Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults

Charlotte A. Slade, Julian J. Bosco, Tran Binh Giang, Elizabeth Kruse, Robert G. Stirling, Paul U. Cameron, Fiona Hore-Lacy, Michael F. Sutherland, Sara L. Barnes, Stephen Holdsworth, Samar Ojaimi, Gary A. Unglik, Joseph De Luca, Mittal Patel, Jeremy McComish, Kymble Spriggs, Yang Tran, Priscilla Auyeung, Katherine Nicholls, Robyn E. O'Hehir & 4 others Philip D. Hodgkin, Jo A. Douglass, Vanessa L. Bryant, Menno C. van Zelm

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4 Citations (Scopus)

Abstract

Background: Predominantly 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. Objectives: To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. Methods: We 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. Results: 179 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. Conclusion: Our 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.

Original languageEnglish
Article number694
Number of pages9
JournalFrontiers in Immunology
Volume9
Issue numberMAY
DOIs
Publication statusPublished - 14 May 2018

Keywords

  • Common variable immunodeficiency
  • Diagnostic delay
  • Immunoglobulin subclass deficiency
  • Predominantly antibody deficiency
  • Primary immunodeficiency
  • Specific antibody deficiency
  • X-linked agammaglobulinemia

Cite this

Slade, Charlotte A. ; Bosco, Julian J. ; Giang, Tran Binh ; Kruse, Elizabeth ; Stirling, Robert G. ; Cameron, Paul U. ; Hore-Lacy, Fiona ; Sutherland, Michael F. ; Barnes, Sara L. ; Holdsworth, Stephen ; Ojaimi, Samar ; Unglik, Gary A. ; De Luca, Joseph ; Patel, Mittal ; McComish, Jeremy ; Spriggs, Kymble ; Tran, Yang ; Auyeung, Priscilla ; Nicholls, Katherine ; O'Hehir, Robyn E. ; Hodgkin, Philip D. ; Douglass, Jo A. ; Bryant, Vanessa L. ; van Zelm, Menno C. / Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults. In: Frontiers in Immunology. 2018 ; Vol. 9, No. MAY.
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title = "Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults",
abstract = "Background: Predominantly 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. Objectives: To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. Methods: We 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. Results: 179 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. Conclusion: Our 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.",
keywords = "Common variable immunodeficiency, Diagnostic delay, Immunoglobulin subclass deficiency, Predominantly antibody deficiency, Primary immunodeficiency, Specific antibody deficiency, X-linked agammaglobulinemia",
author = "Slade, {Charlotte A.} and Bosco, {Julian J.} and Giang, {Tran Binh} and Elizabeth Kruse and Stirling, {Robert G.} and Cameron, {Paul U.} and Fiona Hore-Lacy and Sutherland, {Michael F.} and Barnes, {Sara L.} and Stephen Holdsworth and Samar Ojaimi and Unglik, {Gary A.} and {De Luca}, Joseph and Mittal Patel and Jeremy McComish and Kymble Spriggs and Yang Tran and Priscilla Auyeung and Katherine Nicholls and O'Hehir, {Robyn E.} and Hodgkin, {Philip D.} and Douglass, {Jo A.} and Bryant, {Vanessa L.} and {van Zelm}, {Menno C.}",
year = "2018",
month = "5",
day = "14",
doi = "10.3389/fimmu.2018.00694",
language = "English",
volume = "9",
journal = "Frontiers in Immunology",
issn = "1664-3224",
publisher = "Frontiers Media",
number = "MAY",

}

Slade, CA, Bosco, JJ, Giang, TB, Kruse, E, Stirling, RG, Cameron, PU, Hore-Lacy, F, Sutherland, MF, Barnes, SL, Holdsworth, S, Ojaimi, S, Unglik, GA, De Luca, J, Patel, M, McComish, J, Spriggs, K, Tran, Y, Auyeung, P, Nicholls, K, O'Hehir, RE, Hodgkin, PD, Douglass, JA, Bryant, VL & van Zelm, MC 2018, 'Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults', Frontiers in Immunology, vol. 9, no. MAY, 694. https://doi.org/10.3389/fimmu.2018.00694

Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults. / Slade, Charlotte A.; Bosco, Julian J.; Giang, Tran Binh; Kruse, Elizabeth; Stirling, Robert G.; Cameron, Paul U.; Hore-Lacy, Fiona; Sutherland, Michael F.; Barnes, Sara L.; Holdsworth, Stephen; Ojaimi, Samar; Unglik, Gary A.; De Luca, Joseph; Patel, Mittal; McComish, Jeremy; Spriggs, Kymble; Tran, Yang; Auyeung, Priscilla; Nicholls, Katherine; O'Hehir, Robyn E.; Hodgkin, Philip D.; Douglass, Jo A.; Bryant, Vanessa L.; van Zelm, Menno C.

In: Frontiers in Immunology, Vol. 9, No. MAY, 694, 14.05.2018.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults

AU - Slade, Charlotte A.

AU - Bosco, Julian J.

AU - Giang, Tran Binh

AU - Kruse, Elizabeth

AU - Stirling, Robert G.

AU - Cameron, Paul U.

AU - Hore-Lacy, Fiona

AU - Sutherland, Michael F.

AU - Barnes, Sara L.

AU - Holdsworth, Stephen

AU - Ojaimi, Samar

AU - Unglik, Gary A.

AU - De Luca, Joseph

AU - Patel, Mittal

AU - McComish, Jeremy

AU - Spriggs, Kymble

AU - Tran, Yang

AU - Auyeung, Priscilla

AU - Nicholls, Katherine

AU - O'Hehir, Robyn E.

AU - Hodgkin, Philip D.

AU - Douglass, Jo A.

AU - Bryant, Vanessa L.

AU - van Zelm, Menno C.

PY - 2018/5/14

Y1 - 2018/5/14

N2 - Background: Predominantly 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. Objectives: To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. Methods: We 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. Results: 179 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. Conclusion: Our 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.

AB - Background: Predominantly 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. Objectives: To characterize the diagnostic and clinical features of adult PAD patients in Victoria, Australia. Methods: We 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. Results: 179 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. Conclusion: Our 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.

KW - Common variable immunodeficiency

KW - Diagnostic delay

KW - Immunoglobulin subclass deficiency

KW - Predominantly antibody deficiency

KW - Primary immunodeficiency

KW - Specific antibody deficiency

KW - X-linked agammaglobulinemia

UR - http://www.scopus.com/inward/record.url?scp=85047014405&partnerID=8YFLogxK

U2 - 10.3389/fimmu.2018.00694

DO - 10.3389/fimmu.2018.00694

M3 - Article

VL - 9

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

IS - MAY

M1 - 694

ER -