Clinical, Immunological, and Molecular Profile of Chronic Granulomatous Disease: A Multi-Centric Study of 236 Patients From India

• DOI: 10.3389/fimmu.2021.625320
• Publication Date: 2021-02-25T04:37:01Z
• Authors: Amit Rawat; Pandiarajan Vignesh; Murugan Sudhakar; Madhubala Sharma; Deepti Suri; Ankur Jindal; Anju Gupta; Jitendra Kumar Sh...; Sathish Kumar Log...; Gurjit Kaur; Sanchi Chawla; Pratap Kumar Patra; Alka Khadwal; Biman Saikia; Ranjana Walker Minz; Vaishali Aggarwal; Prasad Taur; Ambreen Pandrowala; Vijaya Gowri; Mukesh Desai; Manasi Kulkarni; Gauri Hule; Umair Bargir; Priyanka Kambli; Manisha Madkaikar; Sagar Bhattad; Chetan Ginigeri; Harish Kumar; Ananthvikas Jayaram; Deenadayalan Muni...; Meena Sivasankaran; Revathi Raj; Ramya Uppuluri; Fouzia Na; Biju George; Harsha Prasada La...; Manas Kalra; Anupam Sachdeva; Shishir Seth; Tapas Sabui; Aman Gupta; Karin van Leeuwen; Martin de Boer; Koon Wing Chan; Kohsuke Imai; Osamu Ohara; Shigeaki Nonoyama; Yu Lung Lau; Surjit Singh
• Keywords: Male; 0301 basic medicine; Immunology; India; Granulomatous Disease, Chronic; Chronic Granulomatous Disease; 03 medical and health sciences; Phagocytosis; Lymphadenitis; Humans; Bacillus Calmette Guerin; Skin; Hematopoietic Stem Cell Transplantation; Infant; NADPH Oxidases; Mycobacterium tuberculosis; Pneumonia; RC581-607; Survival Analysis; 3. Good health; Child, Preschool; Mutation; NADPH Oxidase 2; Female; Immunologic diseases. Allergy

BackgroundChronic granulomatous disease (CGD) is an inherited defect in phagocytic respiratory burst that results in severe and life-threatening infections in affected children. Single center studies from India have shown that proportion of autosomal recessive (AR) CGD is more than that reported from the West. Further, affected patients have high mortality rates due to late referrals and difficulties in accessing appropriate treatment. However, there is lack of multicentric collaborative data on CGD from India.ObjectiveTo describe infection patterns, immunological, and molecular features of CGD from multiple centers in India.MethodsA detailed proforma that included clinical and laboratory details was prepared and sent to multiple centers in India that are involved in the care and management of patients with inborn errors of immunity. Twelve centers have provided data which were later pooled together and analyzed.ResultsOf the 236 patients analyzed in our study, X-linked and AR-CGD was seen in 77 and 97, respectively. Male female ratio was 172:64. Median age at onset of symptoms and diagnosis was 8 and 24 months, respectively. Common infections documented include pneumonia (71.6%), lymphadenitis (31.6%), skin and subcutaneous abscess (23.7%), blood-stream infection (13.6%), osteomyelitis (8.6%), liver abscess (7.2%), lung abscess (2.9%), meningoencephalitis (2.5%), splenic abscess (1.7%), and brain abscess (0.9%). Forty-four patients (18.6%) had evidence of mycobacterial infection. Results of molecular assay were available for 141 patients (59.7%)—CYBB (44.7%) gene defect was most common, followed by NCF1 (31.9%), NCF2 (14.9%), and CYBA (8.5%). While CYBA variants were documented only in Southern and Western parts of India, a common dinucleotide deletion in NCF2 (c.835_836delAC) was noted only in North Indian population. Of the 174 patients with available outcome data, 67 (38.5%) had expired. Hematopoietic stem cell transplantation was carried out in 23 patients, and 12 are doing well on follow-up.ConclusionsIn India, proportion of patients with AR-CGD is higher as compared to Western cohorts, though regional differences in types of AR-CGD exist. Clinical profile and mortality rates are similar in both X-linked and AR-CGD. However, this may be a reflection of the fact that milder forms of AR-CGD are probably being missed.