This study analyzed 16 patients with Hyper IgE Syndrome from a hospital in South India between 2018-2022. Five distinct genetic mutations were identified in 6 patients who underwent genetic testing, including mutations in STAT3, DOCK8, LAMTOR2, CARD11, IL2ra, and PEPD genes. Patients experienced recurrent infections like pneumonia and abscesses. Median age was 36 months and most common manifestations were eczema, rashes, skeletal abnormalities, and facial dysmorphism. Two patients died from infections. The study helps characterize the clinical features and genetic causes of Hyper IgE Syndrome in the region.

1. Ritasman Baisya (1) , Ramesh Manthri (2) , Phani Kumar (3) , Liza Rajasekhar (4)
1- Assistant Professor , 2 - Research Coordinator , 3- Associate Professor , 4 - Professor
Clinical Immunology and Rheumatology, Nizam's Institute of Medical Sciences. Telangana, India
Introduction
Clinical spectrum of Hyper IgE syndrome - a study from a tertiary care hospital in South India
Representative Figures
We report four cases ( out of six ) of previously reported mutations in patients with HIES , with two mutation were of uncertain significance , PEPD
and IL2ra mutation was unique in this case series
Spectrum of infection was similar to other cohorts. ( USIDNET / Indian cohort ( from nine centers) , no mycobacteria infection in these patients.
Variable Frequency (n-
16)
Percentage
Median age 36 months (
50.5)
-
Gender (M/F) 11/5 -
Infection
1. Pneumonia
2. Abscess
3. URTI
4. CSOM
5. Candida
6. Fatal infection
11
6
2
1
2
4
68.7
37.5
12.5
6.3
12.5
25
Cutaneous
1. Eczema
2. Non-specific papular rash
7
5
43.7
31.3
Skeletal abnormality 4 25
Facial dysmorphism 6 37.5
Median NIHSS 24 ( 14.5) -
IgE > 2500 11 68.7
Low IgG/IgM/IgA 1 each 6.3
⮚ In the study period 500 patients were screened for IEI. Hyper IgE syndrome was noted in 16 . Clinical exome sequence was done in 6 patients
⮚ The median duration of follow-up of these patients is 34.5 months with range from 5-96 months . Till last follow-up 11 patients are alive, two died and
3 are lost to follow up
Table 1 – Clinical & immunologic characteristics
Mutations were identified in the following genes ( 5/6 patients sent for genetic testing , mutatios
came pathogenic )
1. STAT3 ,Exon 14 variant, c.1268G>A, Heterozygous, AD ,Likely Pathogenic)
2. DOCK8, Exons 8 to 28,ENST00000453981.1,AR , Pathogenic)
3. LAMTOR2 , Exon 4, c.330C>A (p.Cys110Ter), Heterozygous, Variant of
Uncertain Significance))
4. CARD11, Exon 5,variant c.601A>C (p.Asn201His), uncertain significance
5. IL2ra ,Intron 3. c368-2A>G (3’ splice site) ,Homozygous, Pathogenic
6. PEPD , Intron 9,varient c.671+1G>A (5’ Splice variant),Homozygous, Pathogenic
⮚ Sites of abscess - cutaneous (4) , scalp , calf muscle .
⮚ Arthritis , cytopenia in IL2ra mutation patient
⮚ Predominant non-infectious cutaneous manifestation in PEPD
mutation
⮚ Median ( IQR) NIHS in survivors– 21(9)
⮚ Median NIHS in non-survivors – 19 (29)
⮚ Decreased CD4 , CD8 T cell in CARD11 mutation
⮚ Decreased CD3 T , CD4 T cell in DOCK8 mutation
T-B Subset analysis Number
(n=16)
CD3 T low 3
CD4 T low 5
CD8 T low 1
CD19 B low 1
3
2
8
3
lfu no yes yes,symptomatic
Count of survival
Patient with PEPD mutation – facial dysmorphism , skin itchy papules Patient with STAT3 mutation – mutliple cutaneous abscess , mild facial dysmorphism
1. Bergerson JRE, Freeman AF. An Update on Syndromes with a Hyper-IgE Phenotype. Immunol Allergy Clin North Am. 2019 Feb;39(1):49-61
2. Y. Gernez et al.Autosomal dominant hyper-IgE syndrome in the USIDNET registry .J Allergy Clin Immunol Pract , 2018
3. Saikia B, Rawat A, Minz RW, Suri D, Pandiarajan V, Jindal A, Sahu S, Karim A, Desai M, Taur PD et al . Clinical Profile of Hyper-IgE Syndrome in India. Front Immunol. 2021 Feb 26;12:626593
4. Baisya, R., Ranganath, P. Rajasekhar, L. PEPD-Related Prolidase Deficiency Presenting as Hyper-immunoglobulin E Syndrome. J Clin Immunol 42, 892–897 (2022)..
Results
The Hyper-IgE ( HIES ) syndrome phenotype includes -
recurrent infections associated with recurrent eczema and
elevated serum IgE.(1) Many different genetic mutations can
have HIES phenotype leading to overlapping clinical and
immunological features.
Objectives
To study the clinical , immunological features and genetic
mutations associated with HIES phenotype
Methods
⮚ Hospital based retrospective observational study
⮚ Data of all patients screened for Inborn errors of Immunity (IEI)
between 2018 and -November 2022 were reviewed. Clinical diagnosis,
Clinical and Immunological data was noted. Where available , (after
2019) , clinical exome sequencing data was retrieved.
⮚ Follow up data were collected either from OP record or by telephonic
consultation
Conclusions
Reference