Clinical and Genetic Profile of X-Linked Agammaglobulinemia: A Multicenter Experience From India
| Autor: | Vijaya Gowri, Rajni Sharma, Osamu Ohara, Shigeaki Nonoyama, Ananthvikas Jayaram, Jitendra Kumar Shandilya, Biman Saikia, Anju Gupta, Pamela P. Lee, Sneha Sawant-Desai, Revathi Raj, Ambreen Pandrowala, Sanjib Mondal, Harsha Prasad Lashkari, Amit Rawat, Prasad Taur, Kanika Arora, Aparna Dalvi, Rahul Tyagi, Deenadayalan Munirathnam, Anuj Shukla, Manisha Madkaikar, Yu-Lung Lau, Ankur Kumar Jindal, Mukesh Desai, Ramya Uppuluri, Manas Kalra, Maya Gupta, Vibhu Joshi, Liza Rajasekhar, Sagar Bhattad, Deepti Suri, Kohsuke Imai, Ravinder Garg, Pandiarajan Vignesh, Amita Aggarwal, Koon Wing Chan, Ruchi Saka, Aaqib Zaffar Banday, Madhubala Sharma, Surjit Singh, Ranjana W. Minz |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
0301 basic medicine lcsh:Immunologic diseases. Allergy medicine.medical_specialty X-linked agammaglobulinemia Immunology India Neutropenia medicine.disease_cause 03 medical and health sciences 0302 clinical medicine Agammaglobulinemia Internal medicine hemic and lymphatic diseases intravenous immunoglobulin Streptococcus pneumoniae Agammaglobulinaemia Tyrosine Kinase Humans Immunology and Allergy Medicine neutropenia Child BTK gene Original Research Bronchiectasis business.industry Genetic Variation Immunoglobulins Intravenous Infant Genetic Diseases X-Linked Exons Genetic Profile Protein-Tyrosine Kinases medicine.disease 030104 developmental biology Otitis arthritis Child Preschool Primary immunodeficiency Female medicine.symptom business lcsh:RC581-607 Meningitis 030217 neurology & neurosurgery Encephalitis |
| Zdroj: | Frontiers in Immunology, Vol 11 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2020.612323/full |
| Popis: | BackgroundThere 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.MethodsData 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.ResultsWe 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.ConclusionThere 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 |
| Databáze: | OpenAIRE |
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