Pulmonary Manifestations of Predominantly Antibody Deficiencies
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SUBMITTER: Mahdaviani S
PROVIDER: S-EPMC7123456 | biostudies-literature | 2019 Jan
REPOSITORIES: biostudies-literature
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Project description:BackgroundPredominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy.ObjectivesTo characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia.MethodsWe identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features.Results179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7?years (range: 16-87?years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1?year. The median age of reported symptom onset was 20?years for those with a diagnosis of CVID, with a median age at diagnosis of 35?years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort.ConclusionOur data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.
| S-EPMC5960671 | biostudies-literature
Project description:Predominantly antibody deficiencies (PADs) are inborn disorders characterized by immune dysregulation and increased susceptibility to infections. Response to vaccination, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be impaired in these patients, and studies on responsiveness correlates, including cytokine signatures to antigen stimulation, are sparse. In this study, we aimed to describe the spike-specific cytokine response following whole-blood stimulation with SARS-CoV-2 spike peptides in patients with PAD (n = 16 with common variable immunodeficiency and n = 15 with selective IgA deficiency) and its relationship with the occurrence of coronavirus disease 2019 (COVID-19) during up to 10-month follow-up period. Spike-induced antibody and cytokine production was measured using ELISA (anti-spike IgG, IFN-γ) and xMAP technology (interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-15, IL-17A, IL-21, TNF-α, TGF-β1). No difference was found in the production of cytokines between patients with PAD and controls. Anti-spike IgG and cytokine levels did not predict contraction of COVID-19. The only cytokine that distinguished between vaccinated and naturally infected unvaccinated PAD patients was IFN-γ (median 0.64 (IQR = 1.08) in vaccinated vs. 0.10 (IQR = 0.28) in unvaccinated). This study describes the spike-specific cytokine response to SARS-CoV-2 antigens, which is not predictive of contracting COVID-19 during the follow-up.
| S-EPMC10222647 | biostudies-literature
Project description:ObjectiveThis minireview gathers the scientific foundations of the literature on genetic errors in the development of the humoral immune system to help pediatricians suspect these defects.SourcesA systemic search using the PubMed MEDLINE database was performed for all Predominantly Antibody Deficiencies (PADs) described in the 2020 IUIS Expert Committee for PID classification system, combined with terms for hypogammaglobulinemia. Search terms for PADs were based on the listed names and affected genes as classified by the IUIS 2020. Abstracts of the results were reviewed to find relevant case series, review articles of PADs associated with infection, opportunistic infection, autoimmunity, cytopenias, malignancies, inflammatory diseases, neurological and respiratory diseases. References from relevant articles were further reviewed for additional references. Relevant findings were grouped in accordance with the IUIS 2020 classification system. Clinical and genetic features, if known, were described.Data synthesisPADs refer to impaired antibody production due to molecular defects intrinsic to B cells or a failure of interaction between B and T cells. The patients develop recurrent or chronic infection or respond to the antigens with dysregulation of the immune function, causing severe allergy, autoimmunity, inflammation, lymphoproliferation and malignancy. The diagnosis is a combined exercise of clinical and laboratory investigation similar to that performed by Bruton (1952). In the context of SARS-CoV-2 infection, the experience of XLA and CVID patients has been surprising. Variants in 39 genes were reported as causing PADs, but the clinical heterogeneity within each variant is not clear.ConclusionBruton (1952) used clinical expertise and protein electrophoresis to identify XLA. The IUIS (2020) committee used immunoglobulins and B lymphocyte to characterize PADs. Pediatricians should suspect it to detect it and prevent morbidities that can have an astonishing and irreversible impact on the child's life.
| S-EPMC9432301 | biostudies-literature
Project description:Secondary antibody deficiencies (SAD) may require immunoglobulin replacement therapy (IgRT). While the intravenous route (IVIG) is broadly considered effective in SAD, the use of subcutaneous immunoglobulins (SCIG) is mainly adopted from the experience in primary antibody deficiencies (PAD), where SCIG have been shown to perform as effective as IVIG. However, evidence-based data on SCIG administration in SAD patients are still insufficient. Herein we retrospectively evaluated the efficacy and safety profile of SCIG treatment in 131 SAD patients as compared to a group of 102 PAD patients. We found SCIG being equally effective in reducing annual infectious rate both in SAD and PAD patients. However, SAD patients required lower SCIG dosage and lower IgG through level to achieve similar biological effect in terms of infection burden, at the steady state. SAD patients also showed better correlation between SCIG dose and serum IgG achieved value. Furthermore, within SAD, SCIG were found to work irrespective of the underlying disease. Especially in Non-Hodgkin Lymphoma patients, whose indication to IgRT is still not included in all guidelines and for whom evidence-based data are still lacking, SCIG were as effective as in Chronic Lymphocytic Leukemia or Multiple Myeloma patients, and SCIG discontinuation, without evidence of B cell recovery, led to IgG decline and relapsed infections. Finally, treatment tolerance in SAD patients was comparable to the PAD cohort. Globally, our data suggest that SCIG, as already appreciated in PAD, represent a valuable option in SAD patients, independent on the disease leading to antibody deficiency.
| S-EPMC7932095 | biostudies-literature
Project description:In 9-20% of cases, Sjögren's syndrome is associated with various respiratory symptoms. The most typical manifestations are chronic interstitial lung disease (ILD) and tracheobronchial disease. The most common manifestation of ILD is nonspecific interstitial pneumonia in its fibrosing variant. Other types of ILD, such as organising pneumonia, usual interstitial pneumonia and lymphocytic interstitial pneumonitis, are rare. Their radiological presentation is less distinctive, and definitive diagnosis may require the use of transbronchial or surgical lung biopsy. Corticosteroid therapy is the mainstay of ILD treatment in Sjögren's syndrome, but the use of other immunosuppressive drugs needs to be determined. ILD is a significant cause of death in Sjögren's syndrome. Tracheobronchial disease is common in Sjögren's syndrome, characterised by diffuse lymphocytic infiltration of the airway. It is sometimes responsible for a crippling chronic cough. It can also present in the form of bronchial hyperresponsiveness, bronchiectasis, bronchiolitis or recurrent respiratory infections. The management of these manifestations may require treatment for dryness and/or inflammation of the airways. Airway disease has little effect on respiratory function and is rarely the cause of death in Sjögren's syndrome patients. Rare respiratory complications such as amyloidosis, lymphoma or pulmonary hypertension should not be disregarded in Sjögren's syndrome patients.
| S-EPMC9487244 | biostudies-literature
Project description:Bronchiectasis, the presence of bronchial wall thickening with airway dilatation, is a particularly challenging complication of primary antibody deficiencies. While susceptibility to infections may be the primary factor leading to the development of bronchiectasis in these patients, the condition may develop in the absence of known infections. Once bronchiectasis is present, the lungs are subject to a progressive cycle involving both infectious and non-infectious factors. If bronchiectasis is not identified or not managed appropriately, the cycle proceeds unchecked and yields advanced and permanent lung damage. Severe symptoms may limit exercise tolerance, require frequent hospitalizations, profoundly impair quality of life (QOL), and lead to early death. This review article focuses on the appropriate identification and management of bronchiectasis in patients with primary antibody deficiencies. The underlying immune deficiency and the bronchiectasis need to be treated from combined immunology and pulmonary perspectives, reflected in this review by experts from both fields. An aggressive multidisciplinary approach may reduce exacerbations and slow the progression of permanent lung damage.
| S-EPMC7138103 | biostudies-literature
Project description:The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been recently identified as the culprit of the highly infectious, outbreak named coronavirus disease 2019 (COVID-19) in China. Now declared a public health emergency, this pandemic is present in more than 200 countries with over 14 million cases and 600,000 deaths as of July 18, 2020. Primarily transmitted through the respiratory tract, the most common clinical presentations of symptomatic individuals infected with SARS-CoV-2 include fever, dyspnea, cough, fatigue, and sore throat. In advanced cases, patients may rapidly develop respiratory failure with acute respiratory distress syndrome, and even progress to death. While it is known that COVID-19 manifests similarly to the 2003 Severe Acute Respiratory Syndrome (SARS) and the 2012 Middle East Respiratory Syndrome (MERS), primarily affecting the pulmonary system, the impact of the disease extends far beyond the respiratory system and affects other organs of the body. The literature regarding the extrapulmonary manifestations (cardiovascular, renal, hepatic, gastrointestinal, ocular, dermatologic, and neurological) of COVID-19 is scant. Herein, we provide a comprehensive review of the organ-specific clinical manifestations of COVID-19, to increase awareness about the various organs affected by SARS-CoV-2 and to provide a brief insight into the similarities and differences in the clinical manifestations of COVID-19 and the earlier SARS and MERS.
| S-EPMC7438449 | biostudies-literature
Project description:Tuberous sclerosis complex has manifestations in many organ systems, including brain, heart, kidney, skin, and lung. The primary manifestations in the lung are lymphangioleiomyomatosis (LAM) and multifocal micronodular pneumocyte hyperplasia (MMPH). LAM affects almost exclusively women, and causes cystic lung destruction, pneumothorax, and chylous pleural effusions. LAM can lead to dyspnea, oxygen dependence, and respiratory failure, with more rapid disease progression during the premenopausal years. In contrast, MMPH affects men and women equally, causing small nodular pulmonary deposits of type II pneumocytes that rarely progress to symptomatic disease. Here, we review the clinical features and pathogenesis of LAM and MMPH.
| S-EPMC6209521 | biostudies-literature
Project description:BackgroundIn primary antibody deficiencies (PADs), pulmonary complications are the main cause of morbidity, despite immunoglobulin substitutive therapy, antibiotic treatment of exacerbations, and respiratory physiotherapy. Current Italian recommendations for surveillance of PADs respiratory complications include an annual assessment of spirometry and execution of chest high-resolution computed tomography (HRCT) every 4 years.ObjectiveThis study aimed to evaluate the effectiveness of the lung clearance index (LCI) as an early marker of lung damage in patients with PADs. LCI is measured by multiple breath washout (MBW), a non-invasive and highly specific test widely used in patients with cystic fibrosis (CF).MethodsPediatric patients with PADs (n = 17, 10 male, 7 female, and age range 5-15 years) underwent baseline assessment of lung involvement with chest HRCT, spirometry, and multiple breath nitrogen washout. Among them, 13 patients were followed up to repeat HRCT after 4 years, while performing pulmonary function tests annually. Their baseline and follow-up LCI and forced expiratory volume at 1 s (FEV1) values were compared, taking HRCT as the gold standard, using logistic regression analysis.ResultsLung clearance index [odds ratio (OR) 2.3 (confidence interval (CI) 0.1-52) at baseline, OR 3.9 (CI 0.2-191) at follow-up] has a stronger discriminating power between altered and normal HRCT rather than FEV1 [OR 0.6 (CI 0.2-2) at baseline, OR 1.6 (CI 0.1-13.6) at follow-up].ConclusionWithin the context of a limited sample size, LCI seems to be more predictive of HRCT alterations than FEV1 and more sensitive than HRCT in detecting non-uniform ventilation in the absence of bronchiectasis. A study of a larger cohort of pediatric patients followed longitudinally in adulthood is needed to challenge these findings.
| S-EPMC9152221 | biostudies-literature
Project description:PurposeTo investigate pulmonary vascular abnormalities at CT pulmonary angiography (CT-PE) in patients with coronavirus disease 2019 (COVID-19) pneumonia.Materials and methodsIn this retrospective study, 48 patients with reverse-transcription polymerase chain reaction-confirmed COVID-19 infection who had undergone CT-PE between March 23 and April 6, 2020, in a large urban health care system were included. Patient demographics and clinical data were collected through the electronic medical record system. Twenty-five patients underwent dual-energy CT (DECT) as part of the standard CT-PE protocol at a subset of the hospitals. Two thoracic radiologists independently assessed all studies. Disagreement in assessment was resolved by consensus discussion with a third thoracic radiologist.ResultsOf the 48 patients, 45 patients required admission, with 18 admitted to the intensive care unit, and 13 requiring intubation. Seven patients (15%) were found to have pulmonary emboli. Dilated vessels were seen in 41 cases (85%), with 38 (78%) and 27 (55%) cases demonstrating vessel enlargement within and outside of lung opacities, respectively. Dilated distal vessels extending to the pleura and fissures were seen in 40 cases (82%) and 30 cases (61%), respectively. At DECT, mosaic perfusion pattern was observed in 24 cases (96%), regional hyperemia overlapping with areas of pulmonary opacities or immediately surrounding the opacities were seen in 13 cases (52%), opacities associated with corresponding oligemia were seen in 24 cases (96%), and hyperemic halo was seen in 9 cases (36%).ConclusionPulmonary vascular abnormalities such as vessel enlargement and regional mosaic perfusion patterns are common in COVID-19 pneumonia. Perfusion abnormalities are also frequently observed at DECT in COVID-19 pneumonia and may suggest an underlying vascular process.Supplemental material is available for this article.© RSNA, 2020.
| S-EPMC7307217 | biostudies-literature