Manish Butte

Sarcoidosis Vasc Diffuse Lung Dis. 2021;38(3):e2021025. doi: 10.36141/svdld.v38i3.11114. Epub 2021 Sep 30.

ABSTRACT

Common variable immunodeficiency (CVID) is one of the most common primary immunodeficiency disorders characterized by hypogammaglobulinemia and inadequate antibody response to immunizations. The impaired antibody response occurs due to the failure of B cells to differentiate into plasma cells resulting in low immunoglobulins levels and increased frequency of infections. Granulomatous and Lymphocytic Interstitial Lung Disease (GLILD) is a non-infectious complication of CVID that is seen in 10-30% of cases. GLILD is a multisystem inflammatory disease involving the lungs, lymph node, liver, spleen and gastrointestinal tract that mimics sarcoidosis. This report describes a series of cases who presented with dyspnea, recurrent respiratory infections or autoimmunity and on further evaluation revealed features suggestive of GLILD. There is very limited understanding of GLILD in terms of clinical presentation, the histo-pathological logical findings, and the diagnostic criteria by itself are limited. A diagnosis of GLILD is established in cases of CVID when there is evidence of lymphoproliferation, cytopenia, autoimmune processes and a lung biopsy demonstrating lymphocytic interstitial pneumonia, follicular bronchiolitis, lymphoid hyperplasia, and/or non-necrotizing granulomas. We review the treatment strategies, including replacement of immunoglobulin and agents targeting B and T lymphocytes. Systematic characterization of GLILD cases and long term follow up studies are sorely needed to understand the natural history of GLILD.

PMID:34744421 | PMC:PMC8552568 | DOI:10.36141/svdld.v38i3.11114

Immunotherapy. 2021 Nov 8. doi: 10.2217/imt-2021-0167. Online ahead of print.

ABSTRACT

Aim: While facilitated subcutaneous immunoglobulin (fSCIG) has been evaluated in pediatric patients with primary immunodeficiency diseases in clinical trials, real-world data are lacking. Materials & methods: This multicenter, retrospective, chart review study assessed fSCIG utilization in 30 patients less than 18 years old, with primary or secondary immunodeficiency diseases. Medical records were reviewed at fSCIG initiation and at 6 months. Results: Most (90%) patients received their first fSCIG infusion at a medical facility; by 6 months, all fSCIG infusions were administered at home by the patient/caregiver, the majority infusing every 3-4 weeks into a single site. No serious adverse drug reactions occurred. Conclusion: This study supports the feasibility and tolerability of administering fSCIG at home to pediatric patients with immunodeficiencies. Clinical Trial Registration: DRKS00015436 (German Clinical Trials Register).

PMID:34743590 | DOI:10.2217/imt-2021-0167

Immunotherapy. 2021 Nov 8. doi: 10.2217/imt-2020-0313. Online ahead of print.

ABSTRACT

Aim: To describe the effects of a summertime pause (SP) in immunoglobulin replacement therapy (IgRT). Patients & methods: We conducted a prospective single-center observational study, including 44 patients undergoing intravenous IgRT between May and June 2019 in a French teaching hospital. Results: IgRT was interrupted in 23 patients from June to October. Patients who underwent an SP were older, more likely to have secondary immunodeficiency (SID) and received lower doses of immunoglobulin and more antibiotics during winter. Most patients who did not undergo an SP had severe primary immunodeficiency. The SP did not increase the risk of infection, improved the quality of life and reduced treatment costs. Conclusion: SP in IgRT is a safe practice and should be considered for patients with mild SID.

PMID:34743547 | DOI:10.2217/imt-2020-0313

Fetal Pediatr Pathol. 2021 Nov 5:1-12. doi: 10.1080/15513815.2021.2000533. Online ahead of print.

ABSTRACT

Background: Primary immunodeficiency (PID) having defects related to lymphocyte cytotoxic pathway or T-cell dysfunction are well known for developing opportunistic infections and Epstein-Barr virus (EBV)-associated diseases. CARMIL2 deficiency is a recently described combined immunodeficiency (CID) disorder characterized by defective CD28-mediated T cell co-stimulation, altered cytoskeletal dynamics, susceptibility to various infections and Epstein Barr Virus smooth muscle tumor (EBV-SMT). Case report: We report a homozygous CARMIL2 pathogenic variant presenting with recurrent infections and EBV associated smooth muscle tumor (SMT) in a child. Conclusion: The present study reports that EBV SMT may occur in a child with CARMIL2 deficiency.

PMID:34738861 | DOI:10.1080/15513815.2021.2000533

Pediatr Allergy Immunol. 2021 Nov 5. doi: 10.1111/pai.13694. Online ahead of print.

ABSTRACT

BACKGROUND: STAT1 gain-of-function (GOF) is an immune dysregulatory disorder with poorly-studied genotype-phenotype correlation, impeding prognostication and early intervention. Given previous mechanistic studies, as well as anecdotal clinical reports, we sought to systematically determine if DNA-binding domain (DBD) mutations in STAT1 result in a different phenotype than mutations in other gene domains.

METHODS: Negative prognostic features previously identified by the International STAT1 GOF Study Group (invasive infections, intracranial aneurysms and malignancy), as well as other clinical features and mortality, were compared within a cohort of 30 patients with STAT1 GOF diagnosed at our centre, consisting of 9 patients with DBD mutations and 21 patients with non-DBD mutations. We subsequently re-analyzed mortality data from a large, previously published 274-patient cohort by the International STAT1 GOF Study Group.

RESULTS: While no differences were noted with respect to malignancy or symptomatic aneurysms, invasive /opportunistic infections were substantially more common among DBD patients, as were sinopulmonary infections, bronchiectasis, enteropathy, endocrinopathies, lymphoproliferative manifestations and recurrent fevers/HLH. DBD patients also had a lower probability of survival and younger age of mortality compared with non-DBD patients. Our re-evaluation of the published data from the International STAT1 GOF Study Group revealed a similar finding of earlier mortality among patients harbouring DBD mutations.

CONCLUSION: We report that STAT1 GOF patients with DBD mutations may be regarded as a unique sub-group, impacted more by early-onset profound combined immunodeficiency and with earlier mortality. These findings may impact clinical decision making with respect to early intervention, and in particular hematopoietic stem cell consideration, in such patients.

PMID:34738677 | DOI:10.1111/pai.13694

Turk J Pediatr. 2021;63(5):801-810. doi: 10.24953/turkjped.2021.05.008.

ABSTRACT

BACKGROUND: Symptomatic COVID-19 cases in children occur mostly in those with primary immunodeficiency (PID), chronic lung diseases, and heart disease. Guidelines recommend that patients with PID continue to use their regular medication during the pandemic.

OBJECTIVES: This study aimed to evaluate anxiety related to COVID-19 in the parents of patients receiving intravenous immunoglobulin (IVIG) treatment in our hospital and to evaluate the effect of their anxiety on the continuity of treatment.

METHODS: The parents of the patients who underwent IVIG therapy in our clinic during the pandemic (between May 15, 2020 and July 1, 2020) were included in our study.

RESULTS: Twenty-seven patients with PID whose IVIG therapy was initiated before the pandemic and 29 non- PID control subjects were included in the study. All patients received IVIG treatment in our clinic continued treatment during the pandemic at the same dose intervals. Parents in the IVIG group had significantly higher state (p=0.003) and trait (p=0.003) anxiety scores compared to control parents. IVIG group showed statistically significant higher scores in Beck depression inventory, than the control group (p=0.002).

CONCLUSIONS: The parents of PID patients who needed to come to the hospital for IVIG therapy had higher anxiety levels than the parents of similar aged children who presented to our clinic for different complaints between the same dates. Despite their concerns, the parents of all patients under IVIG therapy maintained treatment continuity at the recommended treatment intervals. None of our immunodeficient patients who presented for treatment during the pandemic contracted COVID-19 infection during our study.

PMID:34738362 | DOI:10.24953/turkjped.2021.05.008

Eur J Cancer. 2021 Oct 9;159:78-86. doi: 10.1016/j.ejca.2021.09.027. Online ahead of print.

ABSTRACT

PURPOSE: There are limited data on SARS-CoV-2 (COVID-19) infection in children with cancer or after haematopoietic stem cell transplant (HSCT). We describe the severity and outcomes of SARS-COV-2 in these patients and identify factors associated with severe disease.

METHODS: This was a multinational, observational study of children (aged <19 years) with cancer or HSCT and SARS-CoV-2 confirmed by polymerase chain reaction. COVID-19 was classified as asymptomatic, mild, moderate, severe or critical (≥1 organ support). Exact polytomous regression was used to determine the relationship between clinical variables and disease severity.

RESULTS: One hundred and thirty-one patients with COVID-19 across 10 countries were identified (median age 8 years). Seventy-eight (60%) had leukaemia/lymphoma, 48 (37%) had solid tumour and five had primary immunodeficiency and HSCT. Fever (71%), cough (47%) and coryza (29%) were the most frequent symptoms. The median duration of detectable virus was 16 days (range, 1-79 days). Forty-nine patients (37%) were hospitalised for COVID-19 symptoms, and 15 (11%) required intensive care unit-level care. Chemotherapy was delayed/modified in 35% of patients. COVID-19 was asymptomatic in 32% of patients, mild in 47%, moderate in 8%, severe in 4% and critical in 9%. In 124 patients (95%), a full recovery was documented, and four (3%) died due to COVID-19. Any comorbidity (odds ratio, 2.94; 95% confidence interval [CI], 1.81-5.21), any coinfection (1.74; 95% CI 1.03-3.03) and severe baseline neutropenia (1.82; 95% CI 1.13-3.09) were independently and significantly associated with increasing disease severity.

CONCLUSION: Although most children with cancer had asymptomatic/mild disease, 13% had severe COVID-19 and 3% died. Comorbidity, coinfection and neutropenia may increase the risk of severe disease. Our data may help management decisions in this vulnerable population.

PMID:34736044 | DOI:10.1016/j.ejca.2021.09.027

Afr J Thorac Crit Care Med. 2021 Oct 4;27(3). doi: 10.7196/AJTCCM.2021.v27i3.228. eCollection 2021.

ABSTRACT

Primary immune deficiency disorders (PIDDs) are common and underdiagnosed. Predominant antibody deficiencies (PADs) are the most common type of immune deficiency and comprise 55% of the immune deficiencies diagnosed.^[1] Although immunoglobulin A (IgA) deficiency remains the most common type of PID, common variable immunodeficiency disorders remain the most common symptomatic PID for which medical therapy is sought.

PMID:34734174 | PMC:PMC8547339 | DOI:10.7196/AJTCCM.2021.v27i3.228

J Clin Immunol. 2021 Nov 3. doi: 10.1007/s10875-021-01165-6. Online ahead of print.

ABSTRACT

PURPOSE: Chronic granulomatous disorder (CGD) is a primary immunodeficiency which is frequently complicated by inflammatory colitis and is associated with systemic inflammation. Herein, we aimed to investigate the role of the microbiome in the pathogenesis of colitis and systemic inflammation.

METHODS: We performed 16S rDNA sequencing on mucosal biopsy samples from each segment of 10 CGD patients’ colons and conducted compositional and functional pathway prediction analyses.

RESULTS: The microbiota in samples from colitis patients demonstrated reduced taxonomic alpha-diversity compared to unaffected patients, even in apparently normal bowel segments. Functional pathway richness was similar between the colitic and non-colitic mucosa, although metabolic pathways involved in butyrate biosynthesis or utilization were enriched in patients with colitis and correlated positively with fecal calprotectin levels. One patient with very severe colitis was dominated by Enterococcus spp., while among other patients Bacteroides spp. abundance correlated with colitis severity measured by fecal calprotectin and an endoscopic severity score. In contrast, Blautia abundance is associated with low severity scores and mucosal health. Several taxa and functional pathways correlated with concentrations of inflammatory cytokines in blood but not with colitis severity. Notably, dividing patients into “high” and “low” systemic inflammation groups demonstrated clearer separation than on the basis of colitis status in beta-diversity analyses.

CONCLUSION: The microbiome is abnormal in CGD-associated colitis and altered functional characteristics probably contribute to pathogenesis. Furthermore, the relationship between the mucosal microbiome and systemic inflammation, independent of colitis status, implies that the microbiome in CGD can influence the inflammatory phenotype of the condition.

PMID:34731398 | DOI:10.1007/s10875-021-01165-6

Allergy Asthma Clin Immunol. 2021 Nov 2;17(1):115. doi: 10.1186/s13223-021-00617-3.

ABSTRACT

Severe combined immunodeficiency (SCID) is a rare genetic condition characterized by significant T cell lymphopenia and impaired T cell function. Many jurisdictions use the quantitation of T cell receptor excision circles (TRECs) to screen for SCID in newborns, but false positives may be seen in several conditions. We report 3 newborns with neonatal abstinence syndrome who presented with decreased TREC copy number.

PMID:34727967 | DOI:10.1186/s13223-021-00617-3