TY - JOUR
T1 - Clinical and Genetic Profile of X-Linked Agammaglobulinemia
T2 - A Multicenter Experience From India
AU - Rawat, Amit
AU - Jindal, Ankur Kumar
AU - Suri, Deepti
AU - Vignesh, Pandiarajan
AU - Gupta, Anju
AU - Saikia, Biman
AU - Minz, Ranjana W.
AU - Banday, Aaqib Zaffar
AU - Tyagi, Rahul
AU - Arora, Kanika
AU - Joshi, Vibhu
AU - Mondal, Sanjib
AU - Shandilya, Jitendra Kumar
AU - Sharma, Madhubala
AU - Desai, Mukesh
AU - Taur, Prasad
AU - Pandrowala, Ambreen
AU - Gowri, Vijaya
AU - Sawant-Desai, Sneha
AU - Gupta, Maya
AU - Dalvi, Aparna Dhondi
AU - Madkaikar, Manisha
AU - Aggarwal, Amita
AU - Raj, Revathi
AU - Uppuluri, Ramya
AU - Bhattad, Sagar
AU - Jayaram, Ananthvikas
AU - Lashkari, Harsha Prasad
AU - Rajasekhar, Liza
AU - Munirathnam, Deenadayalan
AU - Kalra, Manas
AU - Shukla, Anuj
AU - Saka, Ruchi
AU - Sharma, Rajni
AU - Garg, Ravinder
AU - Imai, Kohsuke
AU - Nonoyama, Shigeaki
AU - Ohara, Osamu
AU - Lee, Pamela P.
AU - Chan, Koon Wing
AU - Lau, Yu Lung
AU - Singh, Surjit
N1 - Funding Information:
We thankfully acknowledge Sudhir Gupta and Abha Gupta, Foundation for Primary Immunodeficiencies, USA; State Governments of Punjab, Haryana, Madhya Pradesh, Delhi, Himachal Pradesh, Karnataka, Kerala, Tamil Nadu, and West Bengal; Kusum Arora Memorial Trust, Sukhmani Foundation; Pediatric Medical Support Society; God?s Child Foundation and Veeranwali Foundation for their generous financial support to a large number of children in this cohort. This financial support has helped in providing regular IVIG therapy to some of the patients in the present cohort. We acknowledge Geeta Govindaraj from Government Medical College, Kozhikode, Kerala for providing the number of patients with suspected XLA diagnosed at their centers. We do acknowledge India Council of Medical Research (ICMR), New Delhi, India, and Department of Health Research, Ministry of Health and Family Welfare, Government of India, New Delhi, India for funding (vide Grant No. GIA/48/2014-DHR). However, the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© Copyright © 2021 Rawat, Jindal, Suri, Vignesh, Gupta, Saikia, Minz, Banday, Tyagi, Arora, Joshi, Mondal, Shandilya, Sharma, Desai, Taur, Pandrowala, Gowri, Sawant-Desai, Gupta, Dalvi, Madkaikar, Aggarwal, Raj, Uppuluri, Bhattad, Jayaram, Lashkari, Rajasekhar, Munirathnam, Kalra, Shukla, Saka, Sharma, Garg, Imai, Nonoyama, Ohara, Lee, Chan, Lau and Singh.
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1/15
Y1 - 2021/1/15
N2 - Background: There is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India. Methods: Data on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria. Results: We received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 ‘definite XLA’ and eight ‘probable/possible XLA’). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. Pseudomonas aeruginosa was the commonest bacterial pathogen identified followed by Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae. Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in BTK gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14–19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients. Conclusion: There was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge
AB - Background: There is paucity of literature on XLA from developing countries. Herein we report the clinical and molecular profile and outcome in a multicenter cohort of patients with XLA from India. Methods: Data on XLA from all regional centers supported by the Foundation for Primary Immunodeficiency Diseases (FPID), USA and other institutions providing care to patients with PIDs were collated. Diagnosis of XLA was based on European Society for Immunodeficiencies (ESID) criteria. Results: We received clinical details of 195 patients with a provisional diagnosis of XLA from 12 centers. At final analysis, 145 patients were included (137 ‘definite XLA’ and eight ‘probable/possible XLA’). Median age at onset of symptoms was 12.0 (6.0, 36.0) months and median age at diagnosis was 60.0 (31.5, 108) months. Pneumonia was the commonest clinical manifestation (82.6%) followed by otitis media (50%) and diarrhea (42%). Arthritis was seen in 26% patients while 23% patients developed meningitis. Bronchiectasis was seen in 10% and encephalitis (likely viral) in 4.8% patients. Pseudomonas aeruginosa was the commonest bacterial pathogen identified followed by Streptococcus pneumoniae, Staphylococcus aureus and Klebsiella pneumoniae. Molecular analysis revealed 86 variants in 105 unrelated cases. Missense variants in BTK gene were the most common (36%) followed by frameshift (22%) and nonsense variants (21%). Most pathogenic gene variants (53%) were clustered in the distal part of gene encompassing exons 14–19 encoding for the tyrosine kinase domain. Follow-up details were available for 108 patients. Of these, 12% had died till the time of this analysis. The 5-year and 10-year survival was 89.9% and 86.9% respectively. Median duration of follow-up was 61 months and total duration of follow-up was 6083.2 patient-months. All patients received intravenous immunoglobulin (IVIg) replacement therapy. However, in many patients IVIg could not be given at recommended doses or intervals due to difficulties in accessing this therapy because of financial reasons and lack of universal health insurance in India. Hematopoietic stem cell transplant was carried out in four (2.8%) patients. Conclusion: There was a significant delay in the diagnosis and facilities for molecular diagnosis were not available at many centers. Optimal immunoglobulin replacement is still a challenge
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U2 - 10.3389/fimmu.2020.612323
DO - 10.3389/fimmu.2020.612323
M3 - Article
AN - SCOPUS:85100083622
SN - 1664-3224
VL - 11
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 612323
ER -
