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Clinical Profile of Hyper-IgE Syndrome in India

Authors :
Venkateswaran Vellaichamy Swaminathan
Revathi Raj
Manas Kalra
Ramya Uppuluri
Amit Rawat
Harsha Prasada Lashkari
Aparna Dalvi
Gladys Cyril
Mukesh Desai
Sagar Bhattad
Adil Karim
Reetika Mallik Yadav
Anuj Shukla
Ranjana W. Minz
Ankur Kumar Jindal
Smrity Sahu
Vijaya Gowri
Harish Kumar
Biman Saikia
Geeta Madathil Govindaraj
Surjit Singh
Ambreen Pandrowala
Manisha Madkaikar
Prasad Taur
Vignesh Pandiarajan
Deepti Suri
Source :
Frontiers in Immunology, Frontiers in Immunology, Vol 12 (2021)
Publication Year :
2020

Abstract

Introduction:Hyper-IgE Syndrome (HIES) is a rare inborn error of immunity (IEI) characterized by a constellation of symptoms related to susceptibility toStaphylococcalskin and pulmonary infections, eczema, raised serum IgE (>2,000 IU/ml), craniofacial anomalies, and recurrent bone fractures. Data on HIES from the Indian subcontinent is scarce and restricted to small case series and case reports. This is the first compilation of national data on HIES.Materials and Methods:A total 103 cases clinically diagnosed and treated as HIES were analyzed from nine centers. Cases with clinical and/or molecular diagnosis of DOCK8 deficiency were not included. Patients were divided into two groups: group I for whom a heterozygous rare variant of STAT3 was identified, and group II, with clinical features similar to those of AD STAT3 deficiency, but without any genetic diagnosis.Results:Genetic diagnosis was available in 27 patients (26.2%) and all harbored rare variants in the STAT3 gene. Majority of these STAT3 HIES patients presented with recurrent skin abscesses (77.7%) or pneumonia (62.9%) or both (59.2%). Other features included eczema (37%), candidiasis (55.5%), facial dysmorphism (55.5%), recurrent fractures (11.1%), and retained primary teeth (7.4%).Mycobacterialinfections were seen in a significant 18.5%. Mortality was seen in three subjects (11.1%). A similar trend in the clinical presentation was observed when all the 103 patients were analyzed together. Twenty percent of patients without a rare variant in the STAT3 gene had an NIH score of ≥40, whereas, 51.9% of STAT3 HIES subjects had scores below the cut off of ≥40. TH17 cell numbers were low in 10/11 (90.9%) STAT3 HIES tested. Rare variants observed were 8 in exon 21; 8 in exon 13; 3 in exon 10; 2 in exon 15, and one each in exon 6, 16, 17, 19, 22, and splice site downstream of exon 12. Seven variants were novel and included F174S, N567D, L404Sfs*8, G419 =, M329K, T714I, R518X, and a splice site variant downstream of exon 12.Conclusions:The report includes seven novel STAT3 variants, including a rare linker domain nonsense variant and a CC domain variant.Mycobacterialdiseases were more frequent, compared to western literature.

Details

ISSN :
16643224
Volume :
12
Database :
OpenAIRE
Journal :
Frontiers in immunology
Accession number :
edsair.doi.dedup.....109ec5544c44d415d0f2920e11e933c3