Helena Buso, Etai Adam, Peter D Arkwright, Sagar Bhattad, Amir Ali Hamidieh, Maryam Behfar, Alexandre Belot, Sarah Benezech, Alice Y Chan, Yanick J Crow, Christopher C Dvorak, Aisling M Flinn, Urvi Kapoor, Arjan Lankester, Masao Kobayashi, Risa Matsumura, Hadi Mottaghipisheh, Satoshi Okada, Marie Ouachee, Nima Parvaneh, Stalin Ramprakash, Prakash Satwani, Samin Sharafian, Clément Triaille, Robert F Wynn, Nasim Movahedi, Vahid Ziaee, Eleri Williams, Mary Slatter, Andrew R Gennery
{"title":"造血干细胞移植治疗 C1q 缺乏症:代表 EBMT 先天性错误工作组进行的一项研究。","authors":"Helena Buso, Etai Adam, Peter D Arkwright, Sagar Bhattad, Amir Ali Hamidieh, Maryam Behfar, Alexandre Belot, Sarah Benezech, Alice Y Chan, Yanick J Crow, Christopher C Dvorak, Aisling M Flinn, Urvi Kapoor, Arjan Lankester, Masao Kobayashi, Risa Matsumura, Hadi Mottaghipisheh, Satoshi Okada, Marie Ouachee, Nima Parvaneh, Stalin Ramprakash, Prakash Satwani, Samin Sharafian, Clément Triaille, Robert F Wynn, Nasim Movahedi, Vahid Ziaee, Eleri Williams, Mary Slatter, Andrew R Gennery","doi":"10.1007/s10875-024-01819-1","DOIUrl":null,"url":null,"abstract":"<p><p>C1q deficiency is a rare inborn error of immunity characterized by increased susceptibility to infections and autoimmune manifestations mimicking SLE, with an associated morbidity and mortality. Because C1q is synthesized by monocytes, to date, four patients treated with allogeneic HSCT have been reported, with a positive outcome in three. We conducted an international retrospective study to assess the outcome of HSCT in C1q deficiency. Eighteen patients, fourteen previously unreported, from eleven referral centres, were included. Two patients had two HSCTs, thus 20 HSCTs were performed in total, at a median age of 10 years (range 0.9-19). Indications for HSCT were autoimmune manifestations not controlled by ongoing treatment in seventeen, and early development of MALT lymphoma in one patient. Overall survival (OS) was 71% and event-free survival was 59% at two years (considering an event as acute GvHD ≥ grade III, disease recurrence and death). In eleven patients HSCT led to resolution of autoimmune features and discontinuation of immunosuppressive treatments (follow-up time range 3-84 months). Five patients died due to transplant-related complications. Patients with a severe autoimmune phenotype, defined as neurological and/or renal involvement, had the worst OS (40% vs 84%; p = 0.034). Reviewing data of 69 genetically confirmed C1q deficient patients, we found that anti-Ro antibodies are associated with neurologic involvement, and anti-RNP and anti-DNA antibodies with renal involvement. In conclusion, HSCT may be a valid curative option for C1q deficiency, but careful selection of patients, with an accurate assessment of risk and benefit, is mandatory.</p>","PeriodicalId":15531,"journal":{"name":"Journal of Clinical Immunology","volume":null,"pages":null},"PeriodicalIF":7.2000,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522153/pdf/","citationCount":"0","resultStr":"{\"title\":\"Hematopoietic Stem Cell Transplantation for C1q Deficiency: A Study on Behalf of the EBMT Inborn Errors Working Party.\",\"authors\":\"Helena Buso, Etai Adam, Peter D Arkwright, Sagar Bhattad, Amir Ali Hamidieh, Maryam Behfar, Alexandre Belot, Sarah Benezech, Alice Y Chan, Yanick J Crow, Christopher C Dvorak, Aisling M Flinn, Urvi Kapoor, Arjan Lankester, Masao Kobayashi, Risa Matsumura, Hadi Mottaghipisheh, Satoshi Okada, Marie Ouachee, Nima Parvaneh, Stalin Ramprakash, Prakash Satwani, Samin Sharafian, Clément Triaille, Robert F Wynn, Nasim Movahedi, Vahid Ziaee, Eleri Williams, Mary Slatter, Andrew R Gennery\",\"doi\":\"10.1007/s10875-024-01819-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>C1q deficiency is a rare inborn error of immunity characterized by increased susceptibility to infections and autoimmune manifestations mimicking SLE, with an associated morbidity and mortality. Because C1q is synthesized by monocytes, to date, four patients treated with allogeneic HSCT have been reported, with a positive outcome in three. We conducted an international retrospective study to assess the outcome of HSCT in C1q deficiency. Eighteen patients, fourteen previously unreported, from eleven referral centres, were included. Two patients had two HSCTs, thus 20 HSCTs were performed in total, at a median age of 10 years (range 0.9-19). Indications for HSCT were autoimmune manifestations not controlled by ongoing treatment in seventeen, and early development of MALT lymphoma in one patient. Overall survival (OS) was 71% and event-free survival was 59% at two years (considering an event as acute GvHD ≥ grade III, disease recurrence and death). In eleven patients HSCT led to resolution of autoimmune features and discontinuation of immunosuppressive treatments (follow-up time range 3-84 months). Five patients died due to transplant-related complications. Patients with a severe autoimmune phenotype, defined as neurological and/or renal involvement, had the worst OS (40% vs 84%; p = 0.034). Reviewing data of 69 genetically confirmed C1q deficient patients, we found that anti-Ro antibodies are associated with neurologic involvement, and anti-RNP and anti-DNA antibodies with renal involvement. In conclusion, HSCT may be a valid curative option for C1q deficiency, but careful selection of patients, with an accurate assessment of risk and benefit, is mandatory.</p>\",\"PeriodicalId\":15531,\"journal\":{\"name\":\"Journal of Clinical Immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":7.2000,\"publicationDate\":\"2024-10-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11522153/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Clinical Immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s10875-024-01819-1\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Clinical Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s10875-024-01819-1","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Hematopoietic Stem Cell Transplantation for C1q Deficiency: A Study on Behalf of the EBMT Inborn Errors Working Party.
C1q deficiency is a rare inborn error of immunity characterized by increased susceptibility to infections and autoimmune manifestations mimicking SLE, with an associated morbidity and mortality. Because C1q is synthesized by monocytes, to date, four patients treated with allogeneic HSCT have been reported, with a positive outcome in three. We conducted an international retrospective study to assess the outcome of HSCT in C1q deficiency. Eighteen patients, fourteen previously unreported, from eleven referral centres, were included. Two patients had two HSCTs, thus 20 HSCTs were performed in total, at a median age of 10 years (range 0.9-19). Indications for HSCT were autoimmune manifestations not controlled by ongoing treatment in seventeen, and early development of MALT lymphoma in one patient. Overall survival (OS) was 71% and event-free survival was 59% at two years (considering an event as acute GvHD ≥ grade III, disease recurrence and death). In eleven patients HSCT led to resolution of autoimmune features and discontinuation of immunosuppressive treatments (follow-up time range 3-84 months). Five patients died due to transplant-related complications. Patients with a severe autoimmune phenotype, defined as neurological and/or renal involvement, had the worst OS (40% vs 84%; p = 0.034). Reviewing data of 69 genetically confirmed C1q deficient patients, we found that anti-Ro antibodies are associated with neurologic involvement, and anti-RNP and anti-DNA antibodies with renal involvement. In conclusion, HSCT may be a valid curative option for C1q deficiency, but careful selection of patients, with an accurate assessment of risk and benefit, is mandatory.
期刊介绍:
The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.