Severe pulmonary vascular occlusive disease following bone marrow transplantation in Omenn syndrome

Patients with Omenn syndrome (OS) have hypomorphic RAG mutations and develop varying manifestations of severe combined immunodeficiency. It is not known which symptoms are caused directly by the RAG mutations and which depend on other polymorphic genes. Our current understanding of OS is limited by the lack of an animal model. In the present study, we identified a C57BL/10 mouse with a spontaneous mutation in, and reduced activity of, RAG1. Mice bred from this animal contained high numbers of memory-phenotype T cells and experienced hepatosplenomegaly and eosinophilia, had oligoclonal T cells, and demonstrated elevated levels of IgE, major symptoms of OS. Depletion of CD4 + T cells in the mice caused a reduction in their IgE levels. Hence these "memory mutant" mice are a model for human OS; many symptoms of their disease were direct results of the Rag hypomorphism and some were caused by malfunctions of their CD4 + T cells.

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“…responses from OS patients had variations from absent to normal compared with T cells from healthy volunteers (15)(16)(17)(18)(19)(20).…”

Section: Figurementioning

confidence: 97%

Homeostatically proliferating CD4+ T cells are involved in the pathogenesis of an Omenn syndrome murine model

et al. 2007

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“…1), but in general these T-cells are of oligoclonal origin with highly restricted T-cell receptor (TCR) heterogeneity [12,34]. Furthermore, the T-cells have very poor proliferative responses in vitro [4,5,7,27]. Frequently, they express the CD45RO isoform which is characteristic of primed/ memory cells, and show an activated phenotype (CD25 + /HLA-DR + ) [6,37].…”

Section: Immunologymentioning

confidence: 99%

“…Most often it concerns aseptic organitis, containing in®ltration of T-cells, histiocytes and eosinophils. The organitis contributes to life-threatening complications [2,5,12,21,35,46]. This condition is dicult to discern from opportunistic infections and may react on immunosuppressive medication [18,25].…”

Section: Pathologymentioning

confidence: 99%

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Reviewing Omenn syndrome

et al. 2001

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“…An infant with Omenn syndrome was found to have biventricular hypertrophy, impaired left ventricular systolic function, and severe sinus bradycardia, possibly secondary to endomyocardial disease caused by eosinophilia (Bruckmann et al 1991).…”

Section: Predominantly T Lineage Defects Omenn Syndromementioning

confidence: 99%

Cardiovascular abnormalities in primary immunodeficiency diseases

et al. 2015

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In recent years, increasing numbers of patients with primary immune deficiency (PID) are being recognized as also suffering from cardiovascular system (CVS) abnormalities. These CVS defects might be explained by infectious or autoimmune etiologies, as well as by the role of specific genes and the immune system in the development and function of CVS tissues. Here, we provide the first comprehensive review of the clinical, potentially pathogenic mechanisms, and the management of PID, as well as the associated immune and CVS defects. In addition to some well-known associations of PID with CVS abnormalities, such as DiGeorge syndrome and CHARGE anomaly, we describe the cardiac defects associated with Omenn syndrome, calcium channel deficiencies, DNA repair defects, common variable immunodeficiency, Roifman syndrome, various neutrophil/macrophage defects, FADD deficiency, and HOIL1 deficiency. Moreover, we detail the vascular abnormalities recognized in chronic mucocutaneous candidiasis, chronic granulomatous disease, Wiskott-Aldrich syndrome, Schimke immuno-osseus dysplasia, hyper-IgE syndrome, MonoMAC syndrome, and X-linked lymphoproliferative disease. In conclusion, the expanding spectrum of PID requires increased alertness to the possibility of CVS involvement as an important contributor to the diagnosis and management of these patients.

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Severe pulmonary vascular occlusive disease following bone marrow transplantation in Omenn syndrome

Cited by 20 publications

References 21 publications

Homeostatically proliferating CD4+ T cells are involved in the pathogenesis of an Omenn syndrome murine model

Homeostatically proliferating CD4+ T cells are involved in the pathogenesis of an Omenn syndrome murine model

Reviewing Omenn syndrome

Cardiovascular abnormalities in primary immunodeficiency diseases

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