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Comparison of Diagnostic Criteria for Common Variable Immunodeficiency Disorders (CVID) in the New Zealand CVID Cohort Study

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Abstract

Common variable immunodeficiency disorders (CVID) are the most frequent symptomatic primary immune deficiencies in adults and children. In addition to recurrent and severe infections, patients with CVID are susceptible to autoimmune and inflammatory complications. The aetiologies of these uncommon conditions are, by definition, unknown. When the causes of complex disorders are uncertain, diagnostic criteria may offer valuable guidance to the management of patients. Over the last two decades, there have been four sets of diagnostic criteria for CVID in use. The original 1999 European Society for Immunodeficiencies and Pan-American Society for Immunodeficiency (ESID/PAGID) criteria are less commonly used than the three newer criteria: Ameratunga et al (Clin Exp Immunol 174:203–211, 2013), ESID (J Allergy Clin Immunol Pract, 2019) and ICON (J Allergy Clin Immunol Pract 4:38–59, 2016) criteria. The primary aim of the present study was to compare the utility of diagnostic criteria in a well-characterised cohort of CVID patients. The New Zealand CVID cohort study (NZCS) commenced in 2006 and currently comprises one hundred and thirteen patients, which represents approximately 70% of all known CVID patients in NZ. Many patients have been on subcutaneous or intravenous (SCIG/IVIG) immunoglobulin treatment for decades. Patients were given a clinical diagnosis of CVID as most were diagnosed before the advent of newer diagnostic criteria. Application of the three commonly used CVID diagnostic criteria to the NZCS showed relative sensitivities as follows: Ameratunga et al (Clin Exp Immunol 174:203–211, 2013), possible and probable CVID, 88.7%; ESID (J Allergy Clin Immunol Pract, 2019), 48.3%; and ICON (J Allergy Clin Immunol Pract 4:38–59, 2016), 47.1%. These differences were mostly due to the low rates of diagnostic vaccination challenges in patients prior to commencing SCIG/IVIG treatment and mirror similar findings in CVID cohorts from Denmark and Finland. Application of the Ameratunga et al (Clin Exp Immunol 174:203–211, 2013) CVID diagnostic criteria to patients on SCIG/IVIG may obviate the need to stop treatment for vaccine studies, to confirm the diagnosis.

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Acknowledgements

This nation-wide study was approved by the multiregional ethics committee of the New Zealand Ministry of Health (MEC 06/10/134) and the Auckland District Health Board (ADHB) ethics committee (3435). Informed consent was required for this study. Consent to publish was part of the ethics approval and patient consent. RA conducted the study, S-TW checked the data, and HL and RS made editorial contributions to the manuscript. We thank our patients for participating in these studies for the benefit of others. We thank colleagues for referring patients to our studies. The original publications relevant to diagnostic criteria and NZ patients described in case reports are cited in this article. No data will be made available as it could identify individual patients.

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The authors received financial support from ASCIA, the A + Trust, and IDFNZ.

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Correspondence to Rohan Ameratunga.

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Ameratunga, R., Longhurst, H., Steele, R. et al. Comparison of Diagnostic Criteria for Common Variable Immunodeficiency Disorders (CVID) in the New Zealand CVID Cohort Study. Clinic Rev Allerg Immunol 61, 236–244 (2021). https://doi.org/10.1007/s12016-021-08860-7

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