Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy

Background: It is still uncertain if a dysregulated expression of activating Fc gamma receptors (FcγRs) is associated with the development of immunoglobulin A nephropathy (IgAN). Methods: RNA sequencing was used to determine the mRNA levels of type I FcγRs, which were then verified by quantitative r...

Full description

Bibliographic Details
Main Authors: Hongfen Li, Youxia Liu, Huyan Yu, Fanghao Wang, Junya Jia, Tiekun Yan, Shan Lin
Format: Article
Language:English
Published: SAGE Publishing 2022-06-01
Series:Therapeutic Advances in Chronic Disease
Online Access:https://doi.org/10.1177/20406223221106878
_version_ 1811237818044776448
author Hongfen Li
Youxia Liu
Huyan Yu
Fanghao Wang
Junya Jia
Tiekun Yan
Shan Lin
author_facet Hongfen Li
Youxia Liu
Huyan Yu
Fanghao Wang
Junya Jia
Tiekun Yan
Shan Lin
author_sort Hongfen Li
collection DOAJ
description Background: It is still uncertain if a dysregulated expression of activating Fc gamma receptors (FcγRs) is associated with the development of immunoglobulin A nephropathy (IgAN). Methods: RNA sequencing was used to determine the mRNA levels of type I FcγRs, which were then verified by quantitative reverse transcription–polymerase chain reaction (qRT-PCR). Commercial ELISA kits were used to detect plasma soluble FcγRIIIb (sFcγRIIIb). Results: We first examined the expression of FcγRs genes in 17 patients with IgAN and six healthy controls. The expression of FcγRIa, FcγRIb, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb was shown to be higher in IgAN patients. Even without statistical significance, there was a downward trend in FcγRIIb mRNA levels in IgAN. We observed that the expression levels of activating FcγR mRNAs were consistently higher in an independent set of 20 IgAN patients and 20 healthy controls, confirming the RNA-seq results. FcγRIIIb was the IgG receptor with the greatest difference in expression between the two groups (log 2 fold-change = 1.82). We observed a much higher percent of FcγRIIIb positive cells in IgAN by flow cytometry. Next, we measured plasma sFcRIIIb levels in 50 patients with IgAN and 50 healthy controls. The findings revealed that the mean sFcγRIIIb level in plasma in participants with IgAN was much higher than that of healthy controls. Increased sFcγRIIIb levels were associated with a substantial increase in body mass index (BMI), lipid levels, serum creatinine level, and a larger percentage of sclerosis compared with lower sFcRIIIb levels. Patients in the group with higher sFcγRIIIb levels were more likely to get glucocorticoid treatment. Conclusion: The results demonstrated that the mRNA levels of the activating Fc receptor of IgG were significantly increased in IgAN. Patients with higher plasma sFcγRIIIb levels may have had more severe illness than those with lower levels.
first_indexed 2024-04-12T12:29:46Z
format Article
id doaj.art-68184fed36304df8adfd8dd57e3ddd90
institution Directory Open Access Journal
issn 2040-6231
language English
last_indexed 2024-04-12T12:29:46Z
publishDate 2022-06-01
publisher SAGE Publishing
record_format Article
series Therapeutic Advances in Chronic Disease
spelling doaj.art-68184fed36304df8adfd8dd57e3ddd902022-12-22T03:33:03ZengSAGE PublishingTherapeutic Advances in Chronic Disease2040-62312022-06-011310.1177/20406223221106878Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathyHongfen LiYouxia LiuHuyan YuFanghao WangJunya JiaTiekun YanShan LinBackground: It is still uncertain if a dysregulated expression of activating Fc gamma receptors (FcγRs) is associated with the development of immunoglobulin A nephropathy (IgAN). Methods: RNA sequencing was used to determine the mRNA levels of type I FcγRs, which were then verified by quantitative reverse transcription–polymerase chain reaction (qRT-PCR). Commercial ELISA kits were used to detect plasma soluble FcγRIIIb (sFcγRIIIb). Results: We first examined the expression of FcγRs genes in 17 patients with IgAN and six healthy controls. The expression of FcγRIa, FcγRIb, FcγRIIa, FcγRIIc, FcγRIIIa, and FcγRIIIb was shown to be higher in IgAN patients. Even without statistical significance, there was a downward trend in FcγRIIb mRNA levels in IgAN. We observed that the expression levels of activating FcγR mRNAs were consistently higher in an independent set of 20 IgAN patients and 20 healthy controls, confirming the RNA-seq results. FcγRIIIb was the IgG receptor with the greatest difference in expression between the two groups (log 2 fold-change = 1.82). We observed a much higher percent of FcγRIIIb positive cells in IgAN by flow cytometry. Next, we measured plasma sFcRIIIb levels in 50 patients with IgAN and 50 healthy controls. The findings revealed that the mean sFcγRIIIb level in plasma in participants with IgAN was much higher than that of healthy controls. Increased sFcγRIIIb levels were associated with a substantial increase in body mass index (BMI), lipid levels, serum creatinine level, and a larger percentage of sclerosis compared with lower sFcRIIIb levels. Patients in the group with higher sFcγRIIIb levels were more likely to get glucocorticoid treatment. Conclusion: The results demonstrated that the mRNA levels of the activating Fc receptor of IgG were significantly increased in IgAN. Patients with higher plasma sFcγRIIIb levels may have had more severe illness than those with lower levels.https://doi.org/10.1177/20406223221106878
spellingShingle Hongfen Li
Youxia Liu
Huyan Yu
Fanghao Wang
Junya Jia
Tiekun Yan
Shan Lin
Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy
Therapeutic Advances in Chronic Disease
title Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy
title_full Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy
title_fullStr Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy
title_full_unstemmed Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy
title_short Elevated activating Fc gamma receptors levels correlated with susceptibility and severity of IgA nephropathy
title_sort elevated activating fc gamma receptors levels correlated with susceptibility and severity of iga nephropathy
url https://doi.org/10.1177/20406223221106878
work_keys_str_mv AT hongfenli elevatedactivatingfcgammareceptorslevelscorrelatedwithsusceptibilityandseverityofiganephropathy
AT youxialiu elevatedactivatingfcgammareceptorslevelscorrelatedwithsusceptibilityandseverityofiganephropathy
AT huyanyu elevatedactivatingfcgammareceptorslevelscorrelatedwithsusceptibilityandseverityofiganephropathy
AT fanghaowang elevatedactivatingfcgammareceptorslevelscorrelatedwithsusceptibilityandseverityofiganephropathy
AT junyajia elevatedactivatingfcgammareceptorslevelscorrelatedwithsusceptibilityandseverityofiganephropathy
AT tiekunyan elevatedactivatingfcgammareceptorslevelscorrelatedwithsusceptibilityandseverityofiganephropathy
AT shanlin elevatedactivatingfcgammareceptorslevelscorrelatedwithsusceptibilityandseverityofiganephropathy