Rheumatology (Oxford, England) · 2026
Genetic landscape of early-onset systemic lupus erythematous in India.
СтатьяНаблюдательное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Sharma Madhubala, Pilania Rakesh Kumar, Volpi Stefano, Bocca Paola, Jindal Ankur, Vignesh Pandiarajan, Suri Deepti, Sharma Saniya, Dhaliwal Manpreet, Garg Ravinder, Kaur Gurjit, Saka Ruchi, Mamadpur Mahabaleshwar, Mahadevan Sabarinath, Haque Israrul, Ghosh Parasar, Reddy Mounika, Choudhary Abhijit, Arora Amit, Das Reena, Ahluwalia Jasmina, Gattorno Marco, Singh Surjit, Rawat Amit
Аннотация
OBJECTIVES: To investigate the genetic basis of early-onset systemic lupus erythematosus (EOSLE) in a large Indian pediatric SLE (pSLE) cohort.
METHOD: This prospective observational study investigated monogenic causes in 97 of 365 pSLE patients. Inclusion criteria for the study comprised patients with EOSLE (age ≤8 years) and/or those with a clinical suspicion of monogenic lupus. Monogenic cause was suspected in 97 patients. Genetic screening using targeted next-generation sequencing on the Ion S5 system in 55 of 97 patients [complement defect gene panel in 28 and type 1 interferonopathy gene Interferon (IFN)+ Adaptive Immunity panel in 27] was performed. The remaining 42 patients underwent whole-exome sequencing (WES).
RESULTS: Among 97 patients, 22 (22.68%; 11 boys and 11 girls) were found to carry pathogenic variants. Median symptom onset in monogenic cases was 2 years (range: 2 months to 9 years). Monogenic lupus was identified in both EOSLE and older children with strong clinical suspicion. EOSLE patients showed a higher diagnostic yield (28.4%) compared with older children (4.4%). Consanguinity was reported in 7/22 (31.8%) patients. Variants were found in C1QA (n = 7), C1QC (n = 2), C1QB (n = 1), C1R (n = 1), C3 (n = 2), ACP5 (n = 2), STING1, DNASE2, ADAR, TREX1, DNASE1L3, PEPD and SLC7A7 (each n = 1).
CONCLUSIONS: Monogenic causes were found in at least 6.1% of the overall cohort of pSLE and in 22.7% of genetically screened cases, with the highest yield in EOSLE (28.4%). C1QA was the most common single-gene defect (7.2%). These findings underscore the value of genetic testing in pSLE, especially those with EOSLE or suggestive clinical features.
METHOD: This prospective observational study investigated monogenic causes in 97 of 365 pSLE patients. Inclusion criteria for the study comprised patients with EOSLE (age ≤8 years) and/or those with a clinical suspicion of monogenic lupus. Monogenic cause was suspected in 97 patients. Genetic screening using targeted next-generation sequencing on the Ion S5 system in 55 of 97 patients [complement defect gene panel in 28 and type 1 interferonopathy gene Interferon (IFN)+ Adaptive Immunity panel in 27] was performed. The remaining 42 patients underwent whole-exome sequencing (WES).
RESULTS: Among 97 patients, 22 (22.68%; 11 boys and 11 girls) were found to carry pathogenic variants. Median symptom onset in monogenic cases was 2 years (range: 2 months to 9 years). Monogenic lupus was identified in both EOSLE and older children with strong clinical suspicion. EOSLE patients showed a higher diagnostic yield (28.4%) compared with older children (4.4%). Consanguinity was reported in 7/22 (31.8%) patients. Variants were found in C1QA (n = 7), C1QC (n = 2), C1QB (n = 1), C1R (n = 1), C3 (n = 2), ACP5 (n = 2), STING1, DNASE2, ADAR, TREX1, DNASE1L3, PEPD and SLC7A7 (each n = 1).
CONCLUSIONS: Monogenic causes were found in at least 6.1% of the overall cohort of pSLE and in 22.7% of genetically screened cases, with the highest yield in EOSLE (28.4%). C1QA was the most common single-gene defect (7.2%). These findings underscore the value of genetic testing in pSLE, especially those with EOSLE or suggestive clinical features.