Abstract
We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis.
| Original language | English |
|---|---|
| Pages (from-to) | 130 |
| Journal | Frontiers in Immunology |
| Volume | 10 |
| DOIs | |
| Publication status | Published - Feb 14 2019 |
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First Case of Patient With Two Homozygous Mutations in MYD88 and CARD9 Genes Presenting With Pyogenic Bacterial Infections, Elevated IgE, and Persistent EBV Viremia. / Chiriaco, Maria; Di Matteo, Gigliola; Conti, Francesca; Petricone, Davide; De Luca, Maia; Di Cesare, Silvia; Cifaldi, Cristina; De Vito, Rita; Zoccolillo, Matteo; Serafinelli, Jessica; Poerio, Noemi; Fraziano, Maurizio; Brigida, Immacolata; Cardinale, Fabio; Rossi, Paolo; Aiuti, Alessandro; Cancrini, Caterina; Finocchi, Andrea.
In: Frontiers in Immunology, Vol. 10, 14.02.2019, p. 130.Research output: Contribution to journal › Article
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TY - JOUR
T1 - First Case of Patient With Two Homozygous Mutations in MYD88 and CARD9 Genes Presenting With Pyogenic Bacterial Infections, Elevated IgE, and Persistent EBV Viremia
AU - Chiriaco, Maria
AU - Di Matteo, Gigliola
AU - Conti, Francesca
AU - Petricone, Davide
AU - De Luca, Maia
AU - Di Cesare, Silvia
AU - Cifaldi, Cristina
AU - De Vito, Rita
AU - Zoccolillo, Matteo
AU - Serafinelli, Jessica
AU - Poerio, Noemi
AU - Fraziano, Maurizio
AU - Brigida, Immacolata
AU - Cardinale, Fabio
AU - Rossi, Paolo
AU - Aiuti, Alessandro
AU - Cancrini, Caterina
AU - Finocchi, Andrea
PY - 2019/2/14
Y1 - 2019/2/14
N2 - We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis.
AB - We described for the first time a female patient with the simultaneous presence of two homozygous mutations in MYD88 and CARD9 genes presenting with pyogenic bacterial infections, elevated IgE, and persistent EBV viremia. In addition to defective TLR/IL1R-signaling, we described novel functional alterations into the myeloid compartment. In particular, we demonstrated a defective production of reactive oxygen species exclusively in monocytes upon E. coli stimulation, the inability of immature mono-derived DCs (iDCs) to differentiate into mature DCs (mDCs) and the incapacity of mono-derived macrophages (MDMs) to resolve BCG infection in vitro. Our data do not provide any evidence for digenic inheritance in our patient, but rather for the association of two monogenic disorders. This case illustrates the importance of using next generation sequencing (NGS) to determine the most accurate and early diagnosis in atypical clinical and immunological phenotypes, and with particular concern in consanguineous families. Indeed, besides the increased susceptibility to recurrent invasive pyogenic bacterial infections due to MYD88 deficiency, the identification of CARD9 mutations underline the risk of developing invasive fungal infections emphasizing the careful monitoring for the occurrence of fungal infection and the opportunity of long-term antifungal prophylaxis.
U2 - 10.3389/fimmu.2019.00130
DO - 10.3389/fimmu.2019.00130
M3 - Article
C2 - 30837984
VL - 10
SP - 130
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
ER -