# Clinical, Genetic, and Immunological Spectrum of CHAI and LATAIE Patients from a Tertiary Referral Centre in India

## TL;DR

This study explores the clinical and genetic features of two immune disorders, CHAI and LATAIE, in Indian patients, highlighting their similarities and differences.

## Contribution

The study provides a detailed clinical and molecular characterization of CHAI and LATAIE patients from India, identifying distinct immunological and genetic profiles.

## Key findings

- LATAIE patients showed higher consanguinity and more infections compared to CHAI patients.
- CHAI patients had a stronger family history and similar autoimmune features as LATAIE.
- Distinct T cell subset differences were observed between CHAI and LATAIE patients.

## Abstract

Primary immune regulatory disorders (PIRDs) are a group of conditions characterised by a loss of immune tolerance. Two such disorders, CHAI and LATAIE, share common molecular mechanisms, leading to significant clinical overlap. Here, we report demographic, clinical, immunological, and molecular findings in 29 patients referred from different parts of India with a diagnosis of CHAI or LATAIE. LATAIE patients demonstrated a higher prevalence of consanguinity, while CHAI patients more often had a positive family history. Both disorders presented with overlapping clinical features, predominately autoimmune cytopenias, benign lymphoproliferation, and inflammatory bowel disease (IBD). However, the incidence of recurrent infections, otitis media, bronchiectasis, and hypogammaglobulinemia was higher among LATAIE patients as compared to CHAI. Flow cytometry analysis revealed significant differences in T cell subsets, particularly in percentages of CD4+ naïve cells and T regulatory cells (Treg), between the two disorders. B cell abnormalities were also observed. Molecular diagnosis was achieved using targeted or clinical exome sequencing, and specific protein expression was employed to validate the novel variants.