HIES in south india

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