Patient with AR-CGD Presenting with Disseminated Aspergillosis During Pregnancy Associated with Suppression of the Th17 Axis

Author:

Utkucan Acar, Gloria Sheng, Terrie Ahn, Lisa Kohn, Maria Garcia Lloret, Manish Butte

Full conference title:

American Academy of Allergy, Asthma and Immunology Annual Meeting 2022

Date: 25 February 2022

Abstract:

Rationale:

Pregnancy is associated with suppression of the Th17 axis to induce tolerance to the fetus. Here, we report a patient with chronic granulomatous disease (CGD) presenting with disseminated Aspergillosis during pregnancy.

Methods:

Genetic sequencing was performed at GeneDx. p47-phox expression was assessed by immunoblot. T helper cell phenotyping was performed via flow cytometry and intracellular cytokine staining.

Results:

35-year-old G2P1 female presented at 36 weeks of gestation with fever, lower back pain, and weight loss. Infectious workup revealed vertebral osteomyelitis and CNS, breast, mediastinal abscesses due to Aspergillus fumigatus. Histograms from multiple dihydrorhodamine (DHR) tests were consistent with autosomal recessive (AR) CGD. Targeted sequencing revealed a single heterozygous pathogenic variant (c.75_76delGT) in NCF1. Further analysis by immunoblot confirmed deficient p47-phox expression. The patient improved on long-term antifungal therapy with voriconazole and caspofungin and immunomodulation with interferon-gamma and G-CSF. T helper cell polarization shifted over time, demonstrating a 4.8-fold decrease in Th1/Th17 ratio and no significant change in Th1/Th2 ratio from 1 to 7 months postpartum.

Conclusions:

This is the first reported case of AR-CGD presenting as an invasive fungal infection during pregnancy. The Th17 axis is critical for controlling fungal infections including Aspergillus. We hypothesize that our patient’s susceptibility to disseminated Aspergillus in the setting of AR-CGD was augmented by a prolonged immunosuppressed state secondary to two pregnancies within 24 months. We confirmed her relative Th17 suppression in the immediate postpartum period and demonstrated recovery of the Th17 compartment 6 months later.

Abstract Number: 82

Conference Year: 2022

Link to conference website: https://plan.core-apps.com/aaaai2022/abstracts

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