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Aspergillosis and Mucormycosis
Published in Rebecca A. Cox, Immunology of the Fungal Diseases, 2020
Alayn R. Waldorf, Richard D. Diamond
Myeloperoxidase deficiency may unmask other mechanisms for hyphal damage. Hyphal damage by monocytes from patients with complete hereditary myeloperoxidase deficiency presumably occurs because of alternative oxidative or nonoxidative antihyphal mechanisms.67These differences in ability to damage Rhizopus, but not Aspergillus hyphae, also may explain, in part, the predisposition seen by these patients for aspergillosis but not mucormycosis. In vivo, alternative mechanisms to the myeloperoxidase system inducing hyphal damage are particularly relevant because granule-associated myeloperoxidase is lost during differentiation of monocytes into macrophages. This suggests that oxidative microbicidal products independent of the myeloperoxidase system may be important.70 These oxidative products may include superoxide anion, hydrogen peroxide,70–72 singlet oxygen, and hydroxyl radicals.71–74 Singlet oxygen may be important in damaging Rhizopus hyphae, as quenchers of singlet oxygen inhibited monocyte damage,67 but they also antagonize the effects of hypochlorous acid, a product of the myeloperoxidase system.73,74
Inflammation
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
Absolute deficiency of glucose-6-phosphate dehydrogenase is also associated with symptoms of chronic granulomatous disease. The clinical manifestation of this condition is similar to the disease induced by bacteria, although the onset of infectious lesions mostly occurs in late childhood or adolescence.20,156 The microorganisms involved are E. coli, S. aureus and K. pneumoniae. The lack of H2O2 causes the persistence of pyogenic microorganisms and chronic infection.20 In contrast to chronic granulomatous condition and glucose 6-phosphate dehydrogenase deficiency, patients with myeloperoxidase deficiency rarely develop infections. The phagocytes of myeloperoxidase-deficient patients show a characteristic bactericidal abnormality in vitro. There is a delay in bacteria killing, but by about 4 h almost all ingested microorganisms are killed.17,18
Host Defense I: Non-specific Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
Myeloperoxidase deficiency impairs function of the MPO-H2O2-halide system. These patients are most often asymptomatic, but may have increased susceptibility to fungal infections, particularly Candidiasis.
Clinical Profile and Outcomes of Primary Immunodeficiency and Malignancy in Childhood at a Tertiary Oncology Center in Developing Country
Published in Pediatric Hematology and Oncology, 2022
Derya Özyörük, Zeliha Güzelküçük, Ayse Metin, Suna Emir, Arzu Yazal Erdem, Dilek Kacar, Ayca Koca Yozgat, Can Baris Aker, Selma Çakmakçı, Sonay Incesoy Özdemir, Neriman Sari, Meriç Kaymak Cihan, Namık Yasar Özbek, İnci Ergürhan İlhan
The retinoblastoma tumor suppressor protein plays important roles in the control of the cell division cycle. In addition, it is critical for hematopoietic stem and progenitor cell function, localization, and differentiation.22 So far, congenital or acquired myeloperoxidase deficiency have not been reported in patient with retinoblastoma in the English literature. In the present study, the automatic differential count of patient with retinoblastoma showed normal white blood cell count and low absolute neutrophil count together with increased count of “large unstained cells.” The peripheral smear showed no abnormality. Flow cytometric analysis of peripheral blood revealed myeloperoxidase deficiency. Genetic analysis confirmed myeloperoxidase deficiency. We suggest that it should keep in mind in patient who have populations of “large unstained cells” together with normal white blood cells but low absolute neutrophils counts in automatic differential counts.
SEIFEM 2017: from real life to an agreement on the use of granulocyte transfusions and colony-stimulating factors for prophylaxis and treatment of infectious complications in patients with hematologic malignant disorders
Published in Expert Review of Hematology, 2018
Alessandro Busca, Simone Cesaro, Luciana Teofili, Mario Delia, Chiara Cattaneo, Marianna Criscuolo, Francesco Marchesi, Nicola Stefano Fracchiolla, Caterina Giovanna Valentini, Francesca Farina, Roberta Di Blasi, Lucia Prezioso, Angelica Spolzino, Anna Candoni, Maria Ilaria del Principe, Luisa Verga, Annamaria Nosari, Franco Aversa, Livio Pagano
Chemotactic activity is reduced in myeloproliferative disorders, particularly in patients with polycythemia vera and chronic myeloid leukemia (CML) [23]. Myeloperoxidase deficiency and impaired ROS production may be responsible for a decreased phagocytic activity in CML and primary myelofibrosis [23,24].
Generalized pustular psoriasis is a disease distinct from psoriasis vulgaris: evidence and expert opinion
Published in Expert Review of Clinical Immunology, 2022
Hervé Bachelez, Jonathan Barker, A. David Burden, Alexander A. Navarini, James G. Krueger
Additional genetic components of GPP have since been identified, providing evidence for the genetic basis of disease in patients without alterations in IL36RN. In Europe, approximately 11% of patients with GPP carry a mutation in AP1S3, which encodes a subunit of the adaptor protein 1 complex [41], with some of these patients also having IL36RN mutations [114]. Alterations in AP1S3 result in upregulated IL-1 signaling and overexpression of IL-36 cytokines (ligands), and inhibited keratinocyte autophagy [114,115], suggesting a likely role in GPP pathology. AP1S3 mutations have been reported in other pustular diseases, including PPP, ACH, and acute generalized exanthematous pustulosis (AGEP) [116]. Studies have described mutations in CARD14 in small proportions of Chinese and Japanese patients with GPP, usually with concomitant PV [117,118]; however, a family with GPP showing autosomal dominant inheritance of CARD14 mutations in the absence of PV has also been reported [119]. Given the scarcity of evidence currently available, the pathogenicity of CARD14 mutations has not yet been established for GPP, with murine models showing a PV-like rather than a GPP-like phenotype [120,121], whereas IL36RN transgenic mice have a GPP-like phenotype [100]. The correlation between CARD14 mutations and the onset of GPP, in the absence of PV, therefore remains to be adequately defined. More recently, mutations in MPO (encoding myeloperoxidase) have also been identified as a driver of pustular disease, including GPP [122,123]. The mechanism for pathogenesis caused by myeloperoxidase deficiency has yet to be fully elucidated, although modifications in the activity of neutrophils and of proteases involved in the cleavage of IL-36 precursors to produce active IL-36 agonists have been reported [122,123]. In addition, an LOF heterozygous mutation in SERPINA3 (encoding a serine protease inhibitor) was identified in two patients with GPP and ‘significantly associated with GPP’ [124]. As more genetic factors are identified, it becomes increasingly clear that the underlying cause of pustular disease, particularly GPP, is different from that of psoriatic plaques, and while there may be different genetic causes in individuals, it is striking that all pathways identified so far bisect at the level of IL-36.