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Immunological and Clinical Phenotyping in Primary Antibody Deficiencies: a Growing Disease Spectrum

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Abstract

Purpose

Although common variable immunodeficiency (CVID) is considered the most prevalent symptomatic primary antibody deficiency (PAD), there is a population with symptomatic PADs that do not meet criteria for CVID. We analyzed clinical and immunological profiles of patients with different PADs to better understand the differences and similarities between CVID and other PADs.

Methods

We extracted clinical and laboratory data of patients with PADs from electronic medical records. Patients were categorized into CVID, IgG subclass 2 deficiency (IgG2D), IgG deficiency (IgGD), and specific antibody deficiency (sAbD) based on basal immunoglobulin levels and pneumococcal vaccine responses. We compared clinical and immunological characteristics in these groups.

Results

All patients, regardless of PAD types, showed similar frequencies of infections, bronchiectasis, and interstitial lung disease (ILD). Hematopoietic malignancies were more frequently found in the CVID than in the IgG2D, IgGD, and sAbD groups, while the latter groups trended towards an increased frequency of connective tissue diseases (CTD). Low counts of natural killer (NK) cells were associated with malignancy, autoimmunity, and ILD in CVID but not in other PAD groups.

Conclusions

Higher frequency of hematopoietic malignancy in CVID than in the other PADs and association of lower NK cell counts with non-infectious complications in CVID suggest a relationship between immune alterations and the development of non-infectious manifestations in PADs.

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Acknowledgments

We thank Caitlin Partridge in the Joint Data Analytics Team of the Yale Center for Clinical Investigation for her assistance in collecting data from electronic medical records. We also thank Dr. Veronika Shabanova for her advice on statistical analysis.

Authorship Contributions

J.J.S., D.L. and S.S. performed the chart review; J.J.S., C.P. and I.K. designed the study; J.J.S., D.L., S.S., J.L., E.J.C., C.P. and I.K. analyzed and interpreted the results; J.J.S., D.L., S.S., R.S., F.I.H., and I.K. participated in writing the manuscript; and I.K. supervised the research.

Funding

This work was supported in part by grants from the National Institutes of Health (R01AG056728 and R01AG055362 to IK).

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Author notes

  1. Daniel Liauw and Sabrina Siddiqui contributed equally to this work.

Authors and Affiliations

  1. Section of Rheumatology, Allergy and Immunology, Department of Internal Medicine, Yale University School of Medicine, 300 Cedar Street, New Haven, CT, 06520, USA

    Junghee J. Shin, Daniel Liauw, Sabrina Siddiqui, Juhyeon Lee, Eun Jae Chung, Ryan Steele, Florence Ida Hsu, Christina Price & Insoo Kang

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  1. Junghee J. Shin
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Correspondence to Insoo Kang.

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Shin, J.J., Liauw, D., Siddiqui, S. et al. Immunological and Clinical Phenotyping in Primary Antibody Deficiencies: a Growing Disease Spectrum. J Clin Immunol 40, 592–601 (2020). https://doi.org/10.1007/s10875-020-00773-y

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