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Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China

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Abstract

Purpose

Activated phosphoinositide 3-kinase δ syndrome (APDS) is a primary immunodeficiency first described in 2013, which is caused by gain-of-function mutations in PIK3CD or PIK3R1, and characterized by recurrent respiratory tract infections, lymphoproliferation, herpesvirus infection, autoimmunity, and enteropathy. We sought to review the clinical phenotypes, immunological characteristics, treatment, and prognosis of APDS in a large genetically defined Chinese pediatric cohort.

Methods

Clinical records, radiology examinations, and laboratory investigations of 40 APDS patients were reviewed. Patients were contacted via phone call to follow up their current situation.

Results

Sinopulmonary infections and lymphoproliferation were the most common complications in this cohort. Three (10.3%) and five (12.5%) patients suffered localized BCG-induced granulomatous inflammation and tuberculosis infection, respectively. Twenty-seven patients (67.5%) were affected by autoimmunity, while malignancy (7.5%) was relatively rare to be seen. Most patients in our cohort took a combined treatment of anti-infection prophylaxis, immunoglobulin replacement, and immunosuppressive therapy such as glucocorticoid or rapamycin administration. Twelve patients underwent hematopoietic stem cell transplantation (HSCT) and had a satisfying prognosis.

Conclusion

Clinical spectrum of APDS is heterogeneous. This cohort’s high incidence of localized BCG-induced granulomatous inflammation and tuberculosis indicates Mycobacterial susceptibility in APDS patients. Rapamycin is effective in improving lymphoproliferation and cytopenia. HSCT is an option for those who have severe complications and poor response to other treatments.

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Data Availability

The data that support the findings of this study is available from the corresponding author, XD.Z., upon reasonable request.

Code Availability

Not applicable.

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Acknowledgements

We thank the support, cooperation, and trust of patients, donors, and their families.

Funding

This work was supported by the Natural Science Foundation of China (Grant Numbers 81974255 and 81620108014).

Author information

Authors and Affiliations

  1. Department of Pediatric Research Institute; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children’s Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Luyao Qiu, Wenjing Tang, Junjie Chen, Lina Zhou, Zhiyong Zhang, Yunfei An, Xuemei Tang & Xiaodong Zhao

  2. Chongqing Key Laboratory of Child Infection and Immunity, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Luyao Qiu, Yanping Wang, Qiuyun Yang, Ting Zeng, Junjie Chen, Xuemei Chen, Liang Zhang, Lina Zhou & Xiaodong Zhao

  3. Department of Rheumatology and Immunology, Children’s Hospital of Chongqing Medical University, Chongqing, 400014, China

    Luyao Qiu, Wenjing Tang, Junjie Chen, Lina Zhou, Zhiyong Zhang, Yunfei An, Xuemei Tang & Xiaodong Zhao

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  1. Luyao Qiu
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Contributions

XD.Z. designed this study and corrected the manuscript. LY.Q. collected clinical data, contacted patients, performed experiments, and drafted the manuscript. YP.W., WJ.T., QY.Y., XM.C., T.Z., JJ.C., and LN.Z. performed experiments. L.Z. provided help in conducting this research. ZY.Z., YF.A., and XM.T. offered some crucial clinical data.

Corresponding author

Correspondence to Xiaodong Zhao.

Ethics declarations

Ethics Approval

The study was performed following the Declaration of Helsinki and improved by the ethics committee of Children’s Hospital of Chongqing Medical University (Chongqing, China). Written informed consents for involvement in this study were provided by parents.

Consent to Participate

Written informed consent was obtained from individual or guardian participants.

Consent for Publication

Written informed consent was obtained from individual or guardian participants.

Conflict of Interest

The authors declare no competing interests.

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Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Tables 1 and 2

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Fig. S1

Head MRI of patient 9 demonstrated extensive nodules and small ring-like enhancements of varying sizes in the cerebrum, cerebello and brainstem (a, b, c) and patchy hyperintensity under part of the cortex, indicating tuberculosis meningitis. a transverse section of T1 enhanced sequence; b coronal section of T1 enhanced sequence; c median sagittal section of T1 enhanced sequence; d transverse section of T2-FLAIR (PNG 745 kb)

High resolution image (EPS 2911 kb)

Fig. S2

Summary of infective pathogens of APDS patients (PNG 226 kb)

High resolution image (EPS 1371 kb)

Fig. S3

Absolute count of lymphocyte subsets in APDS patients. S: supportive treatment only; R: rapamycin; G: glucocorticoid; *p<0.05 (PNG 367 kb)

High resolution image (EPS 7779 kb)

Fig. S4

Relative count of lymphocyte subsets in APDS patients. S: supportive treatment only; R: rapamycin; G: glucocorticoid; *p<0.05; **p<0.005 (PNG 388 kb)

High resolution image (EPS 7679 kb)

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Qiu, L., Wang, Y., Tang, W. et al. Activated Phosphoinositide 3-Kinase δ Syndrome: a Large Pediatric Cohort from a Single Center in China. J Clin Immunol 42, 837–850 (2022). https://doi.org/10.1007/s10875-022-01218-4

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  • DOI: https://doi.org/10.1007/s10875-022-01218-4

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