear genotype-phenotype correlation. 117 patients were managed conservatively and 50 underwent hematopoietic stem cell transplantation (HSCT), with respective overall survival probabilities of 90% and 53% at age 16 years. The predominant indication for HSCT was early-onset HLH. Active HLH and myeloablative conditioning regimens increased HSCT-related mortality, although HSCT outcome was much better after 2015 than before. For conservatively managed patients reaching adulthood, survival probabilities were 86% at age 30 years and 37% by age 52 years, with worse outcomes for patients developing the disease before the age of 5 years or with new disease features in adulthood. 9 asymptomatic mutation carriers were identified with a median age of 13.5 years.

CONCLUSIONS: Our study demonstrates the variable nature of XIAP deficiency which evolves over life for individual patients. Better therapeutic strategies and prospective studies are required to reduce morbidity and mortality and improve decision-making and long-term outcomes for patients with XIAP deficiency.

PMID:34920033 | DOI:10.1016/j.jaci.2021.10.037

Pediatr Nephrol. 2021 Dec 17. doi: 10.1007/s00467-021-05378-0. Online ahead of print.

NO ABSTRACT

PMID:34919150 | DOI:10.1007/s00467-021-05378-0