Delayed Diagnosis and Complications of Predominantly Antibody Deficiencies in a Cohort of Australian Adults

Frontiers in Immunology

Joseph De Luca¹  Kymble Spriggs¹  Jo A. Douglass¹  Mittal Patel¹  Robyn E. O’Hehir²  Menno C. van Zelm²  Stephen Holdsworth³  Sara L. Barnes³  Samar Ojaimi³  Fiona Hore-Lacy⁴  Robert G. Stirling⁴  Julian J. Bosco⁴  Gary A. Unglik⁵  Priscilla Auyeung⁵  Jeremy McComish⁵  Yang Tran⁵  Katherine Nicholls⁵  Paul U. Cameron⁶  Philip D. Hodgkin⁷  Elizabeth Kruse⁷  Michael F. Sutherland⁹  Tran Binh Giang^1,10  Vanessa L. Bryant^1,11  Charlotte A. Slade^1,11 

[1] 0School of Medicine, The University of Melbourne, Melbourne, VIC, Australia;1Department of Immunology and Pathology, Central Clinical School, Monash University and Alfred Hospital, Melbourne, VIC, Australia;Department of Allergy and Immunology, Monash Medical Centre, Melbourne, VIC, Australia;Department of Allergy, Immunology and Respiratory Medicine, The Alfred Hospital, Melbourne, VIC, Australia;Department of Clinical Immunology and Allergy, The Royal Melbourne Hospital, Melbourne, VIC, Australia;Department of Infectious Diseases, Monash University and Alfred Hospital, Melbourne, VIC, Australia;Department of Medical Biology, The University of Melbourne, Melbourne, VIC, Australia;Department of Medicine, Monash Medical Centre, Melbourne, VIC, Australia;Department of Respiratory and Sleep Medicine, The Austin Hospital, Melbourne, VIC, Australia;Immunology Division, The Walter and Eliza Hall Institute for Medical Research, Melbourne, VIC, Australia;The Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies, Melbourne, VIC, Australia;

关键词: predominantly antibody deficiency;    primary immunodeficiency;    diagnostic delay;    common variable immunodeficiency;    X-linked agammaglobulinemia;    immunoglobulin subclass deficiency;   

DOI  :  10.3389/fimmu.2018.00694

来源: DOAJ

【 摘 要 】

BackgroundPredominantly antibody deficiencies (PADs) are the most common type of primary immunodeficiency in adults. PADs frequently pass undetected leading to delayed diagnosis, delayed treatment, and the potential for end-organ damage including bronchiectasis. In addition, PADs are frequently accompanied by comorbid autoimmune disease, and an increased risk of malignancy.ObjectivesTo characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia.MethodsWe identified adult patients receiving, or having previously received immunoglobulin replacement therapy for a PAD at four hospitals in metropolitan Melbourne, and retrospectively characterized their clinical and diagnostic features.Results179 patients from The Royal Melbourne, Alfred and Austin Hospitals, and Monash Medical Centre were included in the study with a median age of 49.7 years (range: 16–87 years), of whom 98 (54.7%) were female. The majority of patients (116; 64.8%) met diagnostic criteria for common variable immunodeficiency (CVID), and 21 (11.7%) were diagnosed with X-linked agammaglobulinemia (XLA). Unclassified hypogammaglobulinemia (HGG) was described in 22 patients (12.3%), IgG subclass deficiency (IGSCD) in 12 (6.7%), and specific antibody deficiency (SpAD) in 4 individuals (2.2%). The remaining four patients had a diagnosis of Good syndrome (thymoma with immunodeficiency). There was no significant difference between the age at diagnosis of the disorders, with the exception of XLA, with a median age at diagnosis of less than 1 year. The median age of reported symptom onset was 20 years for those with a diagnosis of CVID, with a median age at diagnosis of 35 years. CVID patients experienced significantly more non-infectious complications, such as autoimmune cytopenias and lymphoproliferative disease, than the other antibody deficiency disorders. The presence of non-infectious complications was associated with significantly reduced survival in the cohort.ConclusionOur data are largely consistent with the experience of other centers internationally, with clear areas for improvement, including reducing diagnostic delay for patients with PADs. It is likely that these challenges will be in part overcome by continued advances in implementation of genomic sequencing for diagnosis of PADs, and with that opportunities for targeted treatment of non-infectious complications.

【 授权许可】

Unknown