TY - JOUR
T1 - Seeking Relevant Biomarkers in Common Variable Immunodeficiency
AU - Ho, Hsi En
AU - Cunningham-Rundles, Charlotte
N1 - Funding Information:
The authors thank the following clinical staff of the Mount Sinai Immunodeficiency Clinic: Cynthia Medina, Sandy Leon, Monica Reiter-Wong, Aurora Barriga, Nadine Bristol, and Elina Petrosyan.
Funding Information:
This work was partially supported by the National Institutes of Health and National Institute of Allergy and Infectious Diseases grants AI-061093, and AI-08603.
Publisher Copyright:
Copyright © 2022 Ho and Cunningham-Rundles.
PY - 2022/3/11
Y1 - 2022/3/11
N2 - Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency. More than 50% of patients in some series suffer from autoimmune or inflammatory complications (the “CVID+” phenotype), and these are not adequately addressed by current treatments. Despite major advancements in genetics, the pathogenesis of the CVID+ phenotype has remained unexplained for most patients, necessitating the need for relevant biomarkers in both the clinic and research settings. In the clinics, reduced isotype-switched memory B cells (≤ 0.55% of B cells) and reduced T cells (CD4) can be utilized to identify those with increased complication risks. Additionally, condition-specific markers have also been suggested for lymphoma (normal or elevated IgM) and progressive interstitial lung disease (increased BAFF, normal or elevated IgM). Additional biomarkers have provided insights into disease pathogenesis, demonstrating wider systemic inflammation (increased LBP, sCD14, and sCD25; expanded ILC3), mucosal defects (increased zonulin, I-FABP), and perhaps reduced anti-inflammatory capability (reduced HDL) in CVID. Most recently, efforts have revealed elevated circulating bioactive bacterial DNA levels – marking microbial translocation and potentially linking the causation of multiple inflammatory changes previously observed in CVID. The implementation of high throughput profiling techniques may accelerate the search of relevant biomarker profiles in CVID and lead to better clinical risk stratification, revealing disease insights, and identifying potential therapeutic targets.
AB - Common variable immunodeficiency (CVID) is the most common symptomatic form of primary immunodeficiency. More than 50% of patients in some series suffer from autoimmune or inflammatory complications (the “CVID+” phenotype), and these are not adequately addressed by current treatments. Despite major advancements in genetics, the pathogenesis of the CVID+ phenotype has remained unexplained for most patients, necessitating the need for relevant biomarkers in both the clinic and research settings. In the clinics, reduced isotype-switched memory B cells (≤ 0.55% of B cells) and reduced T cells (CD4) can be utilized to identify those with increased complication risks. Additionally, condition-specific markers have also been suggested for lymphoma (normal or elevated IgM) and progressive interstitial lung disease (increased BAFF, normal or elevated IgM). Additional biomarkers have provided insights into disease pathogenesis, demonstrating wider systemic inflammation (increased LBP, sCD14, and sCD25; expanded ILC3), mucosal defects (increased zonulin, I-FABP), and perhaps reduced anti-inflammatory capability (reduced HDL) in CVID. Most recently, efforts have revealed elevated circulating bioactive bacterial DNA levels – marking microbial translocation and potentially linking the causation of multiple inflammatory changes previously observed in CVID. The implementation of high throughput profiling techniques may accelerate the search of relevant biomarker profiles in CVID and lead to better clinical risk stratification, revealing disease insights, and identifying potential therapeutic targets.
KW - biomarkers
KW - common variable immunodeficiency
KW - complications
KW - environment
KW - genes
KW - pathogenesis
KW - primary immunodeficiency
UR - http://www.scopus.com/inward/record.url?scp=85127383607&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2022.857050
DO - 10.3389/fimmu.2022.857050
M3 - Review article
C2 - 35359997
AN - SCOPUS:85127383607
SN - 1664-3224
VL - 13
JO - Frontiers in Immunology
JF - Frontiers in Immunology
M1 - 857050
ER -