Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Heterozygous SERPINA1 Defects and Their Impact on Clinical Manifestations of Patients with Predominantly Antibody Deficiencies

Styliani Sarrou
ORCID logo ,
Ioanna Voulgaridi
,
Athanasia Fousika
,
Katerina Dadouli
ORCID logo ,
Olympia Margaritopoulou
,
Ioannis Kakkas
,
Christos Hadjichristodoulou
,
Fani Kalala
,
Matthaios Speletas
* ORCID logo
Version 1 : Received: 28 March 2024 / Approved: 28 March 2024 / Online: 28 March 2024 (09:58:29 CET)

How to cite: Sarrou, S.; Voulgaridi, I.; Fousika, A.; Dadouli, K.; Margaritopoulou, O.; Kakkas, I.; Hadjichristodoulou, C.; Kalala, F.; Speletas, M. Heterozygous SERPINA1 Defects and Their Impact on Clinical Manifestations of Patients with Predominantly Antibody Deficiencies. Preprints 2024, 2024031753. https://doi.org/10.20944/preprints202403.1753.v1 Sarrou, S.; Voulgaridi, I.; Fousika, A.; Dadouli, K.; Margaritopoulou, O.; Kakkas, I.; Hadjichristodoulou, C.; Kalala, F.; Speletas, M. Heterozygous SERPINA1 Defects and Their Impact on Clinical Manifestations of Patients with Predominantly Antibody Deficiencies. Preprints 2024, 2024031753. https://doi.org/10.20944/preprints202403.1753.v1

Abstract

Patients with predominantly antibody deficiencies (PAD) display hypogammaglobulinemia with a high prevalence of infections, along with autoimmune manifestations, benign and malignant lymphoproliferation and granulomatous disease. It is noteworthy that PAD patients, even those with defects in the same causative genes display a variable clinical phenotype, suggesting that additional genetic polymorphisms, located in either immune-related or non-immune-related genes, may affect their clinical and laboratory phenotype. In this context, we analyzed 80 PAD patients, including 70 with common variable immunodeficiency (CVID) for SERPINA1 defects, in order to investigate their possible contribution to PAD clinical phenotype. Eight CVID patients carried heterozygous pathogenic SERPINA1 defects with normal alpha-1 antitrypsin levels. Interestingly, the presence of the Z allele (rs28929474) which was found in three patients, was significantly associated with liver disease; hepatic complications were also observed in patients carrying the p.Leu23Gln (rs1379209512) and the p.Phe76del (rs775982338) alleles. Conversely, no correlation of SERPINA1 defective variants with respiratory complications was observed, although patients with pathogenic variants exhibit a reduced probability of developing autoimmune diseases. Therefore, we recommend SERPINA1 genetic analysis in PAD, in order to identify patients with a higher risk for liver disease.

Keywords

Predominantly antibody deficiencies; common variable immunodeficiency; alpha-1-antitrypsin; SERPINA1; liver disease.

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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