Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia

Cho, Kazutoshi; Yamada, Masafumi; Agematsu, Kazunaga; Kanegane, Hirokazu; Miyake, Noriko; Ueki, Minoru; Akimoto, Takuma; Kobayashi, N.; Ikemoto, Satoru; Tanino, Mishie; Fujita, Atsushi; Hayasaka, Ichirô; Miyamoto, Satoshi; Tanaka-Kubota, Mari; Nakata, Koh; Shiina, Masaaki; Ogata, Kazuhiro; Minakami, Hisanori; Matsumoto, Naomichi; Ariga, Tadashi

doi:10.1016/j.ajhg.2018.01.019

Cited by 30 publications

(22 citation statements)

References 38 publications

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“…Another current interest includes OAS1 deficiency. Patients with OAS1 deficiency show hypogammaglobulinemia and pulmonary alveolar proteinosis (PAP) from infancy with defects in B cells and monocytes [ 38 ]. The disorder has already been reported, and the identified mutations include A76V, C109Y, and L198V.…”

Section: Main Textmentioning

confidence: 99%

Inborn errors of immunity—recent advances in research on the pathogenesis

et al. 2021

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Primary immunodeficiency (PID) is a genetic disorder with a defect of one of the important components of our immune system. Classical PID has been recognized as a disorder with loss of function of the immune system. Recent studies have unveiled disorders with immune dysfunction with autoimmunity, autoinflammation, allergy, or predisposition to malignancy. Some of them were caused by an augmented immune function or a defect in immune regulation. With this background, the term inborn errors of immunity (IEI) is now used to refer to PID in the International Union of Immunological Societies (IUIS) classification. More than 400 responsible genes have been identified in patients with IEI so far, and importantly, many of them identified lately were caused by a heterologous mutation. Moreover, the onset is not necessarily in childhood, and we started seeing more and more IEI patients diagnosed in adulthood in the clinical settings. Recent advances in genetic analysis, including whole-exome analysis, whole-genome analysis, and RNA-seq have contributed to the identification of the disease-causing gene mutation. We also started to find heterogeneity of phenotype even in the patients with the same mutation in the same family, leading us to wonder if modifier gene or epigenetic modification is involved in the pathogenesis. In contrast, we accumulated many cases suggesting genetic heterogeneity is associated with phenotypic homogeneity. It has thus become difficult to deduce a responsible gene only from the phenotype in a certain type of IEI. Current curative therapy for IEI includes hematopoietic cell transplantation and gene therapy. Other curative therapeutic modalities have been long waited and are to be introduced in the future. These include a small molecule that inhibits the gain-of-function of the molecule- and genome-editing technology. Research on IEI will surely lead to a better understanding of other immune-related disorders including rheumatic diseases and atopic disorders.

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Section: Main Textmentioning

confidence: 99%

Inborn errors of immunity—recent advances in research on the pathogenesis

et al. 2021

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“…While explanations for hematological disorders might seem rather obvious, the associations with nonhematological causes of secondary PAP are more complicated. Here, a variety of different diseases have been described in association with secondary PAP, like the systemic vasculitis Behçet syndrome [ 47 ], systemic lupus erythematosus [ 48 ], Wegener’s granulomatosis [ 37 ], lysinuric protein intolerance [ 49 ], OAS1 [ 50 ] and MARS mutations [ 51 ]. A special case is also inhalation of chemicals or dust as a driver of PAP.…”

Section: The Implication Of Ams In Lung Diseasesmentioning

confidence: 99%

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Hetzel

Ackermann

Lachmann

2021

IJMS

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Macrophages act as immune scavengers and are important cell types in the homeostasis of various tissues. Given the multiple roles of macrophages, these cells can also be found as tissue resident macrophages tightly integrated into a variety of tissues in which they fulfill crucial and organ-specific functions. The lung harbors at least two macrophage populations: interstitial and alveolar macrophages, which occupy different niches and functions. In this review, we provide the latest insights into the multiple roles of alveolar macrophages while unraveling the distinct factors which can influence the ontogeny and function of these cells. Furthermore, we will highlight pulmonary diseases, which are associated with dysfunctional macrophages, concentrating on congenital diseases as well as pulmonary infections and impairment of immunological pathways. Moreover, we will provide an overview about different treatment approaches targeting macrophage dysfunction. Improved knowledge of the role of macrophages in the onset of pulmonary diseases may provide the basis for new pharmacological and/or cell-based immunotherapies and will extend our understanding to other macrophage-related disorders.

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“…This underscores the need to make PAP of unknown cause a trigger for immunological review. Congenital immunodeficiencies include agammaglobulinaemia [ 52 ], severe combined immunodeficiency secondary to adenosine deaminase deficiency [ 53 ], secondary haemophagocytic lymphohistiocytosis [ 54 ], infantile hypogammaglobulinaemia with heterozygous OAS1 mutations [ 55 ], hyper-IgM syndrome [ 56 , 57 ], and sporadic and autosomal dominant monocytopenia [ 58 ]. Bone marrow or stem cell transplant may be curative for some immunodeficiencies and specialist advice should always be sought [ 41 ].…”

Section: Aetiologymentioning

confidence: 99%

Pulmonary alveolar proteinosis in children

Bush

Pabary

2020

Breathe

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Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. There is outlining of the secondary pulmonary lobules on the background of ground-glass shadowing and pathologically, filling of the alveolar spaces with normal or abnormal surfactant. PAP is rare and the common causes in children are very different from those seen in adults; autoimmune PAP is rare and macrophage blockade not described in children. There are many genetic causes of PAP, the best known of which are mutations in the genes encoding surfactant protein (SP)-B, SP-C, thyroid transcription factor 1, ATP-binding cassette protein 3, and the granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor α- and β- chains. PAP may also be a manifestation of rheumatological and metabolic disease, congenital immunodeficiency, and haematological malignancy. Precise diagnosis of the underlying cause is essential in planning treatment, as well as for genetic counselling. The evidence base for treatment is poor. Some forms of PAP respond well to whole-lung lavage, and autoimmune PAP, which is much commoner in adults, responds to inhaled or subcutaneous GM-CSF. Emerging therapies based on studies in murine models of PAP include stem-cell transplantation for GM-CSF receptor mutations.Educational aimsTo understand when to suspect that a child has pulmonary alveolar proteinosis (PAP) and how to confirm that this is the cause of the presentation.To show that PAP is an umbrella term for conditions characterised by alveolar filling by normal or abnormal surfactant, and that this term is the start, not the end, of the diagnostic journey.To review the developmental differences in the spectrum of conditions that may cause PAP, and specifically to understand the differences between causes in adults and children.To discuss when to treat PAP with whole-lung lavage and/or granulocyte–macrophage colony-stimulating factor, and review potential promising new therapies.

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Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia

Cited by 30 publications

References 38 publications

Inborn errors of immunity—recent advances in research on the pathogenesis

Inborn errors of immunity—recent advances in research on the pathogenesis

Beyond “Big Eaters”: The Versatile Role of Alveolar Macrophages in Health and Disease

Pulmonary alveolar proteinosis in children

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