Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India.

Autor:	Rawat A; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Jindal AK; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Suri D; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Vignesh P; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Gupta A; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Saikia B; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Minz RW; Department of Immunopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Banday AZ; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Tyagi R; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Arora K; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Joshi V; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Mondal S; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Shandilya JK; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Sharma M; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Desai M; Department of Immunology, B. J. Wadia Hospital, Mumbai, India., Taur P; Department of Immunology, B. J. Wadia Hospital, Mumbai, India., Pandrowala A; Bone Marrow Transplant Unit, B. J. Wadia Hospital, Mumbai, India., Gowri V; Department of Immunology, B. J. Wadia Hospital, Mumbai, India., Sawant-Desai S; Department of Pediatric Immunology and Leukocyte Biology, ICMR-National Institute of Immunohematology, K.E.M Hospital, Mumbai, India., Gupta M; Department of Pediatric Immunology and Leukocyte Biology, ICMR-National Institute of Immunohematology, K.E.M Hospital, Mumbai, India., Dalvi AD; Department of Pediatric Immunology and Leukocyte Biology, ICMR-National Institute of Immunohematology, K.E.M Hospital, Mumbai, India., Madkaikar M; Department of Pediatric Immunology and Leukocyte Biology, ICMR-National Institute of Immunohematology, K.E.M Hospital, Mumbai, India., Aggarwal A; Department of Clinical Immunology and Rheumatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India., Raj R; Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India., Uppuluri R; Department of Pediatric Hematology, Oncology, Blood and Marrow Transplantation, Apollo Hospitals, Chennai, India., Bhattad S; Division of Pediatric Immunology and Rheumatology, Department of Pediatrics, Aster CMI Hospital, Bengaluru, India., Jayaram A; Neuberg Anand Reference Laboratory, Bengaluru, India., Lashkari HP; Department of Paediatrics, Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal, India., Rajasekhar L; Department of Clinical Immunology and Rheumatology, Nizam's Institute of Medical Sciences, Hyderabad, India., Munirathnam D; Department of Pediatric Hematology Oncology and Bone Marrow Transplant, Kanchi Kamakoti Childs Trust Hospital, Chennai, India., Kalra M; Department of Pediatric Hematology, Oncology and BMT, Sir Ganga Ram Hospital, New Delhi, India., Shukla A; Niruj Rheumatology Clinic, Ahmedabad, India., Saka R; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Sharma R; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Garg R; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India., Imai K; Department of Community Pediatrics, Perinatal and Maternal Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan., Nonoyama S; Department of Pediatrics, National Defense Medical College, Tokorozawa, Japan., Ohara O; Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan., Lee PP; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China., Chan KW; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China., Lau YL; Department of Paediatrics and Adolescent Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, China., Singh S; Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2021 Jan 15; Vol. 11, pp. 612323. Date of Electronic Publication: 2021 Jan 15 (Print Publication: 2020).
DOI:	10.3389/fimmu.2020.612323
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (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.)
Databáze:	MEDLINE
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